title: Involvement of the glutamatergic system in the nociception induced intrathecally for a TRPA1 agonist in rats.
abstract: The transient receptor potential ankyrin 1 (TRPA1) is expressed in peripheral and spinal terminals of sensory neurons, jointly to the vanilloid receptor (TRPV1). A relevant peripheral role of TRPA1 receptor has been implicated in a variety of processes, including the detection of noxious cold, and diverse painful stimulus, but the functional role of TRPA1 receptor in nociceptive transmission at spinal cord in vivo is poorly known. Therefore, the aim of this study was to evaluate whether the glutamatergic system is involved in the transmission of nociceptive stimulus induced for a TRPA1 agonist in the rat spinal cord. We observed that cinnamaldehyde, a TRPA1 agonist, on spinal cord synaptosomes leads to an increase in [Ca(2+)](i) and a rapid release of glutamate, but was not able to change the specific [(3)H]-glutamate binding. In addition, spinally administered cinnamaldehyde produced heat hyperalgesia and mechanical allodynia in rats. This behavior was reduced by the co-injection (i.t.) of camphor (TRPA1 antagonist) or MK-801 (N-methyl-D-aspartate (NMDA) receptor antagonist) to cinnamaldehyde. Besides, the pretreatment with resiniferatoxin (RTX), a potent TRPV1 agonist, abolished the cinnamaldehyde-induced heat hyperalgesia. Here, we showed that intrathecal RTX results in a decrease in TRPA1 and TRPV1 immunoreactivity in dorsal root ganglion. Collectively, our results demonstrate the pertinent participation of spinal TRPA1 in the possible enhancement of glutamatergic transmission of nociceptive signals leading to increase of the hypersensitivity, here observed as heat hyperalgesia. Then the modulation of spinal TRPA1 might be a valuable target in painful conditions associated with central pain hypersensitivity.
authors: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. jonzeni@hotmail.com
authors: J Z
authors: JZ
authors: Klafke
authors: M A
authors: MA
authors: da Silva
authors: G
authors: G
authors: Trevisan
authors: M F
authors: MF
authors: Rossato
authors: C R
authors: CR
authors: da Silva
authors: G P
authors: GP
authors: Guerra
authors: J G
authors: JG
authors: Villarinho
authors: F K
authors: FK
authors: Rigo
authors: G D
authors: GD
authors: Dalmolin
authors: M V
authors: MV
authors: Gomez
authors: M A
authors: MA
authors: Rubin
authors: J
authors: J
authors: Ferreira
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D006358:Hot Temperature; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism; D059225:Nociception / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000819:agonists*; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; D050916:TRPV Cation Channels; C480976:Trpa1 protein, rat; C493922:Trpv1 protein, rat; D018698:Glutamic Acid; D016202:N-Methylaspartate; D000171:Acrolein; C012843:cinnamaldehyde; D002118:Calcium