tag:theconversation.com,2011:/id/topics/pain-killer-11287/articlesPain killer – The Conversation2020-10-18T19:05:42Ztag:theconversation.com,2011:article/1480872020-10-18T19:05:42Z2020-10-18T19:05:42ZHippocrates and willow bark? What you know about the history of aspirin is probably wrong<figure><img src="https://images.theconversation.com/files/363828/original/file-20201015-17-1b443qn.jpg?ixlib=rb-1.1.0&rect=47%2C3%2C1158%2C811&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Hippocrates,_Aphorismi,_manuscript._Wellcome_L0002463.jpg">Wellcome Images</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Aspirin is one of the most widely used drugs in the world. Its main ingredient comes from a natural product, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Salicin">salicin</a>, found in plants such as willow and myrtle.</p>
<p>Aspirin is also a good example of how myths build up around ancient medicines.</p>
<p>Its origins have been closely linked with <a href="https://theconversation.com/hippocrates-didnt-write-the-oath-so-why-is-he-the-father-of-medicine-32334">Hippocrates</a>, the famous ancient Greek doctor and so-called father of medicine. He’s said to have used willow for pain relief, inspiring the development of aspirin centuries later.</p>
<p>But his writings barely mention willow. So why do we still believe the myth?</p>
<h2>What’s all this about willow?</h2>
<p>Practically every history of aspirin tells you Hippocrates prescribed willow to women in labour. Some say he prescribed <a href="https://www.pharmaceutical-journal.com/news-and-analysis/infographics/a-history-of-aspirin/20066661.article?firstPass=false">willow leaf tea</a>. Others say he told them to <a href="http://pennstatehershey.adam.com/content.aspx?productId=107&pid=33&gid=000281">chew willow bark</a>. </p>
<p>But when we look at what Hippocrates actually wrote, there is just <a href="https://archive.org/details/uvrescompltes02littgoog/page/n225/mode/2up">one reference</a> to burning willow leaves to make smoke for “fumigating” the uterus to get rid of a miscarried pregnancy.</p>
<p>This is pretty much <a href="https://www.gizmodo.com.au/2020/04/which-ancient-medicines-turned-out-to-be-real/">the only reference</a> to willow — ιτεα or <em>itea</em> — as a drug in these writings.</p>
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Read more:
<a href="https://theconversation.com/hippocrates-didnt-write-the-oath-so-why-is-he-the-father-of-medicine-32334">Hippocrates didn’t write the oath, so why is he the father of medicine?</a>
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<h2>Could willow actually relieve pain?</h2>
<p>Willow bark and leaves were used in some ancient medicines. However, these were often used externally, rather than swallowed. Because ancient weights and measures are confusing — and sometimes missing altogether in recipes — it’s hard to tell whether there was enough salicin in an ancient recipe to make a difference.</p>
<p>The bark of white willow (<em>Salix alba</em>), which Hippocrates may have been talking about, doesn’t contain much salicin, compared with other willows and salicin-rich plants like the myrtle tree. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Botanical drawing of white willow" src="https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=839&fit=crop&dpr=1 600w, https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=839&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=839&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1055&fit=crop&dpr=1 754w, https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1055&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/363830/original/file-20201015-13-1w1pgzi.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1055&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">The bark of white willow doesn’t contain much salicin.</span>
<span class="attribution"><a class="source" href="https://www.rawpixel.com/image/568357/white-willow-branch">Raw Pixel/Public Domain</a></span>
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<p>A clinically effective dose of 60–120mg of salicin would be very <a href="https://www.drugs.com/npp/willow-bark.html">hard to obtain</a> from simply chewing white willow bark or drinking willow tea. </p>
<p>White willow also contains toxic, bitter-tasting <a href="https://pubmed.ncbi.nlm.nih.gov/32704312/">tannins</a>. These would make it hard to consume enough bark or tea to reach that dose, and would cause stomach pain long before you got there. </p>
<p>Natural salicin is more abundant in other ancient plants, such as the myrtle tree. But even then you would still probably give yourself a <a href="https://www.healthline.com/health/willow-bark-natures-aspirin#forms-and-dose">terrible stomach ache</a> after ingesting enough of the plant to relieve pain.</p>
<p><a href="https://www.nlm.nih.gov/hmd/greek/greek_dioscorides.html">Dioscorides</a> was an ancient Roman who wrote a <a href="http://www.cancerlynx.com/BOOKONEAROMATICS.PDF">guidebook of medicines</a>, still in print today. He described willow as a remedy for stomach ache, the respiratory disease tuberculosis, and as a contraceptive. </p>
<p>He said if you burned willow bark, soaked it in vinegar, then rubbed it on corns and calluses, it would remove them. He also recommended a hot pack containing willow leaves for <a href="https://theconversation.com/got-gout-heres-what-to-eat-and-avoid-50239">gout</a> (which we know now as a type of <a href="https://arthritisaustralia.com.au/types-of-arthritis/gout/">arthritis</a>).</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627856/">Celsus</a>, another Roman medical writer, <a href="http://www.perseus.tufts.edu/hopper/text?doc=Perseus%3Atext%3A1999.02.0142%3Abook%3D6%3Achapter%3D18">said</a> warm willow packs or poultices would treat a prolapse of the womb or bowel (where the organ literally falls out of the body). Celsus advised to push it back in, and then bandage the warm dressing on the outside. </p>
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Read more:
<a href="https://theconversation.com/avicenna-the-persian-polymath-who-shaped-modern-science-medicine-and-philosophy-142667">Avicenna: the Persian polymath who shaped modern science, medicine and philosophy</a>
