title: Spinal mechanisms of antinociceptive action caused by guanosine in mice.
abstract: It is well known that adenine-based purines exert multiple effects on pain transmission. Recently, we have demonstrated that intracerebroventricular (i.c.v.) administered guanine-based purines are antinociceptive against chemical and thermal pain models in mice. The present study was designed to further investigate the antinociceptive effects of guanosine in mice. Animals received an intrathecal (i.t.) injection of vehicle (0.1 mN NaOH) or guanosine (10 to 400 nmol). Measurements of cerebrospinal fluid (CSF) purine levels and spinal cord glutamate uptake were performed. Guanosine produced dose-dependent antinociceptive effects against tail-flick, hot-plate, intraplantar (i.pl.) capsaicin, and i.pl. glutamate tests. Additionally, i.t. guanosine produced significant inhibition of the biting behavior induced by i.t. injection of glutamate (175 nmol/site), AMPA (135 pmol/site), kainate (110 pmol/site), trans-ACPD (50 nmol/site), and substance P (135 ng/site), with mean ID(50) values of 140 (103-190), 136 (100-185), 162 (133-196), 266 (153-461) and 28 (3-292) nmol, respectively. However, guanosine failed to affect the nociception induced by NMDA (450 pmol/site) and capsaicin (30 ng/site). Intrathecal administration of guanosine (200 nmol) induced an approximately 120-fold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by i.pl. capsaicin. This study provides new evidence on the mechanism of action of guanosine presenting antinociceptive effects at spinal sites. This effect seems to be at least partially associated with modulation of glutamatergic pathways by guanosine.
authors.affiliation: Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. aschmidt@ufrgs.br
authors.forename: André P
authors.initials: AP
authors.lastname: Schmidt
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Böhmer
authors.forename: Cristhine
authors.initials: C
authors.lastname: Schallenberger
authors.forename: Catiele
authors.initials: C
authors.lastname: Antunes
authors.forename: Mery Stéfani L
authors.initials: MS
authors.lastname: Pereira
authors.forename: Renata
authors.initials: R
authors.lastname: Leke
authors.forename: Susana T
authors.initials: ST
authors.lastname: Wofchuk
authors.forename: Elaine
authors.initials: E
authors.lastname: Elisabetsky
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006151:Guanosine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009448:Neurochemistry; D010146:Pain / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism; D011687:Purines / Q000134:cerebrospinal fluid; D013131:Spine / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D011687:Purines; D006151:Guanosine; D018698:Glutamic Acid; C030985:purine