In conditions such as arthritis or infection, the tissue involved at these sites becomes acidic. While normal human tissue has a neutral pH of approximately 6.5 - 7.5 (similar to water), tissue acidosis can cause a drop in cellular pH below 6.0 closer to that of household vinegar. When the cellular environment becomes acidic, both VR1 and a second nociceptor - acid sensing ion channels (ASICs) - are activated. In previous experiments in mice, scientists have found that the activation of VR1 requires extremely severe acidification - pH less than 6.0. This suggests that another pain sensor plays a role in nociception, specifically at pH levels greater than 6.0. Despite experimental data revealing that mouse neurons lacking ASICs are severely deficient in their responses to acidic stimuli, controversy remains about the function of ASICs in mammals.
In a study reported in the October 21 issue of the Journal of Clinical Investigation (JCI) by Shinya Ugawa and colleagues from the Nagoya City University Medical School, Japan, the authors demonstrated that both VR1 and ASICs are involved in the sensing of acid-evoked pain in humans and that each type of nociceptor mediates this pain perception at very specific pH ranges. The authors infused solutions of varying pH levels under the skin of the underside of the upper forearm of healthy male volunteers who were subsequently asked to estimate the intensity of the induced pain on a 0-10 scale. To determine which particular
Contact: Brooke Grindlinger, PhD
Journal of Clinical Investigation