Roles of Adenosine and Serotonin Receptors on the Antinociception of Sildenafil in the Spinal Cord of Rats
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Purpose: 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. Materials and 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 mininutes. 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. Conclusion: 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.
Abstract
Purpose: 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. Materials and 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 mininutes. 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. Conclusion: 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.
참고문헌 (31)
- Gibson A, "Phosphodiesterase 5 inhibitors and nitrergic transmission-from zaprinast to sildenafil", Eur J Pharmacol, 411, pp.1~10 (2001)
- Mixcoatl-Zecuatl T, "Sildenafil produces antinociception and increases morphine antinociception in the formalin test", Eur J Pharmacol, 400, pp.81~87 (2000)
- Asomoza-Espinosa R, "Sildenafil increases diclofenac antinociception in the formalin test", Eur J Pharmacol, 418, pp.195~200 (2001)
- Araiza-Saldaña CI, "Effect of diabetes on the mechanisms of intrathecal antinociception of sildenafil in rats", Eur J Pharmacol, 527, pp.60~70 (2005)
- Yoon MH, "Roles of opioid receptor subtypes on the antinociceptive effect of intrathecal sildenafil in the formalin test of rats", Neurosci Lett, 441, pp.125~128 (2008)
- Jain NK, "Sildenafil-induced peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway", Brain Res, 909, pp.170~178 (2001)
- Jain NK, "Sildenafil, a phosphodiesterase-5 inhibitor, enhances the antinociceptive effect of morphine", Pharmacology, 67, pp.150~156 (2003)
- Vale ML, "Role of NO", cGMP, Inflamm Res, pp.2007, 56[DOI]
- Patil CS, "Peripheral and central activation of nitric oxide-cyclic GMP pathway by sildenafil", Inflammopharmacology, 13, pp.467~478 (2005)
- 김웅모, "쥐의 포르말린 시험에서 척수강 Sildenafil의 항통각효과에 대한 GABAB 수용체 조절성", The Korean Journal of Pain, 20(2), pp.4~4 (2007), 대한통증학회
- Sawynok J, "Adenosine in the spinal cord and periphery:release and regulation of pain", Prog Neurobiol, 69, pp.313~340 (2003)
- Jacobson KA, "Adenosine receptors as therapeutic targets", Nat Rev Drug Discov, 5, pp.247~264 (2006)
- Fürst S, "Transmitters involved in antinociception in the spinal cord", Brain Res Bull, 48, pp.129~141 (1999)
- Yoon MH, "Antinociception of intrathecal adenosine receptor subtype agonists in rat formalin test", Anesth Analg, 101, pp.1417~1421 (2005)
- Jeong CY, "Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats", Eur J Pharmacol, 502, pp.205~211 (2004)
- Zahn PK, "Adenosine A1 but not A2a receptor agonist reduces hyperalgesia caused by a surgical incision in rats: a pertussis toxin-sensitive G proteindependent process", Anesthesiology, 107, pp.797~806 (2007)
- Qu CL, "The role of 5-HT receptor subtypes in the ventrolateral orbital cortex of 5-HT-induced antinociception in the rat", Neuroscience, 152, pp.487~494 (2008)
- Akula KK, "Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice", Eur J Pharmacol, 587, pp.129~134 (2008)
- Santos-Silva AJ, "PDE4 and PDE5 regulate cyclic nucleotides relaxing effects in human umbilical arteries", Eur J Pharmacol, 582, pp.102~109 (2008)
- Yaksh TL, "Chronic catheterization of the spinal subarachnoid space", Physiol Behav, 17, pp.1031~1036 (1976)
- MyungHaYoon, "Spinal Gabapentin and Antinociception: Mechanisms of Action", Journal of Korean Medical Science, 18(2), pp.255~261 (2003), 대한의학회
- Yoon MH, "Antinociception of intrathecal cholinesterase inhibitors and cholinergic receptors in rats", Acta Anaesthesiol Scand, 47, pp.1079~1084 (2003)
- Beavo JA, "Primary sequence of cyclic nucleotide phosphodiesterase isozymes and the design of selective inhibitors", Trends Pharmacol Sci, 11, pp.150~155 (1990)
- Uckert S, "Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future", Eur Urol, 50, pp.1194~1207 (2006)
- Pyne NJ, "cGMP signal termination", Biochem Soc Trans, 24, pp.1019~1022 (1996)
- Beavo JA, "Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms", Physiol Rev, 75, pp.725~748 (1995)
- Ferreira SH, "I - Prostaglandin hyperalgesia, a cAMP", Ca2+ dependent process, 1979, pp.18, 179~190
- Sousa AM, "The dual effect of a nitric oxide donor in nociception", Brain Res, 897, pp.9~19 (2001)
- Tegeder I, "Dual effects of spinally delivered 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) in formalin-induced nociception in rats", Neurosci Lett, 332, pp.146~150 (2002)
- Choca JI, "Adenosine A1 and A2 receptors of the substantia gelatinosa are located predominantly on intrinsic neurons: an autoradiography study", J Pharmacol Exp Ther, 247, pp.757~764 (1988)
- Barnes NM, "A review of central 5-HT receptors and their function", Neuropharmacology, 38, pp.1083~1152 (1999)