Guanosine prevents thermal hyperalgesia in a rat model of peripheral mononeuropathy.
It is well known that adenine-based purines exert multiple effects on pain transmission. Less attention has been given, however, to the antinociceptive effects of guanine-based purines. The aim of this study was to investigate the effects of intraperitoneal administration of guanosine on a rat model of peripheral mononeuropathy. Additionally, investigation of the mechanism of action of guanosine, its general toxicity and measurements of central nervous system purine levels were performed. Rats received an intraperitoneal administration of vehicle (0.1 mM NaOH) or guanosine (up to 120 mg.kg(-1)) in an acute or chronic regimen. Guanosine significantly reduced thermal hyperalgesia on the ipsilateral side of the sciatic nerve ligation. Additionally, guanosine prevented locomotor deficits and body weight loss induced by the mononeuropathy. Acute systemic administration of guanosine caused an approximately 11-fold increase on central nervous system guanosine levels, but this effect was not observed after chronic treatment. Chronic guanosine administration prevented the increase on cortical glutamate uptake but not the decrease in spinal cord glutamate uptake induced by the mononeuropathy. No significant general toxicity was observed after chronic exposure to guanosine. This study provides new evidence on the mechanism of action of guanine-based purines, with guanosine presenting antinociceptive effects against a chronic pain model.


CONCLUSIONS
This study provides a new role for guanosine: chronic pain modulation. Guanosine presents as a new target for future drug development and might be useful for treatment of neuropathic pain.
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
Paniz
Lucas
L
Schallenberger
Cristhine
C
Böhmer
Ana Elisa
AE
Wofchuk
Susana T
ST
Elisabetsky
Elaine
E
Portela
Luis Valmor C
LV
Souza
Diogo O
DO
D000700:Analgesics / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006151:Guanosine / Q000134:cerebrospinal fluid / Q000494:pharmacology / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012585:Sciatica / Q000150:complications* / Q000188:drug therapy; D018709:Statistics, Nonparametric; D013997:Time Factors
D000700:Analgesics; D006151:Guanosine; D018698:Glutamic Acid