Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats.
To investigate whether ATP participates in spinal nociceptive transmission, effects of intrathecally applied P2-purinoceptor antagonists and agonists in the tail-flick and the formalin test were studied in rats. In the tail-flick assay, the P2 antagonists suramin (12-120 micrograms), Evans blue (0.1-10 micrograms), Trypan blue (1-30 micrograms) and Reactive blue 2 (1-30 micrograms) but not pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 0.03-30 micrograms) caused moderate antinociception up to a doubling of the response latency. In contrast, the P2 agonists alpha,beta-methylene ATP (alpha,beta-mATP, 0.3-30 micrograms) and 2-methylthio-ATP (3-30 micrograms) decreased the tail-flick latency by up to about 50%. When co-injected with alpha,beta-mATP, suramin (120 micrograms) or Evans blue (10 micrograms) prevented the effect of alpha,beta-mATP 3 micrograms but not of alpha,beta-mATP 30 micrograms. In the formalin test, pretreatment with suramin (3-90 micrograms) 60 min prior to testing caused significant antinociception by decreasing the weighted pain intensity score by up to about 80%. alpha,beta-mATP (30 micrograms), applied 30 min prior to testing, was without effect. The results indicate that endogenous ATP, acting through P2-purinoceptors, may contribute to nociceptive information processing in the spinal cord.
Driessen
B
B
Pharmakologisches Institut, Albert-Ludwigs-Universität Freiburg, Germany.
Reimann
W
W
Selve
N
N
Friderichs
E
E
Bültmann
R
R
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005557:Formaldehyde / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement; D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D058913:Purinergic Agonists; D058914:Purinergic Antagonists; D013873:Thionucleotides; D005557:Formaldehyde; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008501:2-methylthio-ATP