tag:theconversation.com,2011:/africa/topics/pain-series-2018-55420/articlesPain series 2018 – The Conversation2018-07-23T10:22:21Ztag:theconversation.com,2011:article/995572018-07-23T10:22:21Z2018-07-23T10:22:21ZWhy do paper cuts hurt so much?<figure><img src="https://images.theconversation.com/files/228268/original/file-20180718-142414-dso6zy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A boy with a paper cut.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/smiling-boy-bandaged-finger-211465750?src=M5v1AthJoiqzmhQ-7t1vKw-1-53">Suzanne Tucker/Shutterstock.com</a></span></figcaption></figure><p><a href="https://theconversation.com/por-que-duelen-tanto-las-cortadas-con-papel-100863"><em>Leer en español</em></a>.</p>
<p>Consider, for a moment, the paper cut. It happens suddenly and entirely unexpectedly, usually just as you are finally getting somewhere on that task you had been putting off.</p>
<p>Recall your sense of relief to finish that thank-you note to your aunt for the lovely sweater she sent you three months prior when, at the crucial moment, your hands failed you in their familiar task and the paper’s edge slid past its restraints into the flesh. Then pain – sharp, pure pain that bends your consciousness to the Only. Thing. That. Matters. Right. Now. There is sometimes a moment, between awareness and pain, when you bargain with fate, hoping that what just happened didn’t. But the hand is gone and the blood needs tending. </p>
<p>Physically, paper cuts hurt as much as they do for a variety of reasons. They typically occur on parts of our bodies that are the most sensitive, such as the fingers, lips or tongue. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143958/">The nerve networks</a> of these body parts can discriminate with exceptional clarity and specificity, sensations of pressure, heat, cold and injury. Our brains even have specialized areas to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778751/">receive signals</a> coming from these parts in high definition. The exquisite sensing abilities that makes our fingers, lips and tongue so good at what they normally do, also makes injuries all the more painful.</p>
<p>These same highly sensitive areas are also parts we use all the time. Cuts on fingers, lips and the tongue tend to reopen throughout day dooming us to relive the pain again and again. Finally, the depth of the wound is perfect for exposing and exciting the nerve fibers of the skin without damaging them the way a deeper, more destructive injury can severely damage the nerve fibers impairing their ability to communicate pain. With a paper cut, the nerve fibers are lit, and they are fully operational. </p>
<h2>How to stop the ouch</h2>
<p>As a <a href="https://www.theabfm.org/public/whatisfamilymedicine.aspx">family physician</a>, <a href="https://medicine.tamhsc.edu/fmr/faculty/gabriel-neal.html">I</a> can recommend a few practical ways to minimize the discomfort of a paper cut. First, wash the cut as soon as you can with soap and water. This will reduce the chance of infection and help the wound heal quickly. Keep the wound clean, and if possible, for a few days cover it with a small bandage to cushion the wound and limit reopening. </p>
<p>While the physical effects of a paper cut are a real drag, I am fascinated by the mental and emotional response to the paper cut. While both intentional self-injury (example: cutting) and major accidental injury (example: car accident with loss of limb or paralysis) have inspired important, ongoing research into their psychological effects, minor accidental injuries do not – and that is OK. There are more pressing issues in need of research than paper cuts. </p>
<p>But for a moment think back to the feelings you may have had about your paper cuts: surprise that the mundane act of licking an envelope could result in an injury (and so much blood!); shame that your body didn’t coordinate such a simple task (why does this always happen to me?); anger for hurting yourself (arrrgh!); anxiety that it will happen again (I still have 200 more envelopes to go!). Paper cuts are trivial, but they may invoke a complex emotional response.</p>
<p>Paper cuts remind us that no matter how many times we have performed even a simple task we are capable of accidentally hurting ourselves. If that makes us a little more sympathetic to our neighbor’s pains, and a little more humble, then maybe paper cuts do us some good too. Maybe.</p><img src="https://counter.theconversation.com/content/99557/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gabriel Neal does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Ouch! Who hasn’t felt the effects of a paper cut and then cursed the gods or themselves for the injury? But have you ever wondered why they hurt so much? A professor of family medicine explains why.Gabriel Neal, Clinical Associate Professor of Family Medicine, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/968822018-06-27T10:43:28Z2018-06-27T10:43:28ZHow opioid addiction alters our brains to always want more<figure><img src="https://images.theconversation.com/files/224280/original/file-20180621-137717-a81u4p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The way opioids work on the brain makes finding non-opioid treatments for addiction very challenging.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Washington-Opioids/73792f4373aa4ef29f43f1745c60ae28/1/0">AP Photo/Ted S. Warren</a></span></figcaption></figure><p>At a hearing on Capitol Hill earlier this year, U.S. Senator Lamar Alexander <a href="https://www.c-span.org/video/?445683-1/nih-leaders-testify-2019-budget-request">asked an important question</a>: Why is most of the treatment for opioid addiction more opioids? </p>
<p>In response, Nora Volkow, director of the National Institute on Drug Abuse, and Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, did their best to assure the senator – and thus the nation – that scientists are hard at work developing treatments for addicts that are not just more of the same. </p>
<p>But even with a number of research projects to <a href="https://theconversation.com/opioids-dont-have-to-be-addictive-the-new-versions-will-treat-pain-without-triggering-pleasure-97593">develop alternatives to opioids</a>, the reality is that our brains don’t let go of an opioid addiction easily, if at all. </p>
<p>It’s not just that your brain likes opioids – whether it’s prescription pain relievers, heroin or synthetic opioids such as fentanyl – and responds to them with feelings of euphoria and warmth, helping you overcome pain. Opioids disrupt the normal functioning of your brain, making it harder for people to quit and more vulnerable to relapse. </p>
<h2>Hacking the human brain</h2>
<p>The hopeful news regarding the opioid crisis is that scientists are searching for promising targets in developing non-opioid treatments for addiction. For example, this year a <a href="https://www.medpagetoday.com/publichealthpolicy/opioids/72026">Food and Drug Administration advisory committee voted to approve the high blood pressure medicine lofexidine</a> as the first non-opioid medication to treat opioid withdrawal symptoms. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=402&fit=crop&dpr=1 600w, https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=402&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=402&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=506&fit=crop&dpr=1 754w, https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=506&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/224285/original/file-20180621-137708-rt4mvz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=506&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The opioid crisis stems from use of both prescription pain relievers and illicit drugs that work on the brain the same way by treating pain and producing euphoria.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Opioid-Memorial-Wall/22fd05524647415ab4f8d4da1c68239e/301/0">AP Photo/Keith Srakocic</a></span>
</figcaption>
</figure>
<p>But in order to accomplish the feat of producing something that looks like a long-term answer to opioid addiction, scientists will have to hack the science of the human brain. Earlier this year, the NIH launched an initiative called Helping to End Addiction Long-term (<a href="https://jamanetwork.com/journals/jama/fullarticle/2684941">HEAL</a>) that takes an important step forward in doing just that. It funds research into potential new treatments aimed at <a href="https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative/heal-initiative-research-plan">the brain reward pathway</a> – the regions of the brain where neurons release the neurotransmitter dopamine, which gives you a jolt of pleasure, makes you feel good and signals you to repeat this pleasurable behavior in the future. By developing these opioid alternatives, the strategy is to prevent opioid abuse, dependence and relapse. </p>
<p>For now, though, we are a nation caught in a vicious cycle. The most common drugs prescribed to treat opioid addiction are methadone and buprenorphine, which bind to the same mu (µ) brain receptors as the illicit forms of the drug. </p>
<p>Methadone is an agonist, meaning it binds to the mu opioid receptors and its long-acting function satisfies an addict’s craving for heroin without causing the intense high of the illicit form of opioids. <a href="https://www.naabt.org/faq_answers.cfm?ID=2">Buprenorphine</a> also acts on the mu opioid receptor, but unlike methadone or heroin, it is a partial agonist that lessens the painful symptoms of withdrawal while producing a limited version of the euphoric effects of opioid drugs. At the correct dose, buprenorphine can suppress cravings and withdrawal symptoms and block the effects of other opioids, giving time to recondition the brain and <a href="https://www.nytimes.com/2018/06/23/health/opioid-addiction-suboxone-treatment.html">learn coping mechanisms</a> for the social and emotional aspects of addiction.</p>
