No pain, sane brain: Clues to pain and anxiety treatment

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Jo Cameron, 71, recently discovered that her pain insensitivity was unlike her peers. This is despite the former teacher from Inverness experiencing a sensation as small as a ‘tickle’ during childbirth 40 years ago, believing her peers to have exaggerated the pain. In daily life, she had broken limbs, cuts and burns, and underwent many operations without needing painkillers. More unusually, she’s felt no anxiety. Scoring zero out of 21 on an anxiety test, she claimed she felt cheerful at all times and didn’t feel devastated by a close one’s death nor panicked in the face of danger, such as a traffic accident.

Cameron’s pain insensitivity was first noticed by a surprised consultant, who then referred her to pain specialists in the hopes that researchers would find out the reason for her pain insensitivity. When Cameron was 65, she had an X-Ray for a hip joint degeneration, which she only noticed because it caused her to walk in a lopsided manner. For three years before that, a general practitioner had turned her away because she felt no pain. However, the X-Ray would go onto show that her hip was massively deteriorated. While her hip was being fixed, it was found that her thumbs were also deformed by osteoarthritis. Following this, Cameron, now aged 66, underwent a double hand operation. Despite the operation being a painful procedure for most people, Cameron reported no pain. Surprised, Dr Devjit Srivastava, the consultant overseeing Cameron’s recovery, referred her to pain geneticists at UCL and Oxford University.

The researchers analysed Cameron’s genes and concluded that her pain insensitivity is due to two genetic mutations, which work together to suppress pain and anxiety. The first mutation suppresses the activity of a gene called FAAH, which makes an enzyme that digests anandamide, the protein responsible for pain sensation, mood and memory. People with this mutation, like Cameron, have more anandamide than average. Previous mice studies  showed that mice without FAAH have reduced pain and anxiety, accelerated wound healing, and fear-extinction memory, erasure of fearful memories. This would explain why Cameron feels no pain, is always cheerful and rarely anxious, but also forgetful.

Cameron, now aged 66, underwent a double hand operation. Despite the operation being a painful procedure for most people, Cameron reported no pain. Surprised, Dr Devjit Srivastava, the consultant overseeing Cameron’s recovery, referred her to pain geneticists at UCL and Oxford University

The second mutation, which initially mystified scientists, is a ‘micro-deletion’ of a previously unknown gene, which is now named FAAH-OUT. This means that a chunk of FAAH-OUT gene is chopped off. It is theorised that FAAH-OUT controls the amount of FAAH, and so the second mutation, which disables FAAH-OUT, in turn silences the FAAH gene. As a result, Cameron has twice as much anandamide than the general population.

The second mutation is the more important determinant for whether someone feels pain or not and is the reason why Cameron’s son who has the second mutation and not the first one is numb to pain. The mutation, thus, seems to be genetically inherited.

Interestingly, Cameron’s mother and daughter feel pain normally, so Cameron may have inherited the two mutations from her father. When diagnosed with the two mutations, Cameron realised she wasn’t ‘incredible healthy’ as she had initially believed.

The researchers analysed Cameron’s genes and concluded that her pain insensitivity is due to two genetic mutations, which work together to suppress pain and anxiety

Dr James Cox, one of the lead authors of the study, claimed that understanding how the newly discovered FAAH-OUT gene works can shed light into making effective painkillers. He also said that the FAAH gene was already considered to be “a possible target for pain and anxiety treatments,” which this study affirms. He added, “We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety, and potentially chronic pain, PTSD and wound healing, perhaps involving gene therapy techniques.” When told about her potential to help people, Cameron expressed her excitement over being able to “help other people who are suffering.”

This post was written by Shin Woo Kim and edited by Karolina Zięba.

2 thoughts on “No pain, sane brain: Clues to pain and anxiety treatment

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      You’re welcome 🙂

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