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<p>Salicin is used today to treat corns and warts. But this doesn’t mean Dioscorides’ recipe worked because of the salicin. Vinegar is acidic and is said to <a href="https://www.thehealthy.com/foot-care/home-remedies-for-corns-calluses/">soften corns on its own</a>. Applying any kind of warm pack <a href="https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/ice-packs-vs-warm-compresses-for-pain">will also relieve pain</a>.</p>
<p>If willow bark and leaves were handy and potent painkillers, we would have used them almost to extinction by now. Instead, by early modern times in Europe, willow was considered <a href="https://recipes.hypotheses.org/7473">largely useless as a medicine</a>. </p>
<p>This doesn’t mean willow was actually useless. It still contained salicin, but this hadn’t yet been isolated or refined into its modern form.</p>
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Read more:
<a href="https://theconversation.com/leaders-as-healers-ancient-greek-ideas-on-the-health-of-the-body-politic-135028">Leaders as healers: Ancient Greek ideas on the health of the body politic</a>
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<h2>So, if it wasn’t Hippocrates, who was it?</h2>
<p>It was English cleric <a href="https://worldneurologyonline.com/article/controversial-story-aspirin/">Reverend Edward Stone</a> who “rediscovered” willow.</p>
<p>In around 1757, Stone chewed on white willow bark out of curiosity and was struck by how bitter it was. He wondered whether it could be used medicinally, like the bitter cinchona bark (where the malaria drug <a href="https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-10-144">quinine</a> comes from). </p>
<p>Stone gathered and dried around half a kilogram of willow bark, then ground it to powder, before taking small doses every four hours to reduce his fever. Drying the bark would have concentrated the salicin, making its effect stronger.</p>
<p>When the powder seemed to relieve his fever, Stone tried it on his parishioners when they were sick. In 1763, he <a href="https://royalsocietypublishing.org/doi/10.1098/rstl.1763.0033">wrote to the Royal Society</a>, reporting it worked.</p>
<h2>How did a plant extract turn into aspirin?</h2>
<p>Italian researchers <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093759/">Brugnatelli and Fontana</a> managed to extract salicin from willow bark in 1826. Then German pharmacologist <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894700/">Johann Andreas Buchner</a> created the name “salicin” in 1828 from the Latin word for willow, <em>salix</em>. </p>
<p>Felix Hoffmann, a researcher at the German company now known as Bayer, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894700/">chemically modified</a> the related molecule salicylic acid, which was eventually named aspirin. The company patented the name <a href="https://www.history.com/this-day-in-history/bayer-patents-aspirin">in 1899</a>.</p>
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<a href="https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="White aspirin pills in a grid on a blue background" src="https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/363343/original/file-20201014-17-czfu38.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Aspirin is one of the most widely used medicines today.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/danielfoster/29719998118/">Daniel Foster/flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-sa/4.0/">CC BY-NC-SA</a></span>
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<p>Today aspirin is used for pain relief, reducing swelling, lowering body temperature and preventing blood clots.</p>
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Read more:
<a href="https://theconversation.com/weekly-dose-aspirin-the-pain-and-fever-reliever-that-prevents-heart-attacks-strokes-and-maybe-cancer-64440">Weekly Dose: aspirin, the pain and fever reliever that prevents heart attacks, strokes and maybe cancer</a>
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<h2>Why do we keep repeating the willow myth?</h2>
<p>Researchers keep repeating the myth that ancient people understood the link between willow and salicin for pain relief, partly because everyone loves an epic tale. And the story of aspirin can be turned into one, with a bit of imagination. But it’s a good reminder to look at original texts if you can. </p>
<p>It’s also an example of how <a href="https://www.psychologytoday.com/au/blog/science-choice/201504/what-is-confirmation-bias">confirmation bias works</a>. We know salicin is in willow, and salicin relieves pain. So when we find ancient references to willow, we think ancient people discovered salicin before us.</p>
<p>Modern medicine likes a respectable family tree. It helps give today’s manufactured products a good pedigree. It also helps us think of these products as safe, beneficial and part of a long healing tradition. </p>
<p>But the “ancient” history of aspirin has a lot of holes in it. So next time you pop an aspirin, thank Hoffmann rather than Hippocrates.</p><img src="https://counter.theconversation.com/content/148087/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Philippa Martyr does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Every time you pop an aspirin, thank the German chemist Hoffmann and not Hippocrates.Philippa Martyr, Lecturer, Pharmacology, Women's Health, School of Biomedical Sciences, The University of Western AustraliaLicensed 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>
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<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">
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<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>
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<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>
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<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>
