Abstract
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.
Highlights
Neuropathic pain is a debilitating condition that is poorly understood and often untreatable
We examined the expression of TRPM8 and TRPA1 mRNA in more detail using in situ hybridization of mouse dorsal root ganglia (DRG) sections
In the present study we explored the role of the ion channels TRPM8 and TRPA1 in the development of cold allodynia following nerve injury
Summary
Neuropathic pain is a debilitating condition that is poorly understood and often untreatable. A common complaint of neuropathic pain patients is an increased sensitivity to cold temperatures, or cold allodynia [2,3,4]. This symptom, which is observed in animal models of neuropathic pain [5], leads to pain and discomfort at temperatures that are normally perceived as being innocuously cool. Several candidate thermosensor molecules have been identified belonging to the Transient Receptor Potential (TRP) ion channel family [7] Two of these ion channels, termed TRPM8 and TRPA1, have been proposed to function as cold transducers [8,9]. Many reports have indicated that TRPA1 is not directly gated by cold [16,17,18,19] or may only be weakly activated after prolonged exposure to cold temperatures [20,21,22]
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