Yonsei Med J.  2010 Nov;51(6):960-964. 10.3349/ymj.2010.51.6.960.

Roles of Adenosine and Serotonin Receptors on the Antinociception of Sildenafil in the Spinal Cord of Rats

• Lee HG
• Kim WM
• Park CH
• Yoon MH

• KMID: 1779647
• DOI: http://doi.org/10.3349/ymj.2010.51.6.960

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.

Keyword

Adenosine; antinociception; serotonin; sildenafil; spinal cord

MeSH Terms

Adenosine/metabolism
Analgesics/*therapeutic use
Animals
Cyclic GMP/metabolism
Dihydroergocristine/pharmacology
Injections, Spinal
Male
Pain/*drug therapy
Piperazines/*pharmacology
Purines/pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P1/*metabolism
Receptors, Serotonin/*metabolism
Spinal Cord/*metabolism
Sulfones/*pharmacology
Vasodilator Agents/therapeutic use

Figure

• 

  Fig. 1 Time-effect curve of sildenafil on flinching in the formalin test. Sildenafil was administered intrathecally at time - 10 min and the formalin was injected subcutaneously at time 0. Data are presented as the number of flinches. Each line represents mean ± SEM.

• 

  Fig. 2 Dose-response curve of intrathecal sildenafil on the flinching during phases 1 (A) and 2 (B) in the formalin test. Data are presented as the sum of the number of flinches in each phase. Intrathecal sildenafil produced dose-dependent suppression of flinching in both phases. Each line represents mean ± SEM. Compared with the control [dimethylsulfoxid (DMSO)]. *p < 0.05.

• 

  Fig. 3 The antagonistic effects of intrathecal CGS 15943 (adenosine receptor antagonist, 0.03 µg) and dihydroergocristine (HEC, serotonin receptor antagonist, 3 µg) on the antinociceptive effects of intrathecal sildenafil (30 µg) during phases 1 (A) and 2 (B) in the formalin test. The two antagonists and sildenafil were given 20 or 10 min respectively before injecting formalin. The data are presented as the sum of the number of flinches in each phase. Each bar represents mean ± SEM. Compared with sildenafil (30 µg): *p < 0.05, †p < 0.01.

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