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</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/714332017-02-06T10:34:01Z2017-02-06T10:34:01ZAre over-the-counter painkillers a waste of money?<figure><img src="https://images.theconversation.com/files/154035/original/image-20170124-465-125m2sp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Horses for courses?</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/paracetamol-on-white-background-382039522?src=IPwPgPK4D9nnVUMq0XwMew-1-1">Shutterstock</a></span></figcaption></figure><p>Simple painkillers (such as aspirin, paracetamol and ibuprofen) are widely bought over the counter and prescribed by doctors. But the stark truth is that most of these medicines don’t work very well. </p>
<p>Professionals can’t be satisfied advising consumers and patients to take ineffective medicines. And consumers and patients can’t be happy that they’re spending cash or NHS resources on something that doesn’t do the job. But those with minor ailments who opt for such drugs aren’t necessarily wasting their money – and may well be saving yours by reducing the burden on health services.</p>
<p>An evidence-based approach to pain relief must consider realistic alternatives. Trials demonstrate that simple over-the-counter (OTC) painkillers, such as <a href="http://www.cochrane.org/CD012230/BACK_paracetamol-low-back-pain">paracetamol for low back pain</a> and <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011888.pub2/abstract">aspirin for episodic tension-type headaches in adults</a>, work no better than placebo. But in practice, we need to consider how harmful this really is – and what people would do if they weren’t popping their favourite pills. </p>
<p>Cochrane reviews are internationally-recognised <a href="http://uk.cochrane.org/about-us">systematic reviews</a>. The most recent <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011888.pub2/abstract">review of asprin</a> for the treatment of occasional, acute, tension-type headache tells us that patients taking active medication are unlikely to be pain free. However, over half the patients taking aspirin were satisfied with their treatment, as were one third taking placebo. </p>
<p>Similarly, in a <a href="http://www.cochrane.org/CD012230/BACK_paracetamol-low-back-pain">Cochrane review</a> of paracetamol for the treatment of acute low back pain, 4g of paracetamol daily was found to be no more effective than placebo. </p>
<p>In both studies, active and placebo treatments had similarly low rates of side-effects. </p>
<h2>More placebo, please</h2>
<p>This isn’t a good situation, but the placebo effect itself is often overlooked or treated with disdain. Which is a pity – it could be better employed in the fight against pain. <a href="https://www.ncbi.nlm.nih.gov/pubmed/12406519">A 2002 review</a> of placebo effects in clinical pain killer trials concluded: </p>
<blockquote>
<p>If the factors that contribute to placebo analgesia are identified, they could be optimised in clinical practice whereby the general effectiveness of pain treatments could be enhanced.</p>
</blockquote>
<p>And placebo effects were greater when studies specifically tried to investigate how placebos work. In another context, a <a href="https://www.ncbi.nlm.nih.gov/pubmed/19246102">2009 meta-analysis of anti-depressant trials</a> concluded: </p>
<blockquote>
<p>The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power.</p>
</blockquote>
<p>Patient demand for pain relief in the UK is clear, around <a href="http://www.pagb.co.uk/consumer-healthcare-industry/">£575m a year is spent on OTC analgesics</a> and another £567m on analgesics prescribed in <a href="http://content.digital.nhs.uk/catalogue/PUB20200/pres-cost-anal-eng-2015-rep.pdf">primary care</a>. The primary care spend includes £90m on products that could be bought OTC and £115m on compound painkillers that are the next step up the pain ladder. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=318&fit=crop&dpr=1 600w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=318&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=318&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=400&fit=crop&dpr=1 754w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=400&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/154036/original/image-20170124-455-1bs097w.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=400&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">It could all be in the mind.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hand-man-holding-paracetamol-pill-tablet-525244381?src=IPwPgPK4D9nnVUMq0XwMew-1-7">Shutterstock</a></span>
</figcaption>
</figure>
<p>Indeed, people may be willing to pay significant sums for pain relief, which is a measure of economic benefit – a few pounds to relieve everyday pain, tens of pounds to relieve post-operative pain, and hundreds of pounds to relieve chronic pain. </p>
<p>But the current supermarket price for paracetamol is little more than 1p per tablet – and stronger painkillers use codeine and related drugs, which significantly increase the risk of harmful side-effects. </p>
<p>For acute pain, simple safe painkillers are cheap (it’s certainly worth <a href="https://theconversation.com/why-do-people-choose-expensive-branded-drugs-over-cheap-generics-52461">buying generic</a> rather than more expensive branded varieties) and promote active self-management of minor ailments. They may also help to engage the placebo effect. The evidence for effectiveness beyond the placebo effect is mixed (as the Cochrane reviews demonstrate), but doing something <a href="http://www.nhs.uk/Conditions/Back-pain/Pages/Treatment.aspx">does have an effect</a> and painkillers may actively help in some cases. </p>
<p>When people buy these painkillers, they also save the NHS – and taxpayers – the expense of visiting a doctor and having them prescribed. Generic paracetamol costs 19-30p for 16 in the supermarket and 35p on prescription. However, consultation and dispensing costs are considerable.</p>
<p>The spend on OTC painkillers might therefore be like buying a lottery ticket – they will work really well for some people, and rather less well for others. Either way, the losses are insignificant. If there’s a chance that they’ll work for you, then it’s a small price to pay.</p>
