Spinal mechanisms of antinociceptive action caused by guanosine in mice.
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.
Schmidt
André P
AP
Graduate Program in Biochemistry, Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. aschmidt@ufrgs.br
Böhmer
Ana Elisa
AE
Schallenberger
Cristhine
C
Antunes
Catiele
C
Pereira
Mery Stéfani L
MS
Leke
Renata
R
Wofchuk
Susana T
ST
Elisabetsky
Elaine
E
Souza
Diogo O
DO
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
D000700:Analgesics; D011687:Purines; D006151:Guanosine; D018698:Glutamic Acid; C030985:purine