title: The effects of intraspinal L-NOARG or SIN-1 on the control by descending pathways of incisional pain in rats.
abstract: The modulation by spinal nitric oxide (NO) of descending pathways travelling through the dorsal lateral funiculus (DLF) is a mechanism proposed for the antinociceptive effects of drugs that changes the NO metabolism. In this study we confirm that a surgical incision in the mid-plantar hind paw of rats reduces the threshold to mechanical stimulation with von Frey filaments. The incisional pain was further increased in rats with ipsilateral DLF lesion. Intrathecal L-NOARG (50-300 microg), or SIN-1 (0.1-5.0 microg) reduced, while SIN-1 (10 and 20 microg) intensified the incisional pain in rats with sham or effective lesion of the DLF. Stimulation of the dorsal raphe (DRN) or anterior pretectal (APtN) nuclei with stepwise increased electrical currents (7, 14, 21, 28 and 35 microA r.m.s.) produced a current-related reduction of the incisional pain. These nuclei activate pain inhibitory pathways that descend to the spinal cord mainly through the DLF. Intrathecal SIN-1 (5 microg) reduced, SIN-1 (20 microg) decreased and L-NOARG (150 microg) did not change the EC50 for the DRN or APtN stimulation-induced reduction of incisional pain. We conclude that the antinociceptive effects of L-NOARG or low doses of SIN-1 are independent on the activity of descending pain control pathways travelling via the DLF, but the antinociceptive effect of stimulating electrically the DRN or APtN can be summated to the effect of low dose of SIN-1 or overcome by the high dose of SIN-1.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirão Preto-USP, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Vania Aparecida V
authors.initials: VA
authors.lastname: Kina
authors.forename: Cristiane F
authors.initials: CF
authors.lastname: Villarreal
authors.forename: Wiliam A
authors.initials: WA
authors.lastname: Prado
mesh_terms: D000698:Analgesia; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects* / Q000503:physiopathology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006614:Hindlimb; D007278:Injections, Spinal; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000503:physiopathology; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy / Q000517:prevention & control; D017288:Pain Threshold / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D019335:Nitroarginine; C002385:linsidomine; D008981:Molsidomine