{"id":143077,"date":"2018-10-26T08:58:15","date_gmt":"2018-10-26T12:58:15","guid":{"rendered":"https:\/\/today.uconn.edu\/?p=143077"},"modified":"2018-10-26T11:55:28","modified_gmt":"2018-10-26T15:55:28","slug":"people-hurt-others","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2018\/10\/people-hurt-others\/","title":{"rendered":"Why Do Some People Hurt More Than Others?"},"content":{"rendered":"

Anyone who came of age in the 1990s remembers the \u201cFriends\u201d episode where Phoebe and Rachel venture out to get tattoos. Spoiler alert: Rachel gets a tattoo and Phoebe ends up with a black ink dot because she couldn\u2019t take the pain. This sitcom storyline is funny, but it also simply illustrates the question that I and many others in the field\u00a0of<\/a>\u00a0\u201cpain<\/a>\u00a0genetics<\/a>\u201d\u00a0are<\/a> trying<\/a>\u00a0to<\/a>\u00a0answer<\/a>. What is it about Rachel that makes her different from Phoebe? And, more importantly, can we harness this difference to help the \u201cPhoebes\u201d of the world suffer less by making them more like the \u201cRachels\u201d?<\/p>\n

Pain is the single most common symptom reported when seeking medical attention. Under normal circumstances, pain signals injury, and the natural response is to protect ourselves until we have recovered and the pain subsides. Unfortunately,\u00a0people differ not only in their ability to detect, tolerate, and respond to pain<\/a>\u00a0but also in how they report it and how they respond to various treatments. This makes it difficult to know how to effectively treat each patient. So, why isn\u2019t pain the same in everyone?<\/p>\n

Individual differences in health outcomes often result from complex interactions of psychosocial, environmental, and genetic factors. While pain may not register as a traditional disease like heart disease or diabetes, the same constellation of factors are at play. The painful experiences throughout our lifetime occur against a background of genes that make us more or less sensitive to pain. But our mental and physical state, previous experiences \u2013 painful, traumatic \u2013 and the environment can modulate our responses.<\/p>\n

If we can better understand what makes individuals more or less sensitive to pain in all kinds of situations, then we are that much closer to reducing human suffering by developing targeted personalized pain treatments with lower risks of misuse, tolerance and abuse than the current treatments. Ultimately, this would mean knowing who is going to have more pain or need more pain-killing drugs, and then being able to effectively manage that pain so the patient is more comfortable and has a quicker recovery.<\/p>\n

Not all pain genes are the same<\/strong><\/p>\n

With the sequencing of the human genome, we know a lot about the number and location of genes that make up our DNA code. Millions of small variations within those genes have also been identified, some that have known effects and some that don\u2019t.<\/p>\n

These variations can come in a number of forms, but the most common variation is the\u00a0single nucleotide polymorphism<\/a>\u00a0\u2013 SNP, pronounced \u201csnip\u201d \u2013 representing a single difference in the individual units that make up DNA.<\/p>\n

There are approximately 10 million known SNPs in the human genome; an individual\u2019s combination of SNPs makes up his or her personal DNA code and differentiates it from that of others. When a SNP is common, it is referred to as a variant; when a SNP is rare\u00a0\u2013 found in less than 1 percent of the population\u00a0\u2013 then it is called a mutation. Rapidly expanding evidence implicates\u00a0dozens of genes<\/a>\u00a0and variants in determining our pain sensitivity, how well analgesics \u2013 like opioids \u2013 reduce our pain and even our risk for developing chronic pain.<\/p>\n

A history of pain tolerance<\/strong><\/p>\n

The first studies of \u201cpain genetics\u201d were of families with an extremely rare condition characterized by the absence of pain. The first report of\u00a0congenital insensitivity to pain<\/a>\u00a0described \u201cpure analgesia\u201d in a performer working in a traveling show as \u201cThe Human Pincushion.\u201d In the\u00a01960s,<\/a>\u00a0there were\u00a0reports<\/a>\u00a0of\u00a0genetically<\/a>\u00a0related families with children who were pain-tolerant.<\/p>\n

\"\"
Teacher\u2019s aide Sue Price, right, examines Ashlyn Blocker\u2019s head for scrapes, after she bumped it after school. Ashlyn never complains because the 5-year-old is among a small number of people in the world known to have congenital insensitivity to pain \u2013 a rare genetic disorder that makes her unable to feel pain.<\/span>\u00a0AP Photo\/Stephen Morton<\/a><\/span><\/figcaption><\/figure>\n

At that time, the technology did not exist to determine the cause of this disorder, but from these rare families we know that CIP \u2013 now known by wonkier names like Channelopathy-associated insensitivity to pain and Hereditary Sensory and Autonomic Neuropathy \u2013 is the result of specific mutations or deletions within single genes required for transmitting pain signals.<\/p>\n

