Aims: 

TRPA1 and TRPM8 belong to the TRP ion channel family and are candidates for cold sensing. The aim of our study was to investigate the effects of bradykinin (BK) and prostaglandin E2 (PGE2) on TRPA1 and TRPM8 in mammalian dorsal root ganglion (DRG) neurons.

Methods: 

The change in intracellular [Ca²⁺] was monitored in cultured rat DRG neurons using calcium microfluorimetry.

Results: 

Sensitivity to TRPM8 (cold, 18 C and menthol, 100 mM) and TRPA1 (cinnamaldehyde, CA, 100 mM) agonists was strongly coexpressed with sensitivity to inflammatory mediators BK (10 mM) and PGE2 (10 mM). Both BK and PGE2 inhibited the response to cooling in cold and menthol sensitive (CMS) DRG neurons, which are likely to express TRPM8. The effect of BK and PGE2 on CMS neurons was mediated by PKC and PKA, respectively. In control experiments, cultured DRG neurons were submitted to two consecutive applications of CA (100 mM for 3 min, at 10 min interval), while in a separate group of neurons, the second application of CA was preceded by a 1 min application of PGE2 (1 mM). CA-responsive neurons were divided into PGE2-sensitive and PGE2-insensitive. In the latter subgroup, PGE2 sensitised the response to CA by about 68% (p = 0.02 compared to control conditions).

Conclusions: 

Our results indicate that while reducing the analgesic effect of cooling by desensitizing cold receptors, inflammatory mediators have a sensitizing action on native TRPA1. Both these effects are likely to be involved in inflammatory hyperalgesia.