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Scottish doctors were amazed when a 66-year-old woman underwent a very painful operation at hand for severe arthritis and required little or no pain medication afterwards. Similarly, two years ago, she was diagnosed with severe osteoarthritis of the hip with significant joint degeneration, but she never complained of discomfort before, during or after her hip replacement surgery. .
In fact, the patient told her doctors that she herself burned only once and withdrew her hand from the flame only when she felt the burning flesh. She also scored remarkably low on anxiety and depression tests.
Thinking that the exceptional insensitivity to the woman's pain may have been rooted in her genes, British researchers sequenced and analyzed her genome and discovered an unidentified mutation before, they reported Wednesday to the British Journal of Anesthesia. This mutation, in a region named FAAH-OUT, appears to have the effect of reducing the activity of a neighboring gene called FAAH, known to be involved in the sensation of pain, mood and memory .
FAAH is a protein that breaks down anandamide, also called "bliss molecule", which is a neurotransmitter that binds to cannabinoid receptors. These are some of the same receptors that are activated by marijuana. With less FAAH activity, it was found that this patient had more circulating anandamide levels, which may explain her pain resistance.
Although it is risky to over-treat a patient's case, the researchers said their discovery could have interesting implications for the treatment of acute and chronic pain. Previous genetic targets for the treatment of pain focused on sodium ion channels and the transmission of pain signals from the peripheral nervous system to the brain. FAAH and FAAH-OUT change the way pain signals are interpreted by the brain.
Although studies and trials of experimental drugs against FAAH have failed, the researchers said FAAH-OUT may offer a new way to target the endocannabinoid receptor. At a time when approximately 130 Americans are dying every day as a result of an opioid overdose, scientists and drug companies are actively seeking alternative non-opioid drugs for the treatment of acute and chronic pain.
"This discovery opens up many possibilities for drug development using the endocannabinoid pathway to alter the effects of pain," said Dr. Dev Srivastava, one of the investigators and consultant in anesthesia and in treatment of pain at Raigmore Hospital in Inverness, Scotland. "This could be developed into a miracle drug to treat patients in surgery or those suffering from cancer or chronic pain."
However, as in the Scottish patient, the complete elimination of the sensation of pain can be problematic. Similar to patients suffering from painful diabetic neuropathies, the decrease in extreme sensation at the extremities can sometimes result in repeated injuries that the patient does not notice. Dr. James Cox, another author and keynote speaker at the Wolfson Institute for Biomedical Research at University College London, said, "Pain is a vital warning system to protect you from the events damaging and putting your life in danger. "
Another disadvantage of endocannabinoids and their receptors is that poor memory and learning can be undesirable byproducts. Researchers have reported that the Scottish woman has reported memory loss, which is what we see in mice carrying the FAAH gene.
The researchers also quickly warned patients and providers that while this research demonstrates analgesic effects in the endocannabinoid pathway, this does not mean that recreational cannabis works the same way or can be used as a substitute for control. pain. In the United States, the opioid crisis began with increased reliance on legal analgesics, followed by spikes in the use of heroin and illicitly manufactured fentanyl. If drugs using the endocannabinoid pathway become predominant, illegal counterparts could also become a concern.
Republished with permission of STAT. This article was published on March 27, 2019
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