<p>While treating opioid addiction with more opioids isn’t ideal, addicts who don’t receive those medicines and are treated with only psychological support are <a href="https://www.psychologytoday.com/us/blog/when-your-adult-child-breaks-your-heart/201802/best-practices-treating-opiate-addiction">twice as likely to die of a relapse overdose</a>.</p>
<p>The most commonly known non-opioid treatment for opioid addiction is naltrexone, sold under the brand names Vivitrol and ReVia. Naltrexone binds to opioid receptors and blocks the pain relief and euphoric effect of opioids – but it’s not a cure-all. Studies have reported large numbers of dropouts from treatment because addicts can’t begin using naltrexone <a href="https://www.vivitrol.com/opioid-alcohol-addiction-awareness?s_mcid=ppc-google-Branded-Vivitrol-General-Terms-naltrexone&s_mcid=ppc-google-vivitrol-general-terms">until they are no longer experiencing the physical withdrawal symptoms from opioids</a>. Many never get to that point. </p>
<h2>How opioids rewire the brain</h2>
<p>What is it that makes the brain so vulnerable to opioid drugs as opposed to other drugs of abuse? </p>
<p>It has been found that opioids readily cross the <a href="https://faculty.washington.edu/chudler/bbb.html">blood-brain barrier</a>, which is composed of tightly packed cells that line blood vessels and keep most molecules out of the brain. This is what makes the effect of opioids incredibly potent, <a href="https://www.ncbi.nlm.nih.gov/pubmed/29731678">giving the user a feeling of “instant reward.”</a> </p>
<p>Over time, use of opioids also triggers changes in the physiology of the brain by altering reward processing, disrupting neural connections and ultimately decreasing brain volume. Scientists know that µ-opioid receptors (MORs) are quite prevalent in cells in the hippocampus, the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138838/">brain region responsible for learning and memory</a>. Opioids seem to have a robust impact on learning and memory, ultimately making the addiction more powerful and creating another strong hold on the brain. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=362&fit=crop&dpr=1 600w, https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=362&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=362&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=454&fit=crop&dpr=1 754w, https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=454&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/224564/original/file-20180624-26579-h8lzhy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=454&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The sharpest rise in overdoses in recent years has been from people who took synthetic opioids.</span>
<span class="attribution"><a class="source" href="https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates">Centers for Disease Control and Prevention</a></span>
</figcaption>
</figure>
<p>Additionally, researchers have found that opioids alter neural reward processing. The amygdala – the emotional and reward-processing center of the brain – is governed by the prefrontal cortex or the “logic center.” Neural connections from the amygdala project signals to the prefrontal cortex – so when humans have an initial impulse, our executive function or “higher thinking” kicks in to regulate our emotional and reward-seeking behavior. </p>
<p>Opioids disrupt this process and the reward-seeking behavior begins to dominate. Opioid addicts are known to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921346/">lose gray matter in the amygdala</a>, which drives drug craving and dependence. Opioids can further cause areas of the cortex to lose volume, and these changes have been found to persist even after drug use ceases. This suggests that brains lose neuroplasticity – <a href="https://www.ncbi.nlm.nih.gov/pubmed/29183383">the brain’s way of repairing itself</a>.</p>
<p>The result of these changes to brain chemistry is that people are wired to respond to opioids and crave them at increasingly higher levels as long as they are used. That’s one reason why heroin deaths have surged more than five-fold since 2010, the Drug Enforcement Administration <a href="https://www.dea.gov/pr/speeches-testimony/2018t/050818t.pdf">reports</a>. Users increasingly seek more extreme forms of the drug cut with fentanyl or its analogues – <a href="https://docs.house.gov/meetings/IF/IF00/20171025/106533/HHRG-115-IF00-Wstate-DohertyN-20171025.pdf">a form the DEA refers to as “hot” heroin for its increasing potency.</a></p>
<h2>Beyond treating addiction</h2>
<p>As fast and as furious as the opioid epidemic has come upon us, our nation should brace itself for potentially investing billions of dollars over decades to come to develop safer and more effective treatments, as well as ones that will address the complex brain damage opioids cause. </p>
<p>Given that the human brain remains very much a frontier for scientific discovery, what scientists learn through this research may have beneficial applications far beyond treating addiction. That might be the only hopeful outcome from this national tragedy.</p><img src="https://counter.theconversation.com/content/96882/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Two neuroscientists explain the cruel chemistry of opioid addiction and why this crisis could last a lifetime.Paul R. Sanberg, Senior Vice President for Research, Innovation & Knowledge Enterprise, University of South FloridaSamantha Portis, Doctoral candidate, medical sciences (neuroscience), University of South FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/979102018-06-26T10:40:31Z2018-06-26T10:40:31ZTreating pain in children can teach us about treating pain in adults<figure><img src="https://images.theconversation.com/files/223645/original/file-20180618-85863-11jpobl.png?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Instructor Sensei Giuseppe of Kids Kicking Cancer Italy, teaching a young cancer patient in Bergamo, Italy, on June 6, 2018. </span> <span class="attribution"><span class="source">Elimelech Goldberg/Kids Kicking Cancer Italy </span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>The U.S. government declared a national <a href="https://www.hhs.gov/about/news/2017/10/26/hhs-acting-secretary-declares-public-health-emergency-address-national-opioid-crisis.html">public health emergency</a> in October 2017 to address the opioid addiction crisis. More than six months later, the country is still in the throes of the crisis, with no sight in end.</p>
<p>With the nation’s spotlight on addiction to pain medications, the underlying epidemic of chronic or severe pain goes largely ignored. Further, although it’s hard to know how people are treating their pain, <a href="https://insights.ovid.com/pubmed?pmid=21397401">survey data</a> indicate that a third are on prescription pain medications. Indeed, more than 100 million U.S. adults are living with some form of chronic or severe <a href="https://www.nap.edu/read/13172/chapter/2#1">pain</a>. This is more than the number of people living with diabetes, heart disease or cancer, combined. </p>
<p>Almost half are not getting the pain relief needed from medications, and many pain medications have side effects ranging from constipation, nausea and vomiting to addiction and overdose. Many are seeking alternative approaches to pain management. Some surprising answers may come from a group of kids with cancer. </p>
<p>I’m a <a href="https://scholar.google.com/citations?user=S9ykvZUAAAAJ&hl=en">neuroscientist</a> who studies the adverse effects of <a href="https://tnp2lab.org/">painful experiences in children</a>, and we are finding that kids may be able to change the wiring of pain systems in the brain – without medications. </p>
<h2>Pain in childhood cancer</h2>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223922/original/file-20180619-126531-1o0ii1y.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Two girls with cancer, displaying some of the side effects of cancer treatment such as hair loss, exhibit their resilience.</span>
<span class="attribution"><a class="source" href="https://visualsonline.cancer.gov/details.cfm?imageid=2191">Bill Branson/National Cancer Institute</a></span>
</figcaption>
</figure>
<p>The emotional toll of childhood cancer is so unbearable that it is sometimes easy to overlook that extreme physical pain that children with cancer undergo. The “cure” for childhood cancer includes invasive and sometimes painful treatment procedures, including venipunctures (blood draws), port-starts, spinal taps and bone marrow aspirations, which is a procedure that involves taking a sample with a syringe from the spongy tissue found inside bones. On top of that, chemotherapy can cause painful neuropathy, nausea and diarrhea, in addition to pain caused by the tumor itself. </p>
<p>Although pain is often under-recognized in children, those who treat this population see this pain every day and thus make treating children’s pain a top priority. As a result, novel pain treatments sometimes first emerge to treat kids. </p>
<p>The perception of pain happens in the brain, in regions of the so-called <a href="https://academic.oup.com/brain/article/122/9/1765/321835">pain matrix</a>, including the anterior cingulate cortex, thalamus and insula. These brain regions are involved in a wide range of cognitive and emotion-related processes, and critically, seem to be involved with why pain feels so bad, or what is called the affective aspects of pain. Importantly, regions of the pain matrix continue to develop throughout childhood, making them especially sensitive to repeated pain exposures. So the frequent pain experienced with childhood cancer and cancer-related treatment procedures early in life may be especially harmful to the <a href="https://price.ctsi.ufl.edu/files/2014/04/ejn12414.pdf">developing nervous system</a>. </p>
