title: Activation of p38 MAPK through transient receptor potential A1 in a rat model of gastric distension-induced visceral pain.
abstract: Afferent fibers innervating the gastrointestinal tract have major roles in consciously evoked sensations including pain. We reported previously that the activation of ERK1/2, a member of the mitogen-activated protein kinase (MAPK) family, in primary sensory neurons was involved in acute visceral pain. Moreover, we also revealed that this activation of ERK1/2 occurred through transient receptor potential (TRP) A1, a member of the TRP family of ion channels. In contrast, it is known that the activation of p38 MAPK (p38) contributes to the development and maintenance of inflammatory and neuropathic pain. On the basis of these results, the aim of this study was to investigate the involvement of p38 and TRPA1 in acute visceral pain. Male Sprague-Dawley rats were used. Electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. We then examined the phosphorylated-p38 (p-p38) labeling in the dorsal root ganglion (DRG) after GD using immunohistochemistry. Noxious GD induced p-p38 in DRG neurons with a peak at 2 min after GD. We also found a stimulus intensity-dependent increase in the number of p-p38-immunoreactive neurons in the DRG. Intrathecal administration of the p38 inhibitor, SB203580, attenuated the electromyographic response to noxious GD. Furthermore, intrathecal administration of TRPA1 antisense oligodeoxynucleotide decreased the p38 activation in DRG neurons. The activation of p38 pathways in DRG neurons by noxious GD may be correlated with the activation state of the primary afferent neurons through TRPA1, and further, involved in the development of visceral pain.
authors.affiliation: Department of Anatomy and Neuroscience, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miwa
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism*; D059265:Visceral Pain / Q000201:enzymology* / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D011725:Pyridines; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580