Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1‐expressing nociceptors in the rat

Abstract

Inflammatory hypersensitivity is characterized by behavioural reductions in withdrawal thresholds to noxious stimuli. Although cutaneous primary afferent neurones are known to have lowered thermal thresholds in inflammation, whether their mechanical thresholds are altered remains controversial. The transient receptor potential channel A1 (TRPA1) is a receptor localized to putative nociceptive neurones and is implicated in mechanical and thermal nociception. Herein, we examined changes in the properties of single primary afferents in normal and acutely inflamed rats and determined whether specific nociceptive properties, particularly mechanical thresholds, are altered in the subpopulation of afferents that responded to the TRPA1 agonist cinnamaldehyde (TRPA1-positive afferents). TRPA1-positive afferents in normal animals belonged to the mechanonociceptive populations, many of which also responded to heat or capsaicin but only a few of which responded to cold. In acute inflammation, a greater proportion of afferents responded to cinnamaldehyde and an increased proportion of dorsal root ganglion neurones expressed TRPA1 protein. Functionally, in inflammation, TRPA1-positive afferents showed significantly reduced mechanical thresholds and enhanced activity to agonist stimulation. Inflammation altered thermal thresholds in both TRPA1-positive and TRPA1-negative afferents. Our data show that a subset of afferents is sensitized to mechanical stimulation by inflammation and that these afferents are defined by expression of TRPA1.

The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice

“…Similar to the cinnamaldehyde effect, Inoue et al (1997) reported that the plasma extravasation evoked after reapplication of the TRPA1 receptor agonist, allyl isothiocyanate, on days 1, 3 and 7 was not different from that induced after its initial application. Moreover, Dunham et al (2008) also failed to detect sensitization or desensitization to cinnamaldehyde-induced activation of primary afferent fibers in rats when the stimulus was injected each 5 min. On the other hand, other studies were capable of detecting desensitization to allyl isothiocyanate-induced currents in sensory neurons, neuropeptide release in skin or nociception in rats when the interstimuli interval was from 3 to 20 min (Akopian et al, 2007;Ruparel et al, 2008).…”

The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia

“…The symbols "þ" indicate a response significantly greater than that induced by 0.9% NaCl (t test, p < 0.05). Dunham et al, 2008;Eid et al, 2008;Obata et al, 2005;Petrus et al, 2007) and by in vitro studies showing sustained TRPA1 activation using the perforated patch clamp technique (Koivisto et al, 2012) and intracellular calcium images (Koivisto et al, 2012).…”

Transient Receptor Potential Vanilloid-1 (TRPV1) and Ankyrin-1 (TRPA1) Participate in Visceral Hyperalgesia in Chronic Water Avoidance Stress Rat Model

“…In vitro studies demonstrate that TRPA1 plays as a mechanosensor in DRG and the mechanical thresholds of the TRPA1-positive neurons are lowered with somatic inflammation [20]. Either genetically knocking down TRPA1 or the administration of specific antagonists for TRPA1 could attenuate such mechanical hyperalgesia in certain inflammatory and nerve injury models [16,30,36].…”

“…Therefore the role of TRPA1 in the field of gut sensation arouses recent interest of researchers. It is reported that TRPA1 plays as a mechanosensor [20] and TRPA1 deletion markedly reduced colitis-induced mechanical hyperalgesia in the mice [21]. However, whether TRPV1 and TRPA1 channels are involved in the altered visceral sensation in the chronic psychological stress is not yet evident.…”