<p>In some of the <a href="https://link.springer.com/article/10.1007/s11065-017-9365-1">research studies</a> conducted by our group and others, we have found that childhood cancer affects the functioning of the pain matrix. Changes in brain structure and function may contribute to chronic pain and other <a href="https://www.nature.com/articles/nrc3634">long-term or “late” effects</a> commonly reported by childhood cancer patients and survivors, such as memory and attentional problems. </p>
<p>Given the potential for negative effects on the developing brain, the media attention about the opioid epidemic, and the fact that in some cases, children are already receiving thousands of pills over the course of their cancer treatment, physicians need alternative non-pharmacological approaches to pain management to address pediatric cancer pain.</p>
<h2>New answers to pain?</h2>
<p>One such promising approach is <a href="https://kidskickingcancer.org/">Kids Kicking Cancer</a>, a nonprofit organization that is now in five different countries and using martial arts techniques to empower children beyond the pain, distress and uncertainty of their disease. The therapy of Kids Kicking Cancer involves a variety of mind-body interventions that are science-based, including mindfulness, meditation, breathing and visualization. </p>
<p>In a recent <a href="https://www.dovepress.com/martial-arts-intervention-decreases-pain-scores-in-children-with-malig-peer-reviewed-article-PHMT">study</a>, colleagues in my research group demonstrated that Kids Kicking Cancer is an effective intervention for reducing pediatric cancer pain, with nearly 90 percent of children reporting a reduction in pain by an average of 40 percent over the course of a one-hour session. Few if any pain medications of any kind have demonstrated such dramatic results.</p>
<p>Now, our lab at Wayne State University is using brain imaging to study how this works. Although the study is still underway, some of our preliminary results suggest that children with cancer are able to use these techniques to take control of their lives and rewire their brain’s pain matrix. </p>
<p>These techniques may work by not getting rid of the pain signals coming in to the brain, but rather, by changing how distracting or ‘salient’ the brain sees them. In other words, these techniques may help to control pain by turning down its volume control - pain is just some of the many signals in the brain and people don’t have to pay attention to it. And, importantly, these techniques appear to bypass the opioid receptors in the brain.</p>
<p>We adults may have a lot to learn from these children. One of the most unusual elements of Kids Kicking Cancer is that the children with cancer become the teachers. Indeed, the Kids Kicking Cancer “Heroes Circle” program allows for the children to show adults and other children how to <a href="https://www.amazon.com/Perfect-Created-Imperfect-World-Perfectly/dp/0986358320">“breathe in the light and blow out the darkness”</a> of stress, anger and pain. Our research group hosted a Kids Kicking Cancer seminar with adults and found that almost 100 percent of participants – <a href="https://www.amazon.com/Perfect-Created-Imperfect-World-Perfectly/dp/0986358320">97 percent</a>, to be precise – reported that the seminar had a “profound impact” on their lives.</p>
<p>In this seminar, they learned from children battling cancer that the “Breath Brake” can be used to help them overcome challenging stress. By integrating these techniques into their own lives, they can lower their own stress and anxiety but also help to reduce pain and suffering of the children. Thus, these age-old mind-body techniques – combined with a platform that provides a purpose to look beyond themselves to others for inspiration - may be a powerful underutilized therapeutic tool to help adults suffering from pain, addiction or trauma.</p>
<p>In partnership with the state of Michigan and the Wayne State University methadone clinic, we are now testing whether the Kids Kicking Cancer Heroes Circle <a href="https://www.amazon.com/Perfect-Created-Imperfect-World-Perfectly/dp/0986358304/">program</a> can reduce pain among adults addicted to opioids and whether the brain systems underlying pain and addiction can be rewired. The therapy is simple, and involves <a href="https://kidskickingcancer.org/the-breath-brake/breathing-exercises/">breathing</a> and guided imagery, such as using visualization to extract pain by “making holes” through the pain.</p>
<p>The first recommendation in the CDC’s <a href="https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm">guidelines</a> for doctors for treating chronic pain was to try non-pharmacological, non-opioid interventions first. So maybe we should look to some of our nation’s young superheroes who are battling cancer for some answers to address the epidemic of pain and addiction.</p><img src="https://counter.theconversation.com/content/97910/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hilary A. Marusak receives funding from the American Cancer Society and the St. Baldrick's Foundation. </span></em></p>Children with cancer often experience terrible pain. Adults who treat them are determined to lessen their suffering. Can the lessons from helping kids with cancer pain inform treatment for adults in pain?Hilary A. Marusak, Postdoctoral research fellow, Wayne State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/921692018-06-22T10:30:12Z2018-06-22T10:30:12ZPhysical therapy could lower need for opioids, but lack of money and time are hurdles<figure><img src="https://images.theconversation.com/files/223647/original/file-20180618-85825-3o79th.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Physical therapists Steven Hunter and Laura Hayes teach an unidentified patient lumbar stabilization exercises at the Equal Access Clinic in Gainesville, Florida</span> <span class="attribution"><span class="source">Maria Belen Farias, UF Health Photography</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Physical therapists help people walk again after a stroke and recover after injury or surgery, but did you know they also prevent exposure to <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393575/">opioids</a>? This is timely, given we are in a <a href="https://www.whitehouse.gov/briefings-statements/president-donald-j-trump-taking-action-drug-addiction-opioid-crisis/">public health emergency</a> related to an opioid crisis.</p>
<p>Many people addicted to opioids are <a href="https://www.drugabuse.gov/publications/research-reports/relationship-between-prescription-drug-heroin-abuse/prescription-opioid-use-risk-factor-heroin-use">first exposed</a> through a medical prescription for pain. Opiate-based drugs provide relief for acute conditions, such as post-surgical pain. </p>
<p>Unfortunately, the effectiveness of opioids decreases after time, requiring <a href="https://www.ncbi.nlm.nih.gov/pubmed/29796831">higher doses of the drug for the same effects</a> and, perhaps counter-intuitively, <a href="https://www.ncbi.nlm.nih.gov/pubmed/29796831">worsening pain in some people</a>. Many people progress from this prescription to other opiate derivatives, including heroin and fentanyl. As a result, a growing emphasis has been placed on nonpharmacological alternatives to opioids.</p>
<p>I am a physical therapist and I have studied non-pharmacological methods of preventing the transition from acute to chronic pain. It’s an exciting time for the field, because practice and research are showing that physical therapy could diminish the need for opioids, and thus lower the risk of addiction.</p>
<h2>Reducing initial exposures to opioids</h2>
<p>Part of the proposed solution to the opioid crisis is to limit new opioid exposures. Physical therapists are an important part of this process. And it is not just physical therapists who are saying this. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223651/original/file-20180618-85834-bvx501.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Mindy Miller/University of Florida Photography</span>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>A <a href="https://www.whitehouse.gov/sites/whitehouse.gov/files/images/Final_Report_Draft_11-1-2017.pdf">letter to the president</a> from the Commission on Combating Drug Addiction and the Opioid Crisis stated, “individuals with acute or chronic pain must have access to non-opioid pain management options. Everything from physical therapy, to non-opioid medications, should be easily accessible as an alternative to opioids.” U.S. Surgeon General Jerome Adams echoed this <a href="http://www.arkansasonline.com/news/2018/apr/13/surgeon-general-speaks-on-state-opioid--1/">call for alternative treatments</a>, including physical therapists. </p>
<p>The Centers for Disease Control and Prevention also issued <a href="https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm">prescribing guidelines</a> in 2016 that recommend physical therapists be considered a first-line treatment for people with chronic pain conditions. </p>
<p>Research supports these positions, including research papers studying opioid use for common musculoskeletal pain conditions like <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393575/">back</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/29073739">knee</a> and <a href="http://mcpiqojournal.org/article/S2542-4548(17)30057-7/fulltext">neck pain</a>. </p>
<p>These studies show quite convincingly that the probability of receiving a prescription for opioids is <a href="https://www.ncbi.nlm.nih.gov/pubmed/29790166">89 percent lower</a> for people seeing a physical therapist for pain. Seeing the physical therapist sooner, rather than later, makes this protective effect even <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393575/">greater</a>. </p>
<h2>Why don’t more people see a physical therapist?</h2>
<p>People in pain can go <a href="http://www.apta.org/StateIssues/DirectAccess/">directly to a physical therapist</a> in every state. So why don’t more people to do this? The simple answer: time and money.</p>
