Cinnamaldehyde (cinn) is a selective agonist at the Transient Receptor Potential A1 Receptor (TRPA1) that evokes pain in humans (Namer et al. 2005) and nociceptive behaviour in rodents (Bandell et al. 2004). We have determined the effect of cinn on single mechanosensitive primary afferent units in vivo, and on spontaneous activity in dissociated rat dorsal root ganglion (DRG) neurones. Recordings were made from single cutaneous mechanosensitive fibres from teased filaments of the saphenous nerve, in deeply anaesthetised male Wistar rats (250-350g, sodium pentobarbital ~20mg kg-1 h-1 i.v.). Thresholds for activation were determined using receptive field stimulation with graded von Frey hairs, and units were classified as either low or high threshold mechanoreceptors (LTM or HTM) on their baseline responses. Responses to von Frey stimulation were recorded after application of vehicle (DMSO) and cinn (10%) directly to the receptive field. In separate experiments, cinn was administered by close arterial injection (C.A.I.) through a femoral arterial cannula. For in vitro study, DRG were isolated and plated on collagen-coated glass coverslips and incubated in F12 medium until used in experiments. DRG were used on days 3–4 of culture. All data shown are median ± semi-interquartile range. Topical cinn increased the evoked activity in 10 of 19 mechanically sensitive units, representing 9/15 HTMs and 1/4 LTMs. In these units cinn decreased mechanical thresholds compared to vehicle (120 ± 86g DMSO vs. 6 ± 13g cinn, p<0.05, Wilcoxon signed rank test). In the same units, cinn also increased the rate of spontaneous firing (0.03 ± 0.08 Hz veh. vs. 0.12 ± 0.2 Hz cinn, p<0.01, Wilcoxon) and the response evoked by suprathreshold noxious mechanical stimulation (0.1 ± 0.45 Hz veh. vs. 0.6 ± 1.7 Hz cinn, p<0.01, Wilcoxon). C.A.I. cinn (0-80mM) resulted in a dose-related transient increase in action potentials (AP) in the 60 s after cinn administration, in a population of predominately HTMs (0 + 0.9 veh vs. 3.5 ± 6.8 AP cinn, p<0.05 Kruskal Wallis test + Dunns). In 4 cinn responsive units, the cinn-evoked response was unaffected by capsaizepine (20μg/100μl), suggesting that altered activity was not attributable to TRPV1 activation. In isolated DRG neurons, bath application of cinnamaldehyde (250μM) evoked trains of action potentials in a population of small DRG neurons. Our data suggest that activation of TRPA1 receptors both directly activates, and sensitises primary afferent nociceptors to mechanical stimulation. TRPA1 receptors may play a role in mechanonociception and contribute to the development of peripheral hyperalgesia.
University College London 2006 (2006) Proc Physiol Soc 3, C30
Oral Communications: Cinnamaldehyde sensitises and activates rat primary afferent neurons in vivo and in vitro
James Dunham1, Helen Kennedy1, Lucy Donaldson1
1. Department of Physiology, University of Bristol, Bristol, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.