<h2>The bigger picture</h2>
<p>Nevertheless, non-pharmacological actions (for example, rest, fluids, change in activities) are equally or more helpful than painkillers <a href="http://www.nhs.uk/conditions/Headache/Pages/Introduction.aspx">in many cases</a>. So people should buy, obtain or use their painkillers in a supportive environment. For example, non-branded medicines are nearly as cheap in pharmacies as supermarkets, and your pharmacist should be able to talk you through the options and offer other advice, too. Doctors, meanwhile, need more time to explore problems with patients and shouldn’t need to write prescriptions to signal the end of a consultation. Their time could be better spent.</p>
<p>Imagine there was enough evidence to ban the OTC sale and prescription supply of simple painkillers. The supply of tea and sympathy would certainly have to increase. It is likely that the demand for compound pain killers or untested treatments would also increase, which risks more serious harm. There would also likely be an increase in visits to the doctor.</p>
<p>A goal to reduce the use of ineffective medicines is desirable. But we must also consider the alternatives and consequences. The treatment of pain isn’t the only area of clinical practice where hope is maximised over effectiveness. Improving the safety and effectiveness of chronic pain relief is a higher priority than reducing acute painkiller consumption. For now, people will keep using cheap (perhaps even quite expensive) OTC painkillers – and it’s hard to say they’re acting irrationally.</p><img src="https://counter.theconversation.com/content/71433/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jonathan Silcock receives funding from the National Institute for Health Research. He provides advice to Health Education England about pharmacy training reforms. He is a member of the Royal Pharmaceutical Society. </span></em></p>They’re often no more effective than placebo, but that shouldn’t necessarily stop us using them.Jonathan Silcock, Senior Lecturer in Pharmacy Practice, University of BradfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/410352015-12-15T19:35:33Z2015-12-15T19:35:33ZWhy different painkillers are only effective for certain types of pain<figure><img src="https://images.theconversation.com/files/101801/original/image-20151113-10420-4um468.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">What type of painkiller matches my pain?</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/melodramababs/3722236413/in/photolist-6EVrcT-68rkQS-4Uoq59-4M3Cn2-97Aug6-bNHXZF-3DEYDL-cbZYq5-cbZQQS-4VdehQ-8BmCw2-bB2F12-4DZiWV-4pxopc-3ijAm-5F9CU8-5cYgUZ-4wrEZt-fC7H4-65q7uB-dpph-B56Cm-7gkikj-7PBwgp-5HpngX-qcvsTe-BASRJ-9i1CNK-fzaB7z-21jc4S-fevCru-8L9YJc-7SaY4K-rEum2W-vmJUA-p4Gxzt-4CVbzC-oSu3H-f8p7k-71XKB7-pHdVCU-jkBSdF-zJh5Wb-p4GwPv-tWD8gn-3KxyJp-6QtPw-6QtNt-ooq8zC-8pgLqs">Nathalie Babineau-Griffiths/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>Whether it’s your head, tooth or back, when you’re in pain, it’s hard to think about anything else. If it’s not too strong, some can ride it out. But in many cases, the pain just gets worse and won’t go away until you take something.</p>
<p>Medicines that kill pain are called analgesics and they vary in how they work. No single painkiller can relieve all types of pain. Those that work for mild pain usually have little effect on severe pain unless combined with a stronger painkiller. </p>
<p>If you want to effectively control your pain, you will need to match your medication to its type and severity.</p>
<iframe src="https://charts.datawrapper.de/J2Llk/index.html" frameborder="0" allowtransparency="true" allowfullscreen="allowfullscreen" webkitallowfullscreen="webkitallowfullscreen" mozallowfullscreen="mozallowfullscreen" oallowfullscreen="oallowfullscreen" msallowfullscreen="msallowfullscreen" width="100%" height="400"></iframe>
<h2>Nociceptive pain</h2>
<p>Nociceptive pain is caused by damage to body tissue. If the pain is mild, such as a headache or a sprained ankle, commonly used over-the-counter <a href="http://www.healthdirect.gov.au/pain-relief-medicines">painkillers are effective</a>. These include tablets containing paracetamol (Panadol), aspirin, or non steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Nurofen). </p>
<p><a href="https://www.bookdepository.com/Pain/9780702034787">Paracetamol</a> helps to dampen pain signals to the brain. NSAIDs inhibit the activity of the enzymes that lead to pain, inflammation and fever being produced in the body.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=441&fit=crop&dpr=1 600w, https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=441&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=441&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=555&fit=crop&dpr=1 754w, https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=555&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/97522/original/image-20151007-7363-k527ww.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=555&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">If you want to control your pain, you will need to match your medication to its type and severity.</span>
<span class="attribution"><span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>Combination tablets, which have a small dose of codeine plus paracetamol, aspirin or ibuprofen, can be used to treat moderate pain. In Australia, you can buy these kinds of painkillers only in a pharmacy. Those sold over the counter have brand names such as Panadeine, Aspalgin and Nurofen Plus. </p>
<p>The government <a href="http://www.news.com.au/lifestyle/health/health-problems/codeine-counter-ban-sparks-anger/news-story/2aeb86fbf89e3669cda43df13af38d9e">recently announced</a> it will make any medication containing codeine available only with a prescription from mid-2016. </p>
<p>It is important to remember the maximum adult dosage for paracetamol is four grams (eight tablets) per day. Taking more than the recommended dose can cause damage to your liver. </p>
<p>Painkillers typically prescribed by a doctor to relieve acute to moderate pain are codeine together with paracetamol tablets (Panadeine Forte) and tramadol tablets, which are opioid pain killers.</p>