<p>Steven George, the director of musculoskeletal research for the Duke Clinical Research Institute, recently wrote, “Our existing health care system is designed to treat pain through <a href="http://thehill.com/business-a-lobbying/358037-our-inability-to-adequately-treat-pain-has-caused-tremendous-societal">easily delivered products, like opioids, injections and surgery,</a>” suggesting that alternatives are not as easily delivered.</p>
<p>Only about <a href="https://www.ncbi.nlm.nih.gov/pubmed/28441685">10 percent</a> of people who see a physician for back pain get referred to a physical therapist. Only <a href="https://www.ncbi.nlm.nih.gov/pubmed/29180553">37 percent</a> of those people actually go. The process to make an appointment can be lengthy and time-consuming, and insurance companies often slow down the process. Some <a href="https://www.bcbsm.com/index/health-insurance-help/faqs/plan-types/hmo/how-do-referrals-work-in-my-hmo-plan.html">HMO insurance plans</a> require that physical therapy treatment be certified as medically necessary, or they will not pay. And, there’s another step: pre-authorization. This, too, delays the access to covered care even more. For a person in pain and in need of help, this is a deterrent. It’s much easier to ask for a pill. </p>
<p>Then there is the cost. Physical therapists are often classified as specialists, so co-payments may be as high as <a href="https://www.aetna.com/sbcsearch/getmysbc?T=1410822&D=01-01-2017">US$75 a visit</a>. The average patient with back pain sees a physical therapist for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4393575/">seven visits</a>. Even with insurance coverage, this episode of care still will cost the person over US$500 out of pocket compared to the cost of a single primary care visit and prescription. Several states, including <a href="http://www.apta.org/Media/Releases/Legislative/2011/3/17/">Kentucky</a>, have enacted laws limiting co-payment for many services. One of the recommendations from the President’s Commission was that alternatives to opioids, including physical therapy, should be adequately covered by payers. These recommendations have yet to be acted upon.</p>
<p>So what does all of this mean for people in pain? First, seeing a physical therapist is effective for many pain conditions. Second, getting to a physical therapist sooner rather than later decreases the use of opioid medication. The current health care system must change in order for people in pain to access this safe and effective non-opioid alternative for pain management.</p><img src="https://counter.theconversation.com/content/92169/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Bishop works for University of Florida Department of Physical Therapy.
Mark receives funding from the National Institutes of Health to study conservative interventions for pain.
He serves on the Board of Directors of the Florida Physical Therapy Association. </span></em></p>As the nation grapples with its opioid addiction epidemic, one solution for many with chronic joint pain and back pain could be physical therapy. But it’s often underutilized. Here’s why.Mark Bishop, Associate Professor of Physical Therapy, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/974912018-06-21T10:26:37Z2018-06-21T10:26:37ZWhat the US can learn from other countries in dealing with pain and the opioid crisis<figure><img src="https://images.theconversation.com/files/223377/original/file-20180615-85845-1qdqt74.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The U.S. has the highest daily opioid use rate in the world.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/white-prescription-pills-spilled-onto-table-747676462?src=IehrLEh-_rLRltn66Ep3sw-1-1">Kimberly Boyles/shutterstock</a></span></figcaption></figure><p>With all the recent news on opioid overuse in the U.S., it’s not surprising that Americans consume <a href="https://www.cnbc.com/2016/04/27/americans-consume-almost-all-of-the-global-opioid-supply.html">the vast majority of the global opioid supply</a>. Daily opioid use in the U.S. is the <a href="https://qz.com/1198965/the-surprising-geography-of-opioid-use-around-the-world/">highest in the world</a>, with an estimated one daily dose prescribed for every 20 people. That rate is 50 percent higher than in Germany and 40 times higher than in Japan.</p>
<p><a href="https://www.washingtonpost.com/news/to-your-health/wp/2016/03/29/amid-heartbreaking-stories-obama-pushes-for-more-funding-to-treat-addiction/">As former U.S. Surgeon General Vivek Murthy once said</a>, the U.S. “arrived here on a path that was paved with good intentions,” but “the results have been devastating.” “We have nearly 250 million prescriptions for opioids written every year. That’s enough for every person in America to have a bottle of pills and then some,” he added. </p>
<p>Has the U.S.’s heavy reliance on prescription opioids caused more harm than good? And, likewise, have other countries’ low use of opioids caused more pain than good?</p>
<p>I have been pondering these issues at Texas A&M Health Science Center, where I am the chair of a newly established <a href="https://www.tamhsc.edu/community/opioidtaskforce/index.html">Opioid Task Force</a>, an initiative that emphasizes a multifaceted approach to the opioid epidemic. To me, it seems like most countries need to find a happy balance between the American attitude that all pain needs to be cured – and the ethos in other countries that pain is to be endured.</p>
<p><iframe id="9S1Qq" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/9S1Qq/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<h2>Differing views on pain</h2>
<p>In investigating this issue, I came across two reasons that might explain the worldwide differences in pain management strategies. </p>
<p>First, while pain is universal, pain is fundamentally <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959190/">a subjective phenomenon</a>. People from different countries <a href="https://theconversation.com/how-different-cultures-experience-and-talk-about-pain-49046">experience pain differently</a>, based on traditional beliefs rooted in social and cultural values.</p>
<p>For example, people in Africa, especially men, may be <a href="https://doi.org/10.1080/20786190.2014.977034">reluctant to admit to pain</a>, as doing so would be a sign of weakness. In contrast, Americans <a href="https://www.theatlantic.com/health/archive/2017/12/america-experiences-more-pain-than-other-countries/548822/">report more pain</a> than people from any other country, with about a third of adults reporting pain “often” or “very often.” </p>
<p><iframe id="SgC47" class="tc-infographic-datawrapper" src="https://datawrapper.dwcdn.net/SgC47/1/" height="400px" width="100%" style="border: none" frameborder="0"></iframe></p>
<p>In traditional African society, pain is viewed as something to be endured and pain medication has often been <a href="https://doi.org/10.2217/pmt.13.68">a luxury for those who could afford it</a>. Self-medication with simple analgesics and traditional herbs are often the first -— but not necessarily effective – strategies to reduce pain. </p>
<p>Secondly, many countries have <a href="https://www.vox.com/policy-and-politics/2017/8/8/16049952/opioid-prescription-us-europe-japan">much stricter regulations</a> than the U.S. regarding when opioids may and should be prescribed. </p>
<p>For example, until the past few years, there were few U.S. regulations for the medical prescription of opioids. With the goal of eliminating pain, physicians generously prescribed opioids after most surgical procedures or for routine patient complaints of pain. (It’s worthwhile to note that, thanks to new restrictions, <a href="https://www.aafp.org/news/health-of-the-public/20180425opioidstudy.html">opioid prescriptions in the U.S.</a> decreased by more than 20 percent between 2013 and 2017.)</p>
<p>Conversely, in Europe, opioids are dispensed by specialists and more tightly regulated, including restrictions on advertisements. It’s less common to dispense opioids for non-cancer related pain such as chronic back or musculoskeletal pain. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223379/original/file-20180615-85834-14h1r8x.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Alternative and complementary treatments like acupuncture could help people manage pain.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-woman-receiving-acupuncture-treatment-beauty-329803421?src=fokPgUQHWUmZqU9ST9n_Eg-1-21">Leonardo da/shutterstock</a></span>
</figcaption>
</figure>
<p>Many countries have traditionally treated pain with other approaches. With a view of pain as a condition, <a href="https://nccih.nih.gov/health/whatiscam/chinesemed.htm">Chinese medicine</a> has long incorporated the use of herbs, acupuncture and lifestyle changes to manage pain. Acupuncture has been adopted in many clinical settings around the world, including in the U.S., and is considered effective for certain pain conditions and safe when performed by an experienced practitioner. </p>
<p>With a similar aversion to narcotics and concerns about addiction, Japanese health care providers have traditionally avoided opioid prescriptions, recommending non-pharmacological treatments for dealing with pain such as acupressure, massage and relaxation techniques. Yet, with the aging of the population, there has been <a href="https://www.bloomberg.com/news/articles/2017-09-21/painkiller-sales-take-off-as-japan-s-baby-boomers-demand-relief">a greater demand for opioids</a> and growing concerns about abuse. </p>