The most common culprit is one of a small number of SNPs within SCN9A, a gene that encodes a protein channel necessary for sending pain signals. This condition is rare; only a handful of cases have been documented in the United States. While it might seem like a blessing to live without pain, these families must always be on alert for severe injuries or fatal illnesses. Typically children fall down and cry, but in this case, there\u2019s no pain to differentiate between a scraped knee and a broken knee cap. Pain insensitivity means that there is no chest pain signaling a heart attack, and no lower right abdominal pain hinting at appendicitis, so these can kill before anyone knows that there is something wrong.<\/p>\n

Supersensitivity to pain<\/strong><\/p>\n

Variations within SCN9A not only cause pain insensitivity, but have also been shown to trigger two severe conditions characterized by extreme pain: primary erythermalgia and paroxysmal extreme pain disorder. In these cases, the mutations within SCN9A cause more pain signals than normal.<\/p>\n

These types of heritable pain conditions are extremely rare and, arguably, these studies of profound genetic variations reveal little about more subtle variations that may contribute to individual differences in the normal population.<\/p>\n

However, with the growing public acceptance of genome-based medicine and calls for more precise personalized health care strategies, researchers are translating these findings into personalized pain treatment protocols that match a patient\u2019s genes.<\/p>\n

\"\"
Many of the answers to why pain sensitivity differs from person to person lies in our genes.<\/span>\u00a0Sergei Drozd \/ Shutterstock.com<\/a><\/span><\/figcaption><\/figure>\n

Do genetic variations affect pain in everyone?<\/strong><\/p>\n

We know some of the major genes that influence pain perception, and new genes are being identified all the time.<\/p>\n

The SCN9A gene is a major player in controlling the body\u2019s response to pain by activating or silencing the sodium channel. But whether it amplifies or dampens pain depends on the mutation an individual carries.<\/p>\n

Estimates suggest that up to 60 percent of the variability in pain is the result of inherited \u2013 that is, genetic \u2013 factors. Stated simply, this means that pain sensitivity runs in families through normal genetic inheritance, much like height, hair color, or skin tone.<\/p>\n

Turns out that SCN9A also plays a role in pain in the normal population. A relatively more common SNP within SCN9A, called 3312G>T, which occurs in 5 percent of the population, has been shown to determine sensitivity to\u00a0post-operative pain<\/a>\u00a0and how much opioid medication is needed to control it.\u00a0Another SNP<\/a>\u00a0in SCN9A gene causes greater sensitivity for those with pain caused by osteoarthritis, lumbar disc removal surgery, amputee phantom limbs, and pancreatitis.<\/p>\n

New painkillers from sea creatures<\/strong><\/p>\n

\"\"<\/a><\/p>\n
<\/div>
Pufferfish, like\u00a0Arothron meleagris,<\/em>\u00a0can produce a toxin that works by blocking the transmission of pain signals.<\/span>\u00a0NPS photo – Bill Eichenlaub<\/a><\/span><\/figcaption><\/figure>\n

Therapeutically, we have been using local anesthetics, including lidocaine, to treat pain by inducing a short-term block of the channel to stop pain transmission. These drugs have been continuously used to safely and effectively block pain for more than a century.<\/p>\n

Interestingly, researchers are evaluating tetrodotoxin, a potent neurotoxin produced by sea creatures like pufferfish and octopuses, which works by blocking pain signal transmission, as a potential pain killer. They have shown early efficacy in\u00a0treating cancer pain<\/a>\u00a0and\u00a0migraine<\/a>. These drugs and toxins induce the same state that is present in those with congenital insensitivity to pain.<\/p>\n

If there\u2019s one silver lining to the opioid crisis, it is the realization that we need more precise tools to treat pain \u2013 ones that treat pain at the source and come with fewer side effects and risk. By understanding the genetic contribution to pain sensitivity, susceptibility to chronic pain, and even analgesic response, we can then design treatments that address the \u201cwhy\u201d of pain and not just the \u201cwhere.\u201d We\u2019re beginning to design precision pain management strategies already, and the benefit to humankind will only increase as we know more about why pain differs among people.<\/p>\n

Originally published in The Conversation<\/a>. Erin Young is an assistant professor of nursing and assistant director of the UConn Center for Advancement in Managing Pain<\/a>.<\/em><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

If we can better understand what makes individuals more or less sensitive to pain, then we are that much closer to reducing human suffering, writes Erin Young of Nursing.<\/p>\n","protected":false},"author":76,"featured_media":143081,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[1877,2231,2076,2225],"tags":[],"magazine-issues":[],"coauthors":[175],"class_list":["post-143077","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nur","category-health-well-being","category-research","category-uconn-storrs"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-04-11 06:38:35","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/143077","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/76"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=143077"}],"version-history":[{"count":10,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/143077\/revisions"}],"predecessor-version":[{"id":143109,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/143077\/revisions\/143109"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/143081"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=143077"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=143077"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=143077"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=143077"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=143077"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}