Effects of TRPA1 agonists mustard oil and cinnamaldehyde on lumbar spinal wide-dynamic range neuronal responses to innocuous and noxious cutaneous stimuli in rats. J Neurophysiol 99: 415-425, 2008. First published October 17, 2007 doi:10.1152/jn.00883.2007. Mustard oil [allyl isothiocyanate (AITC)] and cinnamaldehyde (CA), agonists of the ion channel TRPA1 expressed in sensory neurons, elicit a burning sensation and heat hyperalgesia. We tested whether these phenomena are reflected in the responses of lumbar spinal wide-dynamic range (WDR) neurons recorded in pentobarbital-anesthetized rats. Responses to electrical and graded mechanical and noxious thermal stimulation were tested before and after cutaneous application of AITC or CA. Repetitive application of AITC initially increased the firing rate of 52% of units followed by rapid desensitization that persisted when AITC was reapplied 30 min later. Responses to noxious thermal, but not mechanical, stimuli were significantly enhanced irrespective of whether the neuron was directly activated by AITC. Windup elicited by percutaneous or sciatic nerve electrical stimulation was significantly reduced post-AITC. These results indicate that AITC produced central inhibition and peripheral sensitization of heat nociceptors. CA did not directly excite WDR neurons, and significantly enhanced responses to noxious heat while not affecting windup or responses to skin cooling or mechanical stimulation, indicating a peripheral sensitization of heat nociceptors. I N T R O D U C T I O NMustard oil [allyl isothiocyanate (AITC)] and cinnamic aldehyde (CA) are agonists of the transient receptor potential (TRP) channel TRPA1 (Bandell et al. 2004;Bautista et al. 2006;Jordt et al. 2004). When applied to skin, they elicit burning pain, thermal hyperalgesia, and mechanical allodynia (Koltzenburg et al. 1992;Namer et al. 2005). In the oral or nasal mucosa, AITC and CA elicit burning irritation that decreases (desensitizes) across trials of repeated application (Brand and Jacquot 2002;Prescott and Swain-Campbell 2000;Simons et al. 2003), as well as heat hyperalgesia (Albin et al. 2007). Lingual application of AITC or CA excites neurons in the trigeminal subnucleus caudalis (Vc) Simons et al. 2004;Zanotto et al. 2007). AITC excitation of Vc neurons exhibits a desensitizing temporal pattern while sensitizing responses to noxious heat (Simons et al. 2004). We presently tested whether spinal wide-dynamic range (WDR)-type dorsal horn neuronal responses to repeated cutaneous application of AITC or CA similarly exhibit a desensitizing pattern and whether their responses to mechanical and noxious thermal stimuli are enhanced after application of these chemicals, consistent with human psychophysical observations. We presently focused on WDR neurons for two reasons. First, WDR neurons respond to innocuous mechanical as well as noxious thermal stimuli, allowing assessment of the effects of AITC and CA on both types of responses within the same neuronal population, which would not be possible with no...