title: Activation of sensory neurons contributes to reduce spinal cord injury in rats.
abstract: We previously demonstrated that activation of sensory neurons increases endothelial prostaglandin I(2) (PGI(2)) production by releasing calcitonin gene-related peptide (CGRP). Since PGI(2) reduces post-traumatic spinal cord injury (SCI) by inhibiting tumor necrosis factor (TNF) production, activation of sensory neurons in the spinal cord tissue may ameliorate spinal cord injury. This study examines these possibilities using rat models of compression trauma-induced SCI. Both SB366791, a specific vanilloid receptor antagonist, and CGRP (8-37), a CGRP receptor antagonist, significantly inhibited trauma-induced increases in spinal cord tissue 6-keto-PGF(1alpha) levels. SB366791, CGRP (8-37) and indomethacin (IM) enhanced increases in spinal cord tissue TNF levels at 2h after trauma and exacerbated motor disturbances. Administration of CGRP significantly reduced motor disturbances and inhibited increases in spinal cord tissue TNF levels through enhancement of increases in tissue levels of 6-keto-PGF(1alpha). These observations strongly suggest that activation of sensory neurons might ameliorate compression trauma-induced SCI, inhibiting TNF production through enhancement of endothelial PGI(2) production. Thus, although the spinal cord sensory neurons function as nociceptive neurons, they could also be critically involved in the cytoprotective system that attenuates SCI development and, thus, pharmacological stimulation of spinal cord sensory neurons might contribute to reduce spinal cord injury.
authors.affiliation: Departments of Emergency and Critical Care Medicine, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Kitamura
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
authors.forename: Eiichi
authors.initials: E
authors.lastname: Goto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Masatoku
authors.initials: M
authors.lastname: Arai
authors.forename: Shoichi
authors.initials: S
authors.lastname: Shimada
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D000813:Anilides; D002934:Cinnamates; D016861:Cyclooxygenase Inhibitors; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D010446:Peptide Fragments; D048069:Tumor Necrosis Factors; C058636:calcitonin gene-related peptide (8-37); D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide; D007213:Indomethacin