Mechanisms involved in the antinociception induced by systemic administration of guanosine in mice.
OBJECTIVE
It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) administration of guanosine on mice pain models. Additionally, investigation into the mechanisms of action of guanosine, its potential toxicity and cerebrospinal fluid (CSF) purine levels were also assessed.


METHODS
Mice received an i.p. or p.o. administration of vehicle (0.1 mM NaOH) or guanosine (up to 240 mg x kg(-1)) and were evaluated in several pain models.


RESULTS
Guanosine produced dose-dependent antinociceptive effects in the hot-plate, glutamate, capsaicin, formalin and acetic acid models, but it was ineffective in the tail-flick test. Additionally, guanosine produced a significant inhibition of biting behaviour induced by i.t. injection of glutamate, AMPA, kainate and trans-ACPD, but not against NMDA, substance P or capsaicin. The antinociceptive effects of guanosine were prevented by selective and non-selective adenosine receptor antagonists. Systemic administration of guanosine (120 mg x kg(-1)) induced an approximately sevenfold increase on CSF guanosine levels. Guanosine prevented the increase on spinal cord glutamate uptake induced by intraplantar capsaicin.


CONCLUSIONS
This study provides new evidence on the mechanism of action of the antinociceptive effects after systemic administration of guanosine. These effects seem to be related to the modulation of adenosine A(1) and A(2A) receptors and non-NMDA glutamate receptors.
Schmidt
A P
AP
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Böhmer
A E
AE
Schallenberger
C
C
Antunes
C
C
Tavares
R G
RG
Wofchuk
S T
ST
Elisabetsky
E
E
Souza
D O
DO
D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D006151:Guanosine / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism
D000700:Analgesics; D006151:Guanosine