<p>The severe pain you experience following a broken bone or an operation usually needs strong painkillers that your doctor would prescribe. This may be morphine given as a tablet or by injection.</p>
<p>Morphine-like medicines relieve pain by <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698859/">interacting with specific proteins</a> called opioid receptors, which are located in the brain, spinal cord and other parts of the body. These opioid receptors are the same ones the body’s own natural pain-killer molecules, called endorphins, use.</p>
<h2>Neuropathic pain</h2>
<p>Neuropathic pain is pain caused by damage to the nerves. Painkillers such as morphine, NSAIDs and paracetamol that are effective for the relief of nociceptive and inflammatory pain conditions are not effective for the relief of neuropathic pain.</p>
<p>This is because the underlying mechanisms that cause neuropathic pain following nerve injury are different from those that induce nociceptive and acute inflammatory pain.</p>
<p>Medications originally developed to treat depression and epilepsy are <a href="http://www.cpmc.org/professionals/research/about/news/neuropathic-pain-treatment.html.">recommended</a> as first-line treatments for the relief of neuropathic pain. </p>
<p>Antidepressants alleviate neuropathic pain by boosting the body’s own pain-fighting pathways. This includes boosting signalling in the brain which inhibits pain-signalling at the level of the spinal cord. The detailed mechanisms by which anti-epileptic drugs alleviate neuropathic pain are diverse but the net effect is to dampen pain signals. </p>
<h2>Migraine pain</h2>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=902&fit=crop&dpr=1 600w, https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=902&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=902&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1134&fit=crop&dpr=1 754w, https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1134&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/101800/original/image-20151113-12370-1p26f75.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1134&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Paracetemol is an effective painkiller for mild pain.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/comedynose/5094174927/in/photolist-3kA6mu-c56Zk-8L9YJc-C3kNp-2WbJTr-afoP1F-4koqVM-5jM5wY-6VrLiq-5hZttP-bWo4cE-97pDG4-4oMWi1-5PbnGk-e7dkne-bbRgQz-46RVe">Pete/Flickr</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Migraine is a particularly debilitating type of pain. It is often accompanied by nausea, vomiting and sensitivity to light and sound. It can last for a few hours or several days.</p>
<p>Migraine affects about <a href="http://headacheaustralia.org.au/migraine">12% of Australians</a>. Some experience auras such as flashing lights or changes in smell perception, which can serve as early warning signs the migraine is coming.</p>
<p>If painkillers such as paracetamol, aspirin, ibuprofen or ergotamine (made specifically to relieve migraine by narrowing blood vessels in the brain) are taken at the onset of the aura, the migraine can often be stopped or its severity reduced. For those suffering a severe migraine attack, prescription medications known as triptans can be effective treatments by reversing the brain blood vessel dilation.</p>
<h2>Chronic inflammatory pain</h2>
<p>Chronic pain affects up to <a href="http://www.painaustralia.org.au/healthcare-professionals/patient-resources.html">one in five</a> adults. One of the most common is pain from osteoarthritis, the most common type of arthritis.</p>
<p>Osteoarthritis pain is a chronic inflammatory pain caused by arthritic joint disease, typically in the knee or hip. As the joint cartilage and underlying bone break down, the joint becomes inflamed and this triggers the pain. The first-line painkiller for osteoarthritis pain is paracetamol.</p>
<p>For people with more severe pain, NSAIDs such as naproxen may be more effective. But <a href="https://theconversation.com/do-you-need-to-take-some-painkillers-with-food-to-protect-your-stomach-47156">chronic use of these</a> is associated with an increased risk of side effects, especially <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/medications-non-steroidal-anti-inflammatory-drugs">bleeding and ulceration</a> of the stomach lining. Less commonly, morphine or strong morphine-like analgesics are prescribed. </p>
<h2>Cancer pain</h2>
<p>Most cancer pain is caused by the tumour pressing on bones, nerves or other organs in your body. Pain can also be caused by the cancer treatment such as chemotherapy or radiotherapy. Oral morphine-like analgesics taken regularly, often in combination with paracetamol, are prescribed for moderate to severe chronic cancer pain. </p>
<p>Although drowsiness usually occurs at the start of treatment or after a dosage increase, this typically reduces after a couple of weeks. Anti-nausea and laxative agents are given at the beginning of treatment to minimise the side effects of nausea, vomiting and constipation. Nausea usually lasts no more than two to three weeks. </p>
<p>However, as constipation persists, it is very important that laxative use is maintained. For cancer pain involving nerve impingement, your doctor will add a prescription painkiller for neuropathic pain.</p>
<hr>
