Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, PC114

Poster Communications

Direct modulatory effect of inflammatory mediators on cold- and menthol-sensitive neurons from rat dorsal root ganglia

C. Doran1, G. Reid1

1. Physiology, University College Cork, Cork, Ireland.


It has recently been shown that inflammatory mediators (bradykinin and prostaglandin E2) inhibit responses to cooling in cold-and menthol-sensitive neurons from dorsal root ganglia (DRGs), which probably express the cold and menthol receptor TRPM8. This inhibition may be involved in inflammatory pain conditions (1). However, the high concentration of inflammatory mediators (10 μM) used in that study increased [Ca2+]i immediately on application, leading us to question whether the inhibition of TRPM8 was due to a direct effect of inflammatory mediators or simply to desensitization following activation of the neurons. We have now examined the effects of an inflammatory soup of bradykinin, prostaglandin E2 and serotonin (each at 1 μM) on cold responsiveness of rat DRG neurons. DRG neurons from adult Sprague Dawley rats were cultured with 100 ng/ml nerve growth factor for 12-24 hours and responsiveness of individual neurons was evaluated using calcium microfluorimetry (ΔF/F0). As previously described (1), neurons were classified as cold- and menthol-sensitive (CSMS) or cold-sensitive and menthol-insensitive (CSMI). Of 647 neurons, 151 (23.3 %) were cold sensitive, and of these 38 neurons (29 %) were also sensitive to menthol (CSMS neurons). Of these 38 CSMS neurons, 14 (37 %) showed a decrease in the amplitude of the response to cooling (ΔF/F0 decreased from 0.23 +/- 0.04 to 0.10 +/- 0.04, mean ± SD, n= 14; P=0.0008, Student’s paired t test). Of the remaining 113 cold-sensitive neurons which did not respond to menthol (CSMI neurons), 28 (25 %) showed a decrease in the amplitude of the response to cooling (ΔF/F0 decreased from 0.29 +/-0.04 to 0.14 +/-0.03, n=28, P<0.0001, Student’s paired t test). The lower concentrations of inflammatory mediators used here avoided direct activation of neurons at base temperature of 32°C. Dampening of the response to cooling at these low concentrations is thus indicative of a direct modulatory effect of inflammatory mediators on cold sensitive neurons, rather than simply a desensitization following activation.

Where applicable, experiments conform with Society ethical requirements