Why cooling is beneficial: non-linear temperature-dependency of stimulated iCGRP release from isolated rat skin.

Abstract

The capsaicin receptor in nociceptive neurons is a target for the sensitizing actions of algogenic inflammatory mediators. Capsaicin and potential endogenous ligands are thought not to gate this heat-activated ion channel but to sensitize it so profoundly that even room temperature can open it. We investigated the temperature dependency of capsaicin-induced CGRP release from nociceptive nerve fibers in isolated rat skin over a range of ambient temperatures using different agonist concentrations (10(-7)-10(-5)M) and KCl (60 mM) for control. Ambient temperature (4-40 degrees C) showed no significant influence on the basal iCGRP outflow. The supramaximal capsaicin concentration of 10(-6)M as a stimulus evoked a response that was not significantly diminished by temperatures decreasing from 40 to 24 degrees C but lost 65% of its amplitude between 24 and 14 degrees C (Q(10) approximately 6.7). Such a collapse of the response occurred between 40 and 32 degrees C at lower capsaicin concentration (10(-7)M). The concentration-response curves showed a rightward shift upon cooling from 40 to 24 degrees C and a major loss of slope and maximum effect at 14 degrees C which formally describes a noncompetitive antagonism. KCl-induced iCGRP release showed a much more linear temperature dependency (Q(10) approximately 2.4 between 24 and 14 degrees C). Significant capsaicin responses even at 8 degrees C suggest a contribution of noxious-cold sensitive neurons known to coexpress CGRP and the capsaicin receptor. The heat-activated ion channels (TRPV1-4) are thought to play a significant role in inflammatory pain which is effectively relieved by cooling. The present results contribute to understanding this phenomenon.

• Authors: Tatjana I Kichko, Peter W Reeh
• Journal: Pain (Pain) Vol. 110 Issue 1-2 Pg. 215-9 (Jul 2004) ISSN: 0304-3959 [Print] United States
• PMID: 15275770 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Chloride
• Calcitonin Gene-Related Peptide
• Capsaicin

Topics

• Animals
• Calcitonin Gene-Related Peptide (metabolism)
• Capsaicin (pharmacology)
• Cold Temperature
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay (methods)
• Female
• In Vitro Techniques
• Male
• Potassium Chloride (pharmacology)
• Rats
• Skin (drug effects, metabolism)
• Skin Temperature (drug effects, physiology)
• Statistics, Nonparametric
• Thermosensing (physiology)