Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators.
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.
Linte
Ramona Madalina
RM
Department of Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, Bucharest, Romania.
Ciobanu
Cristian
C
Reid
Gordon
G
Babes
Alexandru
A
D000698:Analgesia / Q000379:methods; D000818:Animals; D017487:Ankyrins; D000982:Antipruritics / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003080:Cold Temperature; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005727:Ganglia, Spinal / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000494:pharmacology; D008610:Menthol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels / Q000187:drug effects / Q000378:metabolism; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*
D017487:Ankyrins; D000982:Antipruritics; D015220:Calcium Channels; D018836:Inflammation Mediators; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; C480976:Trpa1 protein, rat; C498947:Trpm8 protein, rat; D008610:Menthol; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C