Synergistic antinociception of intrathecal sildenafil with clonidine in the rat formalin test.
Spinal sildenafil (phosphodiesterase 5 inhibitor) and clonidine (alpha-2 adrenoceptor agonist) have shown antinociception. The author examined the properties of drug interaction after concurrent administration of intrathecal sildenafil-clonidine, and further clarified the reciprocity of sildenafil and clonidine. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. The formalin test was used as a nociceptive test, which was induced by subcutaneous injection of 50 microl of 5% formalin solution into the hindpaw. The pharmacological interaction was characterized using an isobolographic analysis. Intrathecal sildenafil and clonidine dose-dependently suppressed the flinching response observed during phase 1 and phase 2 in the formalin test. Isobolographic analysis revealed a synergistic interaction after intrathecal delivery of sildenafil-clonidine in both phases. Intrathecal yohimbine antagonized the antinociceptive action of intrathecal sildenafil during both phases in the formalin test. However, intrathecal ODQ failed to antagonize the antinociceptive action of intrathecal clonidine. These results suggest that sildenafil and clonidine, and the mixture of the two are effective against acute pain and facilitated pain state at the spinal level. Furthermore, synergism was noted after delivery of sildenafil-clonidine mixture. The antinociception of sildenafil can be modulated by spinal alpha-2 adrenoceptor, while the effect of clonidine is independent on the guanyly cyclase.
Yoon
Myung Ha
MH
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, South Korea. mhyoon@chonnam.ac.kr
Kim
Chang Mo
CM
Lee
Hyung Gon
HG
Kim
Woong Mo
WM
An
Tae Hoon
TH
Kim
Yeo Ok
YO
Huang
Lan Ji
LJ
D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006162:Guanylate Cyclase / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D010147:Pain Measurement; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*
D000700:Analgesics; D010879:Piperazines; D011687:Purines; D018341:Receptors, Adrenergic, alpha-2; D013450:Sulfones; D000068677:Sildenafil Citrate; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D003000:Clonidine