@article {Steen3982, author = {KH Steen and AE Steen and PW Reeh}, title = {A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vitro}, volume = {15}, number = {5}, pages = {3982--3989}, year = {1995}, doi = {10.1523/JNEUROSCI.15-05-03982.1995}, publisher = {Society for Neuroscience}, abstract = {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 {\textquotedblleft}synthetic interstitial fluid{\textquotedblright} (CO2-SIF, pH 6.1), and {\textquotedblleft}inflammatory soup{\textquotedblright} (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 ({\textquotedblleft}polymodal{\textquotedblright}) 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).}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/15/5/3982}, eprint = {https://www.jneurosci.org/content/15/5/3982.full.pdf}, journal = {Journal of Neuroscience} }