Roles of adenosine and serotonin receptors on the antinociception of sildenafil in the spinal cord of rats.
OBJECTIVE
The phosphodiesterase 5 inhibitor sildenafil has antinociceptive effects, mediated by an increase in cGMP. This study examined the role of spinal adenosine and serotonin receptors played in the antinociceptive effects of intrathecal sildenafil.


METHODS
Intrathecal catheters were inserted into the subarachnoid space of Sprague-Dawley male rats as a drug delivery device. Pain was induced by injecting formalin into the plantar surface of rats and observing nociceptive behavior (flinching response) for 60 minutes. Then, the effects of intrathecal adenosine and serotonin receptor antagonists on the antinociceptive activity of intrathecal sildenafil were examined.


RESULTS
Intrathecal sildenafil suppressed the flinching response in a dose-dependent manner during phases 1 and 2 in the formalin test. Both CGS 15943 and dihydroergocristine decreased the antinociceptive effects of sildenafil during phases 1 and 2 in the formalin test.


CONCLUSIONS
Intrathecal sildenafil effectively attenuated the pain evoked by formalin injection. Both adenosine and serotonin receptors may be involved in the antinociceptive action of sildenafil at the spinal level.
Lee
Hyung Gon
HG
Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Dong-gu, Gwangju, Korea.
Kim
Woong Mo
WM
Park
Cheon Hee
CH
Yoon
Myung Ha
MH
D000241:Adenosine / Q000378:metabolism; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D025442:Dihydroergocristine / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D000068677:Sildenafil Citrate; D013116:Spinal Cord / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000627:therapeutic use
D000700:Analgesics; D010879:Piperazines; D011687:Purines; D018047:Receptors, Purinergic P1; D011985:Receptors, Serotonin; D013450:Sulfones; D014665:Vasodilator Agents; D025442:Dihydroergocristine; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D000241:Adenosine