Intraplantar injection of hyaluronic acid at low pH into the rat hindpaw produces tissue acidosis and enhances withdrawal responses to mechanical stimuli.

Application of buffers covering a range of acidic pH values activates and sensitizes nociceptors and produces pain. The purpose of this study was to determine whether a range of acidic pH in tissue produces mechanical hyperalgesia. Tissue acidosis was produced in the hindpaw of the rat by intraplantar injections of hyaluronic acid (HA) adjusted to pH 7.4, 6.0, 5.0, 4.0 or 3.0. Mechanical hyperalgesia was assessed by evaluating responses to application of a von Frey monofilament to the plantar surface before and after injection of HA. In separate experiments, magnitude of tissue acidosis produced by injection of HA was determined by measuring pH of intraplantar tissue using a pH microelectrode. Although needle stick alone produced mechanical hyperalgesia, intraplantar injections of HA at pH 6.0 or 5.0 produced significantly greater mechanical hyperalgesia. In contrast, mechanical hyperalgesia produced by injection of HA at pH 7.4, 4.0 or 3.0 was not different from that produced by needle stick. Although injection of HA at low pH produced tissue acidosis in a pH dependent manner, only a narrow range of tissue acidosis (pH = 6.38-6.00) produced mechanical hyperalgesia. Our data suggest that tissue acidosis induces mechanical hyperalgesia; however, the range of tissue pH that produces this effect is limited.