<p><em>This article is part of a series focusing on Pain. Read other articles in the series <a href="https://theconversation.com/au/topics/pain-series">here</a>.</em></p><img src="https://counter.theconversation.com/content/41035/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Maree Smith currently holds competitive research grant funding from the Australian Research Council in collaboration with Boehringer Ingelheim GmbH, from the National Health and Medical Research Council and from The University of Queensland (CIEF grant) in collaboration with Que Oncology. Maree Smith is named inventor on patented AT2 receptor antagonist technology for the relief of neuropathic and chronic inflammatory pain, commercialized by the UQ spin-out company, Spinifex Pharmaceuticals (2005-2015), that was acquired by Novartis in mid-2015. Maree Smith conducts contract R&D studies for a large number of companies in her role as Executive Director of the Centre for Integrated Preclinical Drug Development at The University of Queensland. She is currently President and Board member of the Australian Pain Relief Association (APRA) and she is a member of the Editorial Board of Pain: Clinical Updates.</span></em></p>When you’re in pain, it’s hard to think about anything else. In many cases, it won’t go away until you take something for it, but how do you know what type and strength to take?Maree Smith, Executive Director, Centre for Integrated Preclinical Drug Development and Professor of Pharmacy, The University of QueenslandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/460572015-08-13T18:29:35Z2015-08-13T18:29:35ZResearchers produce opioid pain killer from genetically modified yeast with opium poppy genes<figure><img src="https://images.theconversation.com/files/91759/original/image-20150813-21398-1m6h9gw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">But not defunct just yet.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/79818573@N04/19085516479/in/photolist-v5wg7X-rXF6tg-tyvLqT-9uJQV4-8cYaqK-bXarYn-nRrZnd-f5MPKA-ccdj2m-cgNTTf-7YNGtT-7YRWEh-7YRVbh-7YNJpP-7YRWms-7YRW2u-7YRXXj-7YRX7d-2ctBe4-8kZNdM-bd462x-bd46eB-9VKkgV-9X8Chb-eBpY9x-2JUkT-6gJYB4-rsZskN-5u7YNX-r6Yb6B-qCgr1N-rUwCgE-scQjpw-sRvGzH-qP77Qm-rhFMMs-rijAiK-rXwWrJ-rtxccq-syUotb-sRkFXB-szidiX-sMkqK1-tuA9Z1-ttWAnR-sf8jhv-rXy8v7-sPrP6E-kAckuh-kAaz3x">free photos</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span></figcaption></figure><p>The natural world has long been a source of useful compounds. Aspirin, quinine and morphine all have beneficial therapeutic properties and are often found in plants. Being able to identify, extract and synthesise biologically active ingredients can lead to larger, cheaper amounts being produced. </p>
<p>For compounds with relatively simple chemical structures, such as aspirin, this is straightforward. Others with more complex structures such as opioids – the family of medicines that includes morphine and codeine – it’s extremely difficult.</p>
<p>The complexity of opioids means their active compounds are still sourced from the opium poppy. But now researchers at Stanford have cleverly used genetically modified baker’s yeast to convert sugar into an opioid called hydrocodone. In a <a href="http://www.sciencemag.org/content/early/2015/08/12/science.aac9373">study published in Science</a>, a second strain also produced thebaine, a precursor to other opioids.</p>
<p>In nature, the opium poppy has enzymes that are able to synthesise complex molecule structures in a cell. By reprogramming their genetic machinery, the researchers were able to mimic this process in yeast cells, with the added advantage that it also speeded up the process. While production using plans could take up to a year from farm to factory, the Stanford researchers claim a speed of three to five days. Although still in very minute amounts, their proof of concept has the potential for a much wider impact in synthesising other structurally complicated molecules. </p>
<h2>Finding active compounds</h2>
<p>Biologically active compounds are produced by living organisms in tiny amounts as part of their normal life; that they may have a beneficial effect on us is a side effect but one we have exploited through the ages. The challenge for the chemist is not only to isolate these useful compounds but to obtain a useful amount. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91754/original/image-20150813-21435-iqgxnv.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Pacific yew – useful in large amounts.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:PacificYew_7591.jpg#/media/File:PacificYew_7591.jpg">Wsiegmund</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>A single plant, for example, only makes microgram quantities of a bioactive compound either because the effect of the molecule on the plant is so potent that a small amount is required by the plant or because it’s a byproduct that the plant doesn’t need. For example a Pacific yew tree only produces minute amounts of taxol, thought to play an antifungal role in protecting the tree. However, for us, taxol has been <a href="http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Chemotherapy/Individualdrugs/Paclitaxel.aspx">shown to treat a range of cancers</a>. To obtain enough taxol to produce a dose to treat cancer in us would require several hundred yew trees. So once the compound has been isolated and its structure determined, more of it can be synthesised in the laboratory. </p>
<h2>Creating a chemical factory</h2>
<p>Many biologically active compounds are the result of a complex series of reactions occurring within cells and driven by nature’s own chemical reagents – enzymes. These naturally occurring proteins are produced within cells encoded by their DNA and allow quite lengthy and complex biosynthesis to be carried out and allows a cell to synthesise complex compounds such as opioids efficiently. </p>
<p>In the lab it can involve as many as 20 or 30 chemical reactions each with a separation and purification step to replicate this – so you can see why it is so hard to scale up to produce useful, cheaper amounts of the compound. </p>
<p>The ability of enzymes to carry out chemical reactions with high degrees of selectivity and efficiency have made them useful chemical tools. This efficiency comes at a price though as, outside their cell the reactivity of enzymes can be drastically reduced. It is much better to keep them inside the cell. The trouble is that no single organism will have all the enzymes you need to carry out a lengthy chemical synthesis.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=800&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=800&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=800&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1005&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1005&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91755/original/image-20150813-21398-n4jcy.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1005&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Everyday yeast.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:%D0%94%D1%80%D0%BE%D0%B6%D0%B6%D0%B8_%D1%81%D1%83%D1%85%D0%B8%D0%B5_%D0%B0%D0%BA%D1%82%D0%B8%D0%B2%D0%BD%D1%8B%D0%B5_-_Active_dry_yeast.JPG">Shliphmash</a></span>
