The ability to feel pain is an extremely important adaptation, without which we would have no way of knowing when external stimuli are harming us. For this reason, people born with analgesia – a condition which prevents them from feeling pain – face considerable dangers in their daily lives, since they are prone to unwittingly placing themselves in physical danger. However, a team of researchers at University College London may have now found a potential solution to the problem, by administering a drug normally used to reverse opiate overdoses to enable a 39-year-old woman to experience pain for the very first time, according to a paper published in the journal Nature.
Analgesia is caused by a mutation to a gene called SCN9A, which encodes channels – specifically Nav1.7 channels – that facilitate the transport of sodium across sensory nerves, enabling the transmission of pain signals to the brain. Without these channels, these signals cannot be relayed, and pain cannot be felt. Interestingly, since Nav1.7 channels are also found in olfactory neurons, their absence can sometimes result in an inability to smell – a condition known as anosmia.
By genetically engineering mice to inhibit the expression of SCN9A, the researchers noted that not only did they manage to prevent the formation of Nav1.7 channels, but they also stimulated an increase in endogenous opioid peptides. These are short sequences of amino acids which are produced naturally within the body and bind to the opioid receptors in the brain in order to dull feelings of pain – much like opioid drugs such as heroin. Consequently, they hypothesized that chronic insensitivity to pain may be partially caused by an increase in opioid peptides, and partially by an absence of Nav1.7 channels.
They therefore decided to administer a drug called naloxone, which binds to the opioid receptors in the brain in order to block them, thereby preventing the opioid peptides from producing a pain-killing effect. Because of this mechanism of action, naloxone is traditionally used as a means of reversing the effects of opiate drug overdoses.
After naloxone had been administered, the researchers tested the pain responses of the mice by applying both heat and pressure to their paws in order to see if this would make them withdraw their limbs. What they found was “a dramatic reversal of analgesia and restoration of thermal and mechanical pain thresholds” in these mice thanks to the use of naloxone.
Taking the experiment a step further, they recruited a human sufferer of analgesia to take part in a repetition of the experiment. After verifying that the participant was “completely unaware” of heat being applied to their skin under normal conditions, they then administered naloxone, following which the woman was able to detect the stimulus 80 percent of the time.
Since the effects of naloxone wear off after about an hour, this is not a permanent solution to analgesia, although it does reveal new information about how the condition may be treated. According to New Scientist, study co-author John Wood claims the research could also help scientists develop better pain-relieving therapies for sufferers of painful conditions such as arthritis, while adding that the woman who took part in the experiment “quite enjoyed” the experience.