<p>In Europe, there are positive attitudes among both the medical profession and the public alike about <a href="https://nccih.nih.gov/health/integrative-health#cvsa">complementary and alternative medicine</a> – or the use of natural products or mind and body practices developed outside of mainstream Western medicine. These approaches are increasingly <a href="https://www.pae-eu.eu/wp-content/uploads/2013/12/Survey-of-chronic-pain-in-Europe.pdf">integrated into primary care</a>, with reimbursement through national health care systems. For example, <a href="https://doi.org/10.1089/acm.2008.0306">German physicians</a> often prescribe physical therapy, exercise, massage and relaxation therapies, all of which have been associated with pain relief. However, there’s some concern about the use of unregulated natural health practitioners, as well as the need for better communication among certified medical providers, natural health practitioners and patients.</p>
<h2>A happy balance</h2>
<p>What’s the best strategy for dealing with pain? There are no simple answers. </p>
<p>What does seem clear is that pain management strategies are slowly converging in the face of the opioid crisis. Countries that have been overprescribing are now <a href="https://www.aafp.org/news/health-of-the-public/20180425opioidstudy.html">putting the brakes on uncontrolled prescriptions</a> through increased regulation and continuing education. Meanwhile, in counties with limited access to pharmacological treatments, there’s <a href="https://www.thelancet.com/commissions/palliative-care">increased recognition</a> of the rampant suffering and the need for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052588/">increased access to opiates</a> as part of an overall approach that includes traditional non-pharmacological strategies too.</p>
<p>I’m heartened to see physicians start to emphasize alternatives to opioid prescriptions as a first step in pain management, in line with <a href="https://www.cdc.gov/drugoverdose/prescribing/guideline.html">Centers for Disease Control and Prevention guidelines</a>, and practices in other countries. To go even further will require better education of both health care professionals and patients regarding complementary and alternative treatments, as well greater access to and payment for them. </p>
<p>For me, the issue goes beyond the simplistic characterizations of pain management often seen in different countries and cultures. Pain isn’t just to be cured – or to be endured. Rather, all Americans, whether providing or receiving care, need to understand what can be learned from best practices in pain management around the world.</p><img src="https://counter.theconversation.com/content/97491/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Marcia G. Ory does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Most countries need to find a happy balance between the American attitude that all pain needs to be cured – and the ethos in other countries that pain is to be endured.Marcia G. Ory, Regents and Distinguished Professor, Associate Vice President for Strategic Partnerships and Initiatives, Texas A&M UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/975932018-06-21T10:23:51Z2018-06-21T10:23:51ZOpioids don’t have to be addictive – the new versions will treat pain without triggering pleasure<figure><img src="https://images.theconversation.com/files/223042/original/file-20180613-32313-rus66u.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">shutterstock</span> </figcaption></figure><p>The problem with opioids is that they kill pain – and people. In the past three years, <a href="https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis">more than 125,000 persons</a> died from an opioid overdose – an average of 115 people per day – exceeding the number killed in <a href="https://www.cdc.gov/nchs/products/databriefs/db294.htm">car accidents and from gunshots during the same period</a>. </p>
<p>America desperately needs safer analgesics. To create them, biochemists like myself are focusing not just on the opioids, but on opioid receptors. The opioids “dock” with these receptors in the brain and peripheral nervous system dulling pain but also causing deadly side effects. </p>
<p>My colleagues and I in <a href="http://pdspdb.unc.edu/rothlab/">Bryan Roth’s lab</a> have recently <a href="http://doi.org/10.1016/j.cell.2017.12.011">solved the atomic structure</a> of a morphine-like drug interacting with an opioid receptor, and now we are using this atomic snapshot to design new drugs that block pain but without the euphoria that leads to addiction. </p>
<h2>What has caused the opioid epidemic?</h2>
<p>In the U.S., more than <a href="http://doi.org/10.1056/NEJMra1507771">one-third of the population</a> experiences some form of acute or chronic pain; in older adults this number rises to <a href="http://doi.org/10.1056/NEJMra1507771">40 percent</a>. The most common condition linked to chronic pain is chronic depression, which is a major cause of suicide. </p>
<p>To relieve severe pain, people go to their physician for powerful prescription painkillers, opioid drugs such as morphine, oxycodone and hydrocodone. Almost all the currently marketed opioid drugs exert their analgesic effects through a protein called the “mu opioid receptor” (MOR). </p>
<p>MORs are embedded in the surface membrane of brain cells, or neurons, and block pain signals when activated by a drug. However, many of the current opioids stimulate portions of the brain that lead to additional sensations of “rewarding” pleasure, or disrupt certain physiological activities. The former may lead to addiction, or the latter, death. </p>
<p>Which part of the brain is activated plays a vital role in controlling pain. For example, MORs are also present in the brain stem, a region that controls breathing. Activating these mu receptors, not only dulls pain but also slows breathing. Large doses stop breathing, causing death. Activating MORs in other parts of the brain, including the ventral tegmental area and the nucleus accumbens, block pain and trigger pleasure or reward, which makes them addictive. But so far there is no efficient way to turn these receptors “on” and “off” in specific areas.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=578&fit=crop&dpr=1 600w, https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=578&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=578&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=726&fit=crop&dpr=1 754w, https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=726&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/224266/original/file-20180621-137717-oo5qs1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=726&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Locations of the mu opioid receptor (MOR) in the brain. The red areas are locations where MOR is present and active. Labeled locations are only approximate.</span>
<span class="attribution"><span class="source">Tao Che</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>But there is another approach because not all opioids are created equal. Some, such as morphine, bind to the receptor and activate two signaling pathways: one mediating pain cessation and the other producing side effects like respiratory depression. Other drugs favor one pathway more than the other, like only blocking pain – this is the one we want. </p>
<h2>“Biased opioids” to kill pain</h2>
<p>But MOR isn’t the only opioid receptor. There are two other closely related proteins called kappa and delta, or KOR and DOR respectively, that also alter pain perception but in slightly different ways. Yet, currently there are only a few opioid medications that target KOR, and none that target DOR. One reason is that the function of these receptors in the brain neurons remains unclear. </p>
<p>Recently KOR has been getting attention as <a href="http://doi.org/10.1126/scisignal.aai8441">extensive</a> <a href="http://doi.org/10.1124/jpet.114.216820">studies</a> from different academic labs show that it blocks pain without triggering euphoria, which means it isn’t addictive. Another benefit is that it doesn’t slow respiration, which means that it isn’t lethal. But although it isn’t as dangerous as MOR, activating KOR does promote <a href="https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024720/">dysphoria</a>, or unease, and sleepiness.</p>
<p>This work suggests it is possible to design a drug that only targets the pain pathway, without side effects. These kind of drugs are called “biased” opioids. </p>
<h2>Discovering and designing drugs to target KOR</h2>
<p>So far, there are two popular ways to discover new drugs. The first involves using existing commercially available libraries of compounds and testing them on cells or animals to find one that has the required characteristics. This hit-and-miss approach is straightforward but time-consuming, running anywhere from three months to two years to screen between 3,000 to 20,000 compounds. </p>
<p>The other strategy is called “structure-based drug design.” With this approach, you first need a high-resolution photograph of the receptor – showing the arrangement of every atom in the molecule. Then, using a computer program, you can examine up to 35 million molecules from a virtual chemical library called <a href="http://zinc15.docking.org">ZINC 15</a> to find a molecule that will precisely interact – lock-and-key style – with the receptor. It is like having the precise dimensions of the International Space Station so that you can design a spacecraft that can fits perfectly in the docking site. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=196&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=196&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=196&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=246&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=246&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223913/original/file-20180619-126556-1om1xyw.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=246&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The receptor and drug are like a lock and key. The drug needs to fit the receptor perfectly to trigger a signal.</span>