</figcaption>
</figure>
<p>Yeast has always been a good chemical factory and our long experience over several thousand years in handling it to make bread and alcoholic drinks have given us a good understanding of how it carries out simple reactions such as making sugars into alcohol. It’s a relatively simple organism compared to a poppy plant but the sequencing of its entire genome in 1996 offered a means of rewriting yeast’s DNA and increasing the number of reactions it could process. </p>
<p>To allow yeast cells to produce more complex molecules, however, it needs more enzymes to work with. To do this you need to tack the machinery to produce enzymes onto yeast cells by reprogramming its DNA to tell it how to make the enzymes it needs. </p>
<p>In their work, the Stanford group took more than 20 genes from five different organisms – the California poppy, rat, goldthread, bacteria, and opium poppy – and engineered them into the yeast genome to create the conditions to make hydrocodone, all without disabling the yeast cell. This is an impressive achievement in itself, as putting these different enzymes together in such a sequence runs the risk of a product of one enzyme reaction poisoning or inhibiting another crucial enzyme in the sequence.</p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=493&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=493&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91771/original/image-20150813-21401-1qsjek6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=493&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Setting up the production line.</span>
<span class="attribution"><span class="source">Stephanie Galanie, Smolke Lab</span></span>
</figcaption>
</figure>
<h2>A question of scale</h2>
<p>The research gives us another way to synthesise natural products, which sits between a purely lab-based and wholly natural approach to producing compounds. However, despite the proof of concept, the researchers still have the same problem with plant sources. The yields per yeast are still too low to be useful (they say it will still take it would take more 16,000 litres of bioengineered yeast to produce a single dose of pain relief). This is partially offset by the shorter production times as yeast cultures can be grown and harvested in a matter of days as opposed to a longer annual growing cycle for plants. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/91757/original/image-20150813-21398-jct93k.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">The old fashioned way.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/beggs/6588916229/in/photolist-b3eVeX-9UbqNs-9Ubd4q-8jXCWt-6R9n3Q-nqeFwf-o7wBhX-6R9o5o-6R5iVe-6R5j8a-6R5gYX-6R5f36-6R5jHK-6R5fNR-6R9nuY-6R5izX-6R5ioX-6R9iyb-6R9mom-6R5jyX-opSn4X-fg5z49-WnVfC-hSbTN-dyuKAh-cppJ79-51tis5-oNSY3o-8QY91R-8QY8fe-axC8sY-6FpsCV-4XhPTM-4XJsbd-7gxJ5z-7RHVYS-5CmtPF-9sqyyv-8QYe3v-6rf26j-bXarYn-6gmoXm-7CsaDc-9GcxM-o7gdpe-4Xmfb6-7yx4gL-agLL58-9FX6QN-7RCuNQ">Brian Jeffery Beggerly</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>Given the number of genes they’ve been able to incorporate into the yeast cells, an increase in efficiency is certainly not impossible. There is no question that yeast cells have the potential to be chemical factories taking in simple chemical feedstock and producing complex useful compounds efficiently and specifically.</p>
<p>Synthesising a complex molecule in the laboratory is a satisfying exercise for a chemist but as the Stanford researchers pointed out, many of these syntheses are impractical to scale up. Their approach was focused on the end product rather than the practicality of the synthesis itself. To have real-life application, we now need to find a way to scale up the process.</p><img src="https://counter.theconversation.com/content/46057/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>James Bruce receives funding from EPSRC, The Nuffield Foundation, The Wellcome Trust Innovate UK and GSK. He is a member of the Royal Society of Chemistry.</span></em></p>Yeast can produce opioid from sugar but although a proof of concept, we’re still far away from production at scale.James Bruce, Senior Lecturer in Organic Chemistry, The Open UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/324812014-11-14T10:56:34Z2014-11-14T10:56:34ZExplainer: naloxone, the antidote to opioid overdose<p>Many first responders’ – even some university police officers – are carrying a new tool in their first-aid kits. It’s naloxone, the opioid overdose antidote drug, and today it’s more widely available than ever. Naxolone can seem like a miracle drug when administered to an OD'ing patient. How does it work? </p>
<p>In the US, we are facing an opioid and chronic pain epidemic. Opioid prescriptions have <a href="http://www.drugabuse.gov/about-nida/noras-blog/2014/09/opioids-chronic-pain-gap-in-our-knowledge">increased 300%</a> over the past 20 years with opioid overdose deaths <a href="http://www.nejm.org/doi/full/10.1056/NEJMp1402780#t=article">quadrupled</a> in parallel. The latest data from the Centers for Disease Control and Prevention (CDC) tell us that prescription opioids – pain relievers like morphine, methadone, hydromorphine, fentanyl, oxycodone, hydrocodone – were responsible for <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6326a2.htm">16,917 overdose deaths</a> in 2011, and deaths from heroin <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6327a5.htm">doubled</a> from 2,089 in 2002 to 4,397 in 2011. More recently CDC reported that in 28 states death rate for heroin <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6339a1.htm?s_cid=mm6339a1_w">doubled</a> from 2010-2012 with a small decline in deaths from opioid pain relievers.</p>
<p>High doses of opioids put the breathing center in the brain to sleep, leading to loss of consciousness. Breathing slows and then stops. In use since the 1970s, naloxone saves lives by quickly reversing these deadly effects. As </p>
