Effect of Deep Tissue Incision on pH Responses of Afferent Fibers and Dorsal Root Ganglia Innervating Muscle

Abstract

Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis muscle-nerve preparation and patch clamp recordings from cultured dorsal root ganglia neurons innervating incised and unincised muscle, the authors investigated responses to various pH changes. Incision including the plantar flexor digitorum brevis muscle or sham operation was made in the rat hind paw. On postoperative day 1, in vitro single-fiber recording was undertaken. On the basis of previous studies, the authors recorded from at least 40 fibers per group. Also DiI-labeled dorsal root ganglia innervating muscle from rats undergoing incision and a sham operation were cultured and tested for acid responses, using whole cell patch clamp recordings. The prevalence of responsive group IV afferents to lactic acid pH 6.5 in the incision group (15 of 67; 22.3%) was greater than that in the control group (2 of 35; 5.7%; P=0.022). In dorsal root ganglia neurons innervating muscle, incision increased mean current amplitudes of acid-evoked currents; the acid-sensing ion channel blocker, amiloride 300 μM, inhibited more than 75% of the acid-evoked current, whereas, the transient receptor vanilloid receptor 1 blocker (AMG9810 1 μM) did not cause significant inhibition. The authors' experiments demonstrated that incision increases the responses of flexor digitorum brevis muscle afferent fibers to weak acid solutions, and increased acid-evoked currents in dorsal root ganglia innervating muscle. The authors' data suggest that up-regulation of acid-sensing ion channels might underlie this increased chemosensitivity caused by surgery.