Effects of TRPA1 Agonists Mustard Oil and Cinnamaldehyde on Lumbar Spinal Wide-Dynamic Range Neuronal Responses to Innocuous and Noxious Cutaneous Stimuli in Rats

Abstract

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...

Activation of Lumbar Spinal Wide-Dynamic Range Neurons by a Sanshool Derivative

“…Consistent with prior observations (Carstens 1997;Merrill et al 2008), the majority of the present WDR neurons responded to thermal stimuli and the irritant chemicals AITC and capsaicin, in addition to IBA. No IBA-responsive neurons were found that did not additionally respond to AITC and/or capsaicin, which induce burning pain, suggesting that "tingle-specific" neurons are rare or nonexistent.…”

“…The spinous processes of L1 and T13 were removed and the transverse processes of L2 and T12 were clamped for stability (for details, see Merrill et al 2008). After exposure of the spinal cord Address for reprint requests and other correspondence: E. Carstens,…”

“…The spinal cord was postfixed in 10% buffered formalin and subsequently cut on a freezing microtome as described previously (Merrill et al 2008). Spinal cord sections were examined under the light microscope to identify lesion sites.…”

Physiological, pharmacological, and behavioral evidence for a TRPA1 channel that can elicit defensive responses in the medicinal leech

“…Alternatively, these findings could be evidence of an interaction between TRPA1 and TRPV channels. AITC can cause sensitization of responses to heat (Martin et al, 2004;Simons et al, 2004;Carstens and Mitsuyo, 2005;Merrill et al, 2008;Sawyer et al, 2009) and this is thought to be the result of TRPA1-mediated sensitization of TRPV1 (Jansen et al, 1978). Because HC030031 may operate as an allosteric modulator (Xiao et al, 2008), it is possible that this antagonist elicits a conformational change in TRPA1 that, while antagonizing channel function, is able to activate the biochemical pathways responsible for TRPV sensitization.…”

How irritating: the role of TRPA1 in sensing cigarette smoke and aerogenic oxidants in the airways

“…7,8). Specifically, TRPA1 is exclusively activated by mustard oil, cinnamaldehyde (a compound found in cinnamon), lipids (9), chlorine (see below), the pollutant acrolein (10)(11)(12)(13)(14), as well as endogenous aldehydes (15). TRPA1 is not inhibited by capsazepine but rather by a specific antagonist, HC-030031 (6).…”