<span class="attribution"><span class="source">Tao Che</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>I’m a crystallographer, which means I specialize in taking atomic resolution photographs of proteins. I became interested in solving the structure of KOR – when the protein is in its active state bound to a drug.</p>
<p>Structure is considered the gold standard for figuring out how a drug interacts with a receptor and produces a signal. To solve the KOR structure, I first manufactured the KOR protein to make KOR crystals, which consists of hundreds of millions of KOR molecules stacked in the same way, just like salt molecules in a salt crystal. Then I blasted the crystals with X-rays to generate an image of the receptor at atomic level. The key to these pictures was that I “froze” the KOR proteins in their active state to understand how these receptors interact with a drug. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=189&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=189&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=189&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=238&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=238&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223902/original/file-20180619-126531-14j1mh5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=238&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">X-ray crystallography. These action shots of KOR show how the receptor (blue) and drug (pink) fit together to trigger a signal that blocks pain.</span>
<span class="attribution"><span class="source">Tao Che</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>With an action shot of KOR, we recognized what parts of the molecule are critical for blocking pain signals. We are now using this structural data to construct a “biased” molecule that only activates the pain-blocking parts of the protein without triggering side effects. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=226&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=226&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=226&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=284&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=284&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223914/original/file-20180619-126543-1292ilj.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=284&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Now that we have an ultra high-resolution picture of the KOR receptor interacting with an opioid, we can now design a new, safer version that fits snugly in the receptor and only blocks pain.</span>
<span class="attribution"><span class="source">Tao Che</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Deciphering the structure of a protein is also valuable for creating a drug that interacts only with only one receptor. All the members of the opioid receptor family – MOR, KOR and DOR – look similar, like siblings. Therefore, these high-resolution photos are essential for designing drugs that will only recognize and target KOR. </p>
<p>Our structure is now used for virtual drug screening where the computational program randomly inserts millions of compounds into the structure and ranks each of them based on how well they fit. The better the score, the more likely that compound will yield a drug. </p>
<p>The exciting news is that researchers in the Roth lab have discovered several promising compounds based on the KOR structure that selectively binds and activates KOR, without cavorting with the more than 330 other related protein receptors. </p>
<p>Now our challenge is to transform these molecules into safer drugs.</p><img src="https://counter.theconversation.com/content/97593/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Tao Che receives funding from the National Institute of Drug Abuse. (Grant number: DA035764) </span></em></p>Scientists have taken atomic resolution snapshots of an opioid receptor interacting with a drug. Now they are using these images to design “biased” opioids that block pain without the dangerous side effects.Tao Che, Postdoctoral Research Associate at Department of Pharmacology, University of North Carolina at Chapel HillLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/980622018-06-20T10:27:44Z2018-06-20T10:27:44ZA way around opioids: Target the type of pain for better pain relief<figure><img src="https://images.theconversation.com/files/223917/original/file-20180619-126540-ks9zl.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">As doctors have learned more about the types of pain, they can better tailor treatment.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/toothache-suffering-young-man-teeth-problems-73929085?src=6hZeXqHqjc18l27wJCCGgQ-3-44">Dundanim/Shutterstock.com</a></span></figcaption></figure><p>In the old days, pain was pain, and there was not a lot of differentiating on the best way to treat it. Then came along <a href="https://www.history.com/topics/history-of-heroin-morphine-and-opiates">powerful morphine in the late 1800s</a>, and more than a century later, <a href="https://www.drugabuse.gov/publications/research-reports/misuse-prescription-drugs/what-scope-prescription-drug-misuse">powerful opioid painkillers</a>. Marketing by opioid manufacturers led many people to believe, <a href="http://fortune.com/2018/05/16/oxycontin-purdue-pharma-lawsuit-tennessee-florida-opioid-epidemic/">several lawsuits claim</a>, that there were few downsides to using powerful opioids to treat pain. Well, we know differently now.</p>
<p>At the same time we saw the <a href="https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates">rise of deaths due to opioids</a> in the past decade, research revealed the nuances of pain. A modern medical approach, emphasized even more in the wake of new <a href="https://www.cdc.gov/drugoverdose/prescribing/guideline.html">Centers for Disease Control and Prevention recommendations</a> on prescribing opioids for pain, is to consider non-opioid painkillers first. </p>
<p>As a physician and pain researcher, I can say this is not as easy as it sounds, because there are different kinds of pain and because people experience pain differently. As a pain specialist, I’ve learned to use a broad array of treatments, including dozens of non-opioid pain medications, to treat the type of pain my patients describe and what I diagnose. Now, we need every clinician to practice this way, and to do so, we need to start at the beginning. An essential part of treating pain is to first identify what type of pain a person is having and then use a targeted treatment. </p>
<h2>Three broad categories of pain</h2>
<p>Broadly speaking, the medical community now knows there are three types of pain: <a href="https://www.healthline.com/health/nociceptive-pain">nociceptive</a> pain, <a href="https://www.theacpa.org/conditions-treatments/conditions-a-z/neuropathic-pain/">neuropathic</a> pain and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290396/">inflammatory pain</a>.</p>
<p>Nociceptive pain is experienced when pain receptors, called nociceptors, are activated. For example, go ahead and pinch your skin right now. The pain happens because pressure receptors are being activated on nerves, and pain signals travel quickly to your brain. Some pain nerves have these special receptors, and others have bare nerve endings that can be activated by pressure, stretch, extreme temperature, chemicals or movement. The activated nerve endings send pain signals to the spinal cord and up to the brain. Nociceptive pain is a normal response to insult or injury because it tells the person to protect themselves from further injury. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223918/original/file-20180619-126550-i6n0wk.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The pain from a broken arm is an example of nociceptive pain.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/male-doctor-bandaging-hand-little-patient-517906939?src=L0fl3HRSYCxH9hWQZiheGw-1-4">PRESSLAB/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Nociceptive pain can be divided into two types – <a href="https://www.ncbi.nlm.nih.gov/books/NBK12991/">somatic</a>, with receptors that monitor the musculoskeletal system, or <a href="https://www.ncbi.nlm.nih.gov/books/NBK12991/">visceral</a>, with receptors that exist in the lining of intestines. Somatic nociceptive pain results from a broken arm, for example. If a person holds really still and doesn’t move the arm, the pain is not intense. But if a person moves, all the somatic nerve receptors in the bone and muscle are activated and pain is severe. </p>
<p>A stomach ulcer is an example of visceral pain. If the stomach and intestines are quiet, there may be little or no pain, but as soon as the stomach and intestines start moving, the pain receptors around the ulcer are activated and severe sharp, burning pain is felt. </p>
<p>Neuropathic pain is felt when nerve fibers are damaged or malfunctioning. A classic example is <a href="https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/nerve-damage-diabetic-neuropathies">diabetic peripheral neuropathy</a>, where patients with diabetes feel like pins and needles are stabbing them in their fingers and toes. That is because nerves have been damaged by high levels of sugar. Think of it like a fallen electric power line that has lost its insulation and is now sparking and zapping randomly on the ground. Those random zaps are injured nerves spontaneously firing and sending false signals to the brain that there is something causing pain. Neuropathic pain is <a href="https://link.springer.com/chapter/10.1007/978-3-319-64922-1_4">pathologic pain</a>, which means that it is considered abnormal. It is not a protective response, as is nociceptive pain; it is a malfunction. </p>
<p>Inflammatory pain is caused by inflammation, the body’s response to injury or infection. In inflammatory diseases, such as infection, traumatic injury, burns, cuts, arthritis, inflammatory bowel disease or autoimmune diseases, the region around the nerve is inflamed. There, an inflammatory soup of pain signal molecules, such as <a href="http://www.pnas.org/content/105/9/3351">TGN-alpha</a>, IL-1, IL-6 and ATP, lower the threshold for nerve firing, so even the slightest thing sets them off. Inflammation causes nerves to signal pain much easier than they otherwise would. </p>
