What has chili to do with pain treatment?
Chili peppers contain capsaicin, which is responsible for the hot and burning sensation when ingesting chili pepper. Why is this important for pain?
One of the fundamental discoveries in the field of pain is the identification of the cellular target of capsaicin, called TRPV1. TRPV1 is responsible not only for the hot sensation caused by chili peppers, but also for the transduction of noxious stimuli (such as heat) into a painful signal. This discovery led to the award of the Nobel Prize in Physiology in 2021 to David Julius.
It has been observed that some patients with neuropathic pain benefit from the application of different forms of capsaicin to the skin. This may seem illogical, as capsaicin causes pain, but I will try to explain why it can also produce pain relief.
How does capsaicin relieve pain?
Creams containing low concentrations of capsaicin are available over the counter, and have to be applied multiple times per day. A patch containing a high concentration of capsaicin is FDA-approved for certain forms of neuropathic pain, and is applied every few months.
A first application of capsaicin to the skin frequently causes burning pain, but subsequent exposures to capsaicin cause less and less pain. This is called "desensitization", meaning that the skin becomes less and less sensitive to pain. Why does it happen?
It has been shown that capsaicin causes a degeneration or dysfunction of the nerve endings that transmit the pain. This way, the nerves become less able to transmit the pain signal. Pain relief is temporary, typically few months, but capsaicin can be applied again when pain recurs.
It is commonly believed that recurrence of pain is due to regeneration of the nerves. Once the nerves regrow, they would again be able to transmit painful signals to the spinal cord and the brain. However, it has been shown that pain relief persists even after the nerves regain their ability to transmit the pain. This challenges the belief that pain relief caused by capsaicin is related primarily to nerve degeneration or dysfunction.
A new study suggests that capsaicin may support regrowth of nerves to their healthy pre-disease state
In neuropathic pain, nerves display profound alterations in their structure and function that cause aberrant discharge of pain signals. A new study postulates that capsaicin first causes degeneration of these aberrant nerves, but then a regeneration may take place that leads to restoration of their pre-disease "healthy" condition. This could explain longer-lasting pain relief.
Why is this potentially relevant?
In my commentary in the journal "Pain", I discuss the potential implications of these findings for future research and the perspective to optimize clinical regimens to improve the effectiveness of capsaicin. Here I summarize my thoughts.
If we were able to optimize the regeneration process of the damaged nerves to their pre-disease "healthy" condition, capsaicin treatment could lead to long-lasting or even permanent pain relief, at least in some patients. To potentially achieve that, we could revise the currently recommended clinical regimen, which consists in the application of capsaicin patch every few months. One option that could be examined in future trials is to perform a series of 2-3 treatments of high concentrated capsaicin with few days interval, instead of the currently recommended single applications. This might lead to a a more extensive initial degeneration of nerves, and hopefully to their subsequent regrowth to normal function.
Genetic studies on nerves ("transcriptomics") are now feasible. These studies may reveal molecular mechanisms of regeneration. Examining nerve transcriptomics over time could allow the discovery of new molecular targets of therapeutics that support nerve regeneration. Such treatments would pursue the goal of promoting healing, rather that merely treating the pain.