<h2>Opioids mimic natural neurotransmitters</h2>
<p>Opioids are powerful chemicals. On the one hand they can relieve pain and suffering, while on the other they can cause tragedy. Opioid drugs reduce the perception of pain and stimulate pleasure and a sense of well-being.</p>
<p>Opioids are effective because they resemble a type of chemical messenger naturally found in the brain and spinal cord. These neurotransmitters, called endorphins and encephalins, do two things. They block pain transmission by binding to the opioid receptors of specialized nerve cells, and they promote euphoria by binding to cells in the reward center of brain. </p>
<h2>This is your brain during opioid overdose</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=407&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=407&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=407&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=512&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=512&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61195/original/h8sv326j-1412797563.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=512&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption"></span>
<span class="attribution"><a class="source" href="http://harmreduction.org/issues/overdose-prevention/overview/overdose-basics/understanding-naloxone/">Maya Doe-Simkins/Harm Reduction Coalition</a>, <span class="license">Author provided</span></span>
</figcaption>
</figure>
<p>When external opioids are taken in too large amounts, receptors are overwhelmed in the part of the brain that controls breathing, an area called the medulla oblongata. Breathing slows down to a critical level and then stops. Death follows.</p>
<p>Signs of an overdose include pinpoint pupils, pale skin, limpness, lack of response to painful stimuli and slow pulse and breathing. As the overdose progresses, fingernails and lips may be blue and skin becomes blue or ashen. Breathing sounds like snoring or gurgling and then ceases. Within a short period, the heart may stop pumping blood. After about five minutes starved of blood, serious damage to the brain, heart and other organs occurs. </p>
<h2>Naloxone works its magic</h2>
<p>Naloxone is an antagonist to opioids; it counteracts them by blocking receptors. Commonly known by its trade name, Narcan, it can be injected into the vein (IV) or muscles (IM), or sprayed intra-nasally (IN). It can even be self-injected intramuscularly or subcutaneously using the recently-FDA-approved <a href="http://evzio.com/patient/?gclid=CIWYorfGncECFcpr7Aod2DAAcA">Evzio</a>, a delivery system with voice instructions that is marketed to opioid users and their social network themselves.</p>
<p>Naloxone passes into the blood stream and travels to the medulla oblongata. Naloxone’s chemical shape is a perfect match for the brain’s opioid receptors. In fact, it has an even greater affinity for these receptor sites than the opioids themselves do. So when naloxone hits the brain, it competes and shoves loose the opioids that are suppressing breathing. Usually within a few minutes breathing is restored.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/Uq6AxrEY3Vk?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
</figure>
<p>After administration of naloxone doses ranging from 0.2mg to 2mg there is a dramatic restoration of vital signs and reanimation. Patients seem to miraculously come back to life, sometimes jumping up off the stretcher in the ER, as if nothing had ever happened. Patients who had been on the brink of death can be upset that they were given naloxone and want to be discharged. Since naloxone triggers withdrawal, individuals often awaken abruptly and agitated. This effect is more common with the IV formulation than the intra-nasal version. Another advantage of the nasal spray is the avoidance of a needle stick.</p>
<p>The effect of naloxone peaks within two to five minutes and lasts from 30 to 90 minutes. It is important that medical assistance is summoned when naloxone is used, because a positive response may be short lived. Many opioids – like methadone, extended release oxycodone (oxycontin) and hydrocodone (zohydra) – are longer acting and may require repeated or increase doses of naloxone. And many opioid overdoses <a href="http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a1.htm">involve alcohol and other drugs</a> that are not responsive to naloxone. These instances in which naloxone may not work immediately or fails to reverse an overdose require that bystanders institute rescue breathing and call a universal access number such as 911 for medical assistance. </p>
<h2>Distributing naloxone</h2>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/61190/original/cncfr37c-1412786493.JPG?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Opioid antidote.</span>
<span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Naloxone_(1).JPG">Intropin</a>, <a class="license" href="http://creativecommons.org/licenses/by/4.0/">CC BY</a></span>
</figcaption>
</figure>
<p>There’s currently a major effort to put naloxone in the hands of first responders: EMTs, police and firefighters, and the lay public. <a href="https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf">As of August 2014</a>, 25 US states and the District of Columbia have amended their laws to allow physicians to prescribe and dispense the drug and to allow the lay public to administer naloxone without legal consequence. Twenty states and DC have amended or enacted Good Samaritan Laws to allow bystanders to summon medical assistance without legal repercussions.</p><img src="https://counter.theconversation.com/content/32481/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Edward Bernstein 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>Many first responders’ – even some university police officers – are carrying a new tool in their first-aid kits. It’s naloxone, the opioid overdose antidote drug, and today it’s more widely available than…Edward Bernstein, Professor of Emergency Medicine and Community Health Sciences, Boston UniversityLicensed as Creative Commons – attribution, no derivatives.