<p>It makes sense to use pain medicines if the pain is severe, in all three types. If it isn’t really that bad, then non-medicine treatments are better. Elevate your leg, stretch your muscles, put ice on that charley horse. All that works well. Often, <a href="https://www.ncbi.nlm.nih.gov/pubmed/29705466">movement</a>, <a href="https://www.ncbi.nlm.nih.gov/pubmed/27206497">coping strategies</a>, and time for the body to heal are truly the best remedy. </p>
<p>If medication is needed, there are medications geared for each type.</p>
<h2>Different pain, different treatment</h2>
<p>Let’s look again at the example of the broken arm. If you don’t move it, it doesn’t hurt as much because the pain receptors are not being activated. So protect the arm, stabilize it, and get it fixed. Treat nociceptive pain by looking for the cause and treating the cause. If you stop the cause, the acute pain will resolve. So, immobilize the arm, realign the bone in surgery, and put a cast on it until it heals. In many instances, no pain medicine is needed. But it’s okay to use medicine for moderate and severe pain. Medications in this case can help you tolerate the fix and speed up rehabilitation and recovery. </p>
<p>Severe nociceptive pain can be controlled by starting with non-opioids and adding other medications as needed. Don’t stop the non-opioid pain medicines. You may think they weren’t working because the pain was too severe, but when used in combination with opioids, medicines like Tylenol and ibuprofen are what we doctors call opioid-sparing. This means that if a person needs more than Tylenol or ibuprofen, a smaller amount of opioid will be needed to control the pain if opioids are combined with non-opioids. This significantly lowers the risk of using opioids. </p>
<p>Nerve pain caused by damaged nerves is targeted by nerve pain medicines. <a href="https://www.medicinenet.com/gabapentin/article.htm">Gabapentin</a> is probably the most common, but again, there are several options. Finding the one that works best with the fewest side effects for an individual person is the key.</p>
<p>Inflammatory pain best responds to drugs called anti-inflammatories. There are non-steroidal anti-inflammatory drugs (NSAIDs), and steroids used to treat inflammation and reduce inflammatory pain. Aspirin, ibuprofen and naproxen are NSAIDs. Steroids, such as cortisone, have side effects of their own.</p>
<p>Many of these drugs were not originally developed to treat pain, so they are used by doctors “<a href="https://www.fda.gov/ForPatients/Other/OffLabel/default.htm">off-label</a>” because doctors and other clinicians noticed that they were beneficial for targeted pain treatment. </p>
<p>For example, gabapentin’s traditional use is to <a href="https://www.medicinenet.com/gabapentin/article.htm">stop seizures</a>. If I prescribe it for pain, I explain it like this: Gabapentin can be used at really high doses, and is strong enough to prevent a seizure. I compare that dose to a very high volume, like listening to music so loud it might give you a headache. On the other hand, a low dose of gabapentin, like playing a stereo quietly in the background so the music is barely noticeable, calms overexcited nerves. This is how I and others use it to treat diabetic neuropathy, <a href="https://www.mayoclinic.org/diseases-conditions/sciatica/symptoms-causes/syc-20377435">sciatica</a> and even nerves injured from normal surgery.</p>
<p>All of this may seem complicated, and brings up many good questions that providers and patients have. Let me respond to the questions with a series of answers. </p>
<p><strong>Can all three pain types occur together?</strong></p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223919/original/file-20180619-126556-1aw9ohu.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A patient after surgery may feel three kinds of pain at once.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/close-surgery-team-operating-573583255?src=EqGrIb2RnoHAJezfJUEw7w-1-2">gpointstudio/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Yes, people can have only one pain type or all three pain types at the same time. After surgery, a patient will have nociceptive, neuropathic and inflammatory pain. So in this case, using a combination of medications is more effective and safer than trying to treat all the pain types with one drug.</p>
<p>This means that a person with all three types of pain may take multiple medicines to most effectively treat it all. Low doses of combinations of medications are often more effective and safer. This is why when drugs become generic, they often are combined into combo pills for the best effect. This is known as synergism. But, this also means that if a person only has one type of pain, a single targeted prescription may be all they need.</p>
<p><strong>Are opioids still good medicines to use?</strong></p>
<p>Yes, targeted pain treatment with non-opioid pain medicines may not be enough, and some patients will still need opioids. The severity of pain may be overwhelming, and opioids indiscriminately block pain sensation. Opioids are still an indispensable tool in the doctor’s toolkit for many diseases. </p>
<p><strong>Are newer pain medicines being developed?</strong></p>
<p>Yes, because of the opioid crisis, alternative options that are safer and have fewer side effects are appropriately being sought out. Many old drugs are being revived, reformulated and re-evaluated with new research methods. While researchers discover new benefits of <a href="https://www.ncbi.nlm.nih.gov/pubmed/29390443">ketamine</a> and its cousin <a href="https://www.ncbi.nlm.nih.gov/pubmed/28877137">memantine</a> for treatment of depression and memory loss respectively, each is finding resurgent use for treatment of pain. </p>
<p><strong>Does marijuana treat pain?</strong></p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=504&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=504&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223920/original/file-20180619-126540-31j39a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=504&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Marijuana can treat pain, but researchers need to understand the mechanisms better.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/medical-marijuana-close-cannabis-buds-doctors-488508634?src=isBFTLuqR_umjtVyJA_Llw-1-12">BestStockFoto/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Yes, marijuana can treat pain. The active ingredients in marijuana are similar to fat molecules our own body makes, called <a href="https://emedicine.medscape.com/article/1361971-overview">endocannabinoids</a>. Endocannabinoids are retrograde messengers, meaning they travel backwards from one nerve to the nerve upstream to turn it off. But, turning off nerves indiscriminately can have some pretty horrible side effects, so researchers are trying to identify exactly which cannabinoids work best in specific body areas and for specific disease types. Once we have better research data, using marijuana-like molecules may become a targeted pain treatment. </p>
<p>Today, in this decade, targeted pain treatment is modern medical practice. I believe future decades will look different, as newer medicines are developed and non-medicine options are emphasized. Already, even major surgeries are being done using targeted pain treatment with <a href="https://www.ncbi.nlm.nih.gov/pubmed/29661153">improved pain control</a> and with <a href="https://www.ncbi.nlm.nih.gov/pubmed/29555468">safer outcomes</a>. Non-medicine pain control options coupled with targeted pain medicine treatments when needed, is what the doctor should be ordering today.</p><img src="https://counter.theconversation.com/content/98062/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>David A. Edwards is involved in many research trials to bring new treatments to patients. For 2 studies, he receives research grant funding from Grunenthal and Semnur, Inc. Dr. Edwards does not accept any compensation from companies or political bodies. Dr. Edwards is a board member of the Tennessee Pain Society.</span></em></p>As knowledge of pain and the highly addictive nature of opioids has grown, so has the knowledge grown about pain and its origins. A pain specialist explains the intricacies, and how treatment is changing as a result.David A. Edwards, Division Chief, Pain Medicine, Vanderbilt UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/974302018-06-19T10:23:33Z2018-06-19T10:23:33ZOpiate addiction and the history of pain and race in the US<figure><img src="https://images.theconversation.com/files/223062/original/file-20180613-32339-9r3jhf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pain of the sick: 'Anatomy of Expression,' by Sir Charles Bell, 1806.</span> <span class="attribution"><a class="source" href="https://wellcomecollection.org/works/avakmubu?query=pain">Wellcome Collection</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>“I have had little or no sleep, owing to the tooth ache or rather stump ache,” Elizabeth Drinker wrote in <a href="https://books.google.com/books?id=Zw67boMtNYUC&pg=PA161&lpg=PA161&dq=diary+of+elizabeth+drinker+%22stump+ach%22&source=bl&ots=r8LreFwceH&sig=VjvfVPt4hjQfVn1yxdsvP8SFwlI&hl=en&sa=X&ved=0ahUKEwiyhYqkvMLbAhVOzVMKHZlZCSQQ6AEIKTAA#v=onepage&q&f=false">her diary</a> one night in 1796. “One of my Eye teeth very sore, my face much swelled and painful.” </p>
<p>Drinker, a white woman from a prominent family in Philadelphia, filled her diary with comments like this. Disease was rampant in those days, and injuries often didn’t heal properly. Food was frequently spoiled, leading to painful stomach problems. Cavities and severe gum disease were common. These and other problems meant that pain – severe, intractable pain – was an ordinary part of daily life. </p>
