Transient receptor potential ion channels

Transient receptor potential (TRP) ion channels are sensory transducers, many of which are expressed in noci-ceptive primary sensory neurons where they are involved in generating chemical- and thermal-evoked pain sensa-tions.82 In particular, TRPV1 responds to noxious heat (temperatures >43°C) and the pungent ingredient in hot chilli peppers, capsaicin, producing the classic burning sensation. In contrast, TRPA1 responds to cold temperatures (<18°C) and to the irritant, mustard oil, also producing a burning sensation.

Following nerve injury, the phenotype of cells expressing TRP channels fundamentally changes so that TRPV1

and TRPA1 are also expressed by neurons of a non-nociceptive phenotype. Expression of TRPV1 has been shown to decrease in injured nociceptive neurons, while they increase in the neighboring uninjured neurons.83 This includes novel expression in large diameter, low threshold A-fibers which may indicate a phenotypic switch contributing to symptoms of neuropathic pain. Similarly, TRPA1 expression is increased in a subset of small diameter primary sensory neurons following nerve injury likely inducing cold hypersensitivity.84 Interfering with TRPA1 channel function using antisense knockdown technology abolishes hypersensitivity to a cold stimulus following spinal nerve ligation in the rat.85 Therefore, targeting specific TRP channels may prove useful as analgesic strategies in the future.

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