The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.
Cold allodynia is a common feature of neuropathic pain however the underlying mechanisms of this enhanced sensitivity to cold are not known. Recently the transient receptor potential (TRP) channels TRPM8 and TRPA1 have been identified and proposed to be molecular sensors for cold. Here we have investigated the expression of TRPM8 and TRPA1 mRNA in the dorsal root ganglia (DRG) and examined the cold sensitivity of peripheral sensory neurons in the chronic construction injury (CCI) model of neuropathic pain in mice.In behavioral experiments, chronic constriction injury (CCI) of the sciatic nerve induced a hypersensitivity to both cold and the TRPM8 agonist menthol that developed 2 days post injury and remained stable for at least 2 weeks. Using quantitative RT-PCR and in situ hybridization we examined the expression of TRPM8 and TRPA1 in DRG. Both channels displayed significantly reduced expression levels after injury with no change in their distribution pattern in identified neuronal subpopulations. Furthermore, in calcium imaging experiments, we detected no alterations in the number of cold or menthol responsive neurons in the DRG, or in the functional properties of cold transduction following injury. Intriguingly however, responses to the TRPA1 agonist mustard oil were strongly reduced.Our results indicate that injured sensory neurons do not develop abnormal cold sensitivity after chronic constriction injury and that alterations in the expression of TRPM8 and TRPA1 are unlikely to contribute directly to the pathogenesis of cold allodynia in this neuropathic pain model.
Caspani
Ombretta
O
Klinik für Anaesthesiologie und operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Zurborg
Sandra
S
Labuz
Dominika
D
Heppenstall
Paul A
PA
D000818:Animals; D017487:Ankyrins; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000378:metabolism; D008297:Male; D008610:Menthol / Q000737:chemistry; D051379:Mice; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000473:pathology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels / Q000378:metabolism*; D013696:Temperature; D013697:Thermosensing; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
D017487:Ankyrins; D015220:Calcium Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C480976:Trpa1 protein, rat; C498947:Trpm8 protein, rat; D008610:Menthol; D002118:Calcium