<p>Of course, many people suffered far more than Elizabeth Drinker. Slaves, in particular, were forced to perform long hours of grueling work, and their injuries and illnesses were often left untreated. They also suffered from brutal physical punishment. In his 1845 <a href="https://www.gutenberg.org/files/23/23-h/23-h.htm">autobiography</a>, Frederick Douglass described how the overseer on his plantation whipped his aunt: “No words, no tears, no prayers, from his gory victim, seemed to move his iron heart from its bloody purpose. The louder she screamed, the harder he whipped; and where the blood ran fastest, there he whipped longest.”</p>
<p>It is worth considering this history in the current opiate crisis. I am a researcher who has closely studied drug use in the U.S. in the 19th century. I see many parallels between the past and today in the shameful way people of different races are treated when it comes to pain and to drug addiction. </p>
<h2>Rise of narcotics</h2>
<p>When Drinker was alive, people did not have many options for treating pain. The only really effective treatment was opium, taken as a tincture in an alcohol solution. Opium could dull minor and perhaps moderate pain, but if you crushed your foot in an accident, nothing could be done for your agony. </p>
<p>Plus, since opium also caused constipation, nausea and vomiting – all of which could be serious medical problems in their own right – people only used it in modest amounts. </p>
<p>Slaves were rarely given opium for their pain. Their illnesses and injuries were often left untreated. But it was also <a href="http://www.jstor.org/stable/3561773">widely assumed</a> that different types of people felt pain more or less strongly. The poor supposedly felt less pain than the rich, while men felt less pain than women and blacks felt less than whites. Physicians and slave owners therefore believed that when slaves claimed to be hurt, they were probably lying. They also believed that whippings had to be severe to be effective.</p>
<p>Opium was not particularly helpful for severe pain, but injected morphine was. Morphine was first isolated from opium around 1805, but it was rarely used for the next five decades, because it was difficult to tolerate when taken by mouth. In 1856, Scottish physician Alexander Wood invented the hypodermic needle. He discovered that injected morphine gives fast and highly effective relief for even excruciating pain. </p>
<p>Injected morphine was first widely used during the Civil War. After the war, it was <a href="https://archive.org/stream/injuriesofnerves00mitcuoft#page/n3/mode/2up/search/morphia">used to help wounded veterans</a> cope with their injuries, and then became a popular way to <a href="https://books.google.com/books?id=MV4ApfmtEx0C&printsec=frontcover&dq=morphia&hl=en&sa=X&ved=0ahUKEwj618nN6MTbAhVHh1QKHWp2CEwQ6AEIKTAA#v=onepage&q&f=false">treat acute pain of all kinds</a>. </p>
<h2>Responses to addiction</h2>
<p>For many people, morphine was a godsend. However, serious problems accompanied its widespread use. People began to inject morphine for recreational purposes and to escape despair. <a href="https://bklyn.newspapers.com/image/50430595/">Suicide</a> and overdoses became common. Others became addicted to morphine as well as other intoxicating drugs at the time, including cocaine and hashish.</p>
<p>By the end of the century, physicians were debating whether or not addiction should be considered a disease. Reformers passed the <a href="https://www.academia.edu/1876102/Restricting_the_Sale_of_Deadly_Poisons_Pharmacists_Drug_Regulation_and_Narratives_of_Suffering_in_the_Gilded_Age">first wave of laws</a> intended to control narcotics and other drugs. They also <a href="https://chestnut.org/Lighthouse-Institute/Bookstore/Product-Details/slaying-the-dragon-the-history-of-addiction-treatment-and-recovery-in-america-second-edition">established treatment facilities</a> to help people recover from their addiction. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=908&fit=crop&dpr=1 600w, https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=908&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=908&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1141&fit=crop&dpr=1 754w, https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1141&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/223066/original/file-20180613-32339-tzb2oi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1141&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Clear glass shop round for liquid morphine.</span>
<span class="attribution"><a class="source" href="https://wellcomecollection.org/works/ayd5f97k">Science Museum, London</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>According to <a href="http://www.umass.edu/umpress/title/secret-leprosy-modern-days">historian Timothy Hickman</a>, these efforts divided drug users into two types. People who became addicted after using morphine or other drugs to treat their pain were often <a href="https://chroniclingamerica.loc.gov/lccn/sn89081128/1899-04-05/ed-1/seq-8/">described as sympathetic victims</a> and <a href="https://jamanetwork.com/journals/jama/article-abstract/852925">given help</a>. People who used drugs for recreational reasons, however, were considered <a href="https://chroniclingamerica.loc.gov/lccn/sn85058130/1906-07-01/ed-1/seq-3/">“degraded”</a> and put in prison. </p>
<p>In practice, of course, the difference between the two categories was often blurry. People who became addicted trying to control their pain were frequently incarcerated under the faulty assumption that their continued use was a personal choice. They were also mistaken for people who took drugs solely for recreational reasons. </p>
<p>There was also an important racial component to all this. After the Civil War, the widespread suffering of freed slaves was <a href="https://www.nytimes.com/2012/06/11/books/sick-from-freedom-by-jim-downs-about-freed-slaves.html">ignored by policymakers and the media</a> as part of the effort to reunite the nation. It was also ignored by white physicians. Although statistics from the period are unreliable, it appears that blacks were prescribed morphine significantly less often than whites – in part because <a href="https://books.google.com/books?id=xLBzqlwN66gC&printsec=frontcover&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false">they received less medical care</a> and in part because <a href="https://books.google.com/books?id=W1A2ULen_-QC&pg=PA25&dq=negro+pain&hl=en&sa=X&ved=0ahUKEwj_iq_5usLbAhVQ7FMKHc3mDCkQ6AEIKTAA#v=onepage&q&f=false">white physicians assumed</a> that they suffered less physical pain. </p>
<p>Like whites, blacks sometimes used other drugs that authorities found concerning. Unlike whites, however, blacks were rarely offered sympathy or treatment for their addiction. White authorities almost always assumed that blacks used these substances for “degraded” reasons. Although whites were sometimes given sympathy and treatment even if they were considered degraded, blacks rarely were. Black addicts simply were not understood as sympathetic victims in the same way as many whites. They were seen only as dangerous criminals and often described in <a href="https://books.google.com/books?id=e20cAQAAMAAJ&pg=PA247&dq=negro+%22drug+habit%22&hl=en&sa=X&ved=0ahUKEwiDlKyz8cTbAhVwp1kKHZTYAlwQ6AEITjAH#v=onepage&q&f=false">racist terms</a>. </p>
<h2>Lessons for today</h2>
<p>Today, Americans live with the consequences of this history. We all benefit from the ability of physicians to relieve serious pain by prescribing narcotics. Yet these drugs also cause immense harm, just as injected morphine did more than a century ago. And many still have a deeply confused reaction to addiction, mistaking people who cannot control their drug habits with people who take drugs for other reasons. </p>
<p>The mistaken belief that blacks suffer from less physical pain than whites <a href="https://doi.org/10.1073/pnas.1516047113">still persists</a> among medical students and physicians. So does the <a href="https://doi.org/10.1371/journal.pone.0159224">assumption</a> that black people are more likely to seek narcotics for supposedly illegitimate reasons. Black people receive <a href="https://doi.org/10.1001/jama.2007.64">less</a> <a href="https://doi.org/10.1111/j.1526-4637.2011.01310.x">treatment</a> for both acute and <a href="https://doi.org/10.1111/pme.12555">chronic pain</a> than whites. </p>
<p>Prescription practices by physicians are only one cause for opiate addiction in this country. Illegal drug use also plays an important role in both white and black communities. Blacks use illegal drugs at roughly the same overall rate as whites, yet <a href="https://www.nap.edu/read/18613/chapter/4">their rate of incarceration</a> is three to four times higher. They also <a href="https://doi.org/10.1377/hlthaff.2011.0983">receive</a> less effective treatment for drug addiction than whites. </p>
<p>The lessons here are stark. As a country, the U.S. responds to drug epidemics in very different ways depending on the skin color of the communities involved. At the same time, we have historically treated the pain of whites far more seriously than we have that of blacks. In my view, the country needs more treatment, and less prison, for people who struggle with addiction. We also need effective pain relief for everyone.</p><img src="https://counter.theconversation.com/content/97430/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Joseph M. Gabriel does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>In today’s opioid crisis, why are some people with addictions treated with empathy and others with disdain? The answer to that question has roots in the 19th century.Joseph M. Gabriel, Associate Professor of History and Social Medicine, Florida State UniversityLicensed as Creative Commons – attribution, no derivatives.