Proceedings of The Physiological Society

University College Dublin (2009) Proc Physiol Soc 15, C43

Oral Communications

Activation of the capsaicin receptor TRPV1 desensitises the nociceptive ion channel TRPA1 in rat dorsal root ganglion neurones

C. Doran1, G. Reid1

1. Physiology, University College Cork, Cork, Ireland.


Transient Receptor Potential A1 (TRPA1) is an ion-channel receptor implicated in a number of nociceptive pathways including cold-induced pain and the detection of noxious stimuli such as isothiocyanates. It is specifically activated by cinnamaldehyde and mustard oil. TRPA1 is often co-expressed with the heat/capsaicin receptor TRPV1 in primary sensory neurones. To clarify how TRPV1 activation affects the activity of TRPA1, we have examined the effects of capsaicin on the cinnamaldehyde sensitivity of dorsal root ganglion (DRG) neurones. Adult Sprague-Dawley rats were killed by 100 % CO2 inhalation followed by decapitation, and dissociated DRG neurones were cultured with nerve growth factor for 12-24 hours. Capsaicin (1 μM) and cinnamaldehyde (200 μM) responsiveness of individual neurones was evaluated using Calcium Green-1 microfluorimetry (ΔF/F0). TRPA1 activation in DRG neurones was significantly reduced as evidenced by a diminished sensitivity to cinnamaldehyde (ΔF/F0: 0.03 ± 0.003, mean ± SEM, n=299, vs. control 0.3 ± 0.02, n=367; P<0.0001, Student’s unpaired t test). Next, we determined whether the observed capsaicin-mediated inhibition was dependent upon TRPV1 activation. DRG neurones were pre-incubated with 10mM capsazepine, a TRPV1 antagonist, before evaluating capsaicin-induced inhibition of TRPA1. Capsazepine reduced the response of TRPV1 to capsaicin (ΔF/F0 decreased from 0.45 ± 0.03, n=299, to 0.14 ± 0.02, n=156; P<0.001), and reduced the capsaicin-induced inhibition of TRPA1 (response to cinnamaldehyde increased from ΔF/F0 = 0.03 ± 0.003, n=299, to 0.16 ± 0.03, n=156; P<0.0001). In order to determine whether the capsaicin-induced desensitisation of TRPA1 occurs via a calcium-dependent mechanism, we depolarised DRG neurones using 50 mM KCl. This concentration elicits an increase in [Ca2+]i similar to that induced by 1 μM capsaicin in TRPV1-expressing neurones, and desensitised TRPA1 to a similar degree: the response to cinnamaldehyde (ΔF/F0 = 0.02 ± 0.002, n=35) was comparable to that following capsaicin-mediated inhibition. We conclude that the desensitising effect of capsaicin on TRPA1 is dependent on a TRPV1-mediated increase in [Ca2+]i. This mechanism could be a potential pharmacological target for modulating TRPA1-mediated nociceptive pathways.

Where applicable, experiments conform with Society ethical requirements