Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators
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The interaction between cold sensitivity and inflammation in mammals is not entirely understood. We have used adult rat dorsal root ganglion neurones in primary culture together with calcium microfluorimetry to assess the effects of selected inflammatory mediators on cold responses of cold- and menthol-sensitive (most likely TRPM8-expressing) neurones. We observed a high degree of functional co-expression of TRPM8, the receptors for the inflammatory agents bradykinin, prostaglandin E2 and histamine, and TRPA1 in cultured sensory neurones. Treatment with either bradykinin or prostaglandin E2 led to a reduction in the amplitude of the response to cooling and shifted the threshold temperature to colder values, and we provide evidence for a role of protein kinases C and A, respectively, in mediating these effects. In both cases the effects were mainly restricted to the subgroups of cold- and menthol-sensitive cells which had responded to the application of the inflammatory agents at basal temperature. This desensitization of cold-sensitive neurones may enhance inflammatory pain by removing the analgesic effects of gentle cooling.
KeywordsPain TRPM8 TRPA1 Bradykinin Prostaglandin E2
Dorsal root ganglia
Cold- and menthol-sensitive neurones
Protein kinase A
Protein kinase C
8 Bromo cyclic AMP
We are grateful to Prof. Peter Reeh for valuable comments on the manuscript and helpful discussions. We thank Prof. Maria-Luiza Flonta for constant support, Dr. Eva Lörinczi and Dr. Klaus Fendler for logistic help and Cristian Neacşu for technical help. Funding was from the Volkswagen Foundation, the Romanian Research Council (CNCSIS), the Romanian Ministry for Education and Research through its Excellence Grants and the Physiological Society. A.B. acknowledges the Humboldt Foundation for financial support.
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