Abstract
Recently, the molecular substitutes of thermoreceptors of the primary afferents have been clarified. These include six members of the transient receptor potential (TRP) family of nonselective cation channels; TRPV1 (renamed from VR1), TRPV2 (renamed from VRL1), TRPV3, TRPV4, TRPM8 (also known as CMR1), and TRPA1 (renamed from ANKTM1). Several mechanisms have been implicated in underlying the perception of cold, most notably the activation of TRPA1 and TRPM8. Between the two channels, TRPA1 is more likely to be involved in nociception because the temperature threshold for its activation is about 17°C, close to the reported threshold for cold nociceptors. We investigated the expression of TRPA1 and TRPM8 in dorsal root ganglion (DRG) neurons following peripheral inflammation induced by complete Freund's adjuvant (CFA). TRPA1 mRNA expression increased in the small- and medium-sized DRG neurons at 1 and 3 days after peripheral inflammation and the levels were back to normal by 7 days. This up-regulation corresponded well with the development and maintenance of inflammation-induced cold hyperalgesia of the hind paw. In contrast, there was no change in expression of TRPM8 mRNA, or in the percentage of TRPM8-immunoreactive neurons observed over 7 days after the CFA injection. Our data suggests that increased TRPA1 in primary afferent neurons may contribute to the exaggerated cold response observed in this peripheral inflammation model. Silencing of the TRPA1 gene in nociceptors may be potential targets for the development of novel analgesics. [Jpn J Physiol 55 Suppl:S11 (2005)]
