health – Sam Miner – Medium

A battle against the opioid crisis is taking place in research laboratories across the world. With annual deaths due to opioid overdose approaching 50,000 in the U.S alone, research into ways to counter this epidemic has taken on greater importance. One way to lower the number of overdoses would be to replace prescribing opioids with new pain treatments.

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Using modern genome mapping technologies, some researchers hope to find new pain treatments by investigating the genomes’ of individuals who naturally experience little or no pain in their own lives. While current pain treatment often relies on opioid receptors, opioids are both highly addictive and frequently lethal in cases of overdose. New treatments would give clinicians and patients options to avoid opioids.

Jo Cameron, a 71-year-old Scottish woman, is one fascinating example of an individual who experiences very little in the way of pain. Doctors were first clued in to her lack of pain following hand surgery when she declined pain medication. As they searched her medical history, they found more evidence of a lifetime without pain.

A few years prior to the hand surgery, she had undergone a hip replacement surgery. In her case, osteoarthritis had degenerated her hip without her feeling the normally pain warning signs. Again, her post-op care hadn’t required pain medication. Oral surgeries- same pain free experience. To Jo Cameron, her pain experience, or lack thereof, seemed the norm. So much so, that her experience giving birth without an epidural led her to believe friends had been exaggerating about the pain.

Jo Cameron’s seeming immunity to pain during childbirth and following multiple surgeries has led to research recently published in the British Journal of Anesthesia. Researchers have mapped her genome in search of the cause of her pain-free condition. If Ms. Cameron can avoid pain without the use of medication, by identifying the cause, researchers hope to find new methods of treating pain. In the case of Ms. Cameron, mutations in a pair of related genes (FAAH and FAAH-OUT) have been identified as the genetic basis for her condition.

In most individuals, the FAAH gene remains active and is involved in the breakdown of biologically active molecules that are naturally produced by the body and mimic the role of opioids to lessen pain. In Jo Cameron’s case, it appears that her FAAH and FAAH-OUT mutations have led to decreased FAAH activity. Reduced activity of the FAAH gene means she possesses a higher level of natural pain killers. The authors of this study note that decreasing the activity of FAAH may then be a promising path for future clinical research on pain.

Another interesting outcome of the research into Jo Cameron is the possible application of her case to forms of psychological pain. In addition to her decreased physical pain, Ms. Cameron’s response to questionnaires has suggested she experiences little to no anxiety or depression and has no memory of ever experiencing strong feelings of either.

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Historically, there have been many known cases of pain insensitivity, grouped under the condition known as Congenital Insensitivity to Pain and Anhidrosis (CIPA). However, CIPA has always been recognized as an extreme condition. Caused by a deficiency in proper nerve growth it represents a non-reversible ability to feel pain even when pain would serve as a useful indicator of harm. CIPA patients have always been susceptible to unintentional self-harm like scratching their cornea, and can suffer lasting bone and joint deformities caused by unrealized injuries.

Today, with the capabilities to map individual genomes, researchers can identify and study new causes of decreased pain outside of CIPA. Those cases, like Jo Cameron’s, can be less extreme than the loss of nerve growth seen in CIPA. These investigations into the genetic bases of pain have given researchers hope for many new targets in pain treatment.

Recently, researchers were able to map the genome of an entire family with decreased pain sensitivity. The research, published in the journal Brain, highlights how many new targets for investigation can be exposed through this type of genetic research. In this case, the heightened pain tolerance of the family members was due to a shared mutation in the ZFHX2 gene. Previous research has shown the ZFHX2 gene is involved in activating other genes, meaning the cause of decreased pain, in this family’s case, is more complicated than one gene and one mutation. As the authors of this study point out, this research could implicate several new targets for pain therapy– ZFHX2 and its targets.

As more people with high pain tolerance are identified and studied, researchers remain optimistic about finding new methods to treat pain. If new treatments are discovered, there could be a paradigm shift in the way the medical field approaches pain treatment. Instead of the currently limited options to treat pain, multiple new ones could be employed. Less addictive medications and new options for individuals addicted to current forms of pain medication would go a long way towards fighting the opioid crisis. As researchers continue to study individuals with abnormally high pain tolerance, hopefully they can give individuals a new way to avoid pain and society a new way to combat addiction.

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