RT Journal Article SR Electronic T1 A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vitro JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 3982 OP 3989 DO 10.1523/JNEUROSCI.15-05-03982.1995 VO 15 IS 5 A1 KH Steen A1 AE Steen A1 PW Reeh YR 1995 UL http://www.jneurosci.org/content/15/5/3982.abstract AB A major role of local acidosis in long lasting excitation and sensitization of cutaneous nociceptors has recently been demonstrated. In inflamed tissue, acid pH meets with a mixture of inflammatory mediators which, by themselves, stimulate nociceptors though being subject to profound tachyphylaxis. We have mimicked this condition in a rat skin-saphenous nerve preparation in vitro which allows direct application of chemicals to the isolated receptive fields at the corium side. Stimulant solutions used were CO2-saturated “synthetic interstitial fluid” (CO2-SIF, pH 6.1), and “inflammatory soup” (IS) in submaximal concentration containing bradykinin, 5-HT, histamine, prostaglandin E2 (all 10(-6) M in SIF at 38.5 degrees C and pH 7.0), and a combination made of CO2-saturated IS (CO2-IS, pH 6.1). Identified mechano-heat sensitive (“polymodal”) C-fiber terminals (n = 36) were treated with these solutions for 5 min at 10 min intervals or for 30 min of sustained stimulation: 20 units responded to CO2-SIF, 12 to IS, whereas 27 units (75%) were excited by CO2-IS. Thus, 6 out of 15 units insensitive to either of the two basic solutions were stimulated by their combination. This enhanced effect of CO2-IS was also expressed in shorter latencies (than with CO2-SIF) and in a significantly larger mean response magnitude of the fiber population: 152 spikes with the combination versus 45 spikes evoked by IS and 93 spikes by CO2-SIF (n = 25; p < 0.002 and < 0.02, respectively, Wilcoxon test).