A dominant role of acid pH in inflammatory excitation and sensitization of nociceptors in rat skin, in vitro.
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).(ABSTRACT TRUNCATED AT 250 WORDS)
Steen
K H
KH
Institut für Physiologie I, Universität Erlangen-Nürnberg, Germany.
Steen
A E
AE
Reeh
P W
PW
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D012867:Skin / Q000294:innervation*
D012701:Serotonin; D006632:Histamine; D015232:Dinoprostone; D001920:Bradykinin