Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea.
Neurosci Lett. 2010 Aug 23;480(3):182-5. doi: 10.1016/j.neulet.2010.06.025. Epub 2010 Jun 12.
We recently found that the antinociceptive effects produced by intrathecal administration of sildenafil, a phosphodiesterase 5 inhibitor, were reversed by a nonspecific adenosine receptor antagonist, suggesting that adenosine receptors are involved in sildenafil-induced antinociception. Four adenosine receptor subtypes have been identified: A(1), A(2A), A(2B), and A(3). We examined the involvement of spinal adenosine receptor subtypes in the antinociceptive effects of intrathecal sildenafil. Intrathecal catheters were implanted in male SD rats, and nociception was assessed using the formalin test, which consisted of a subcutaneous injection of 50 microl of 5% formalin solution into the hind paw. We examined the effects of an adenosine A(1) receptor antagonist (CPT), an adenosine A(2A) receptor antagonist (CSC), an adenosine A(2B) receptor antagonist (alloxazine), and an adenosine A(3) receptor antagonist (MRS 1220) on sildenafil-induced antinociception. Intrathecal sildenafil suppressed formalin-induced flinching during phases 1 and 2 of the test in a dose-dependent manner. Intrathecal CPT, CSC, alloxazine, and MRS 1220 all suppressed the antinociceptive effects of sildenafil during both phases of the formalin test. These results suggest that sildenafil is an effective treatment for acute pain and the facilitated pain state at the spinal level. Additionally, spinal adenosine A(1), A(2A), A(2B), and A(3) receptors may play a role in sildenafil-induced antinociception.
我们最近发现，鞘内给予磷酸二酯酶 5 抑制剂西地那非产生的镇痛作用被非特异性腺苷受体拮抗剂逆转，这表明腺苷受体参与了西地那非诱导的镇痛作用。已经鉴定出四种腺苷受体亚型：A(1)、A(2A)、A(2B)和 A(3)。我们研究了脊髓腺苷受体亚型在鞘内西地那非的镇痛作用中的参与。在雄性 SD 大鼠中植入鞘内导管，并使用福尔马林测试评估痛觉，该测试包括将 50 微升 5%福尔马林溶液皮下注射到后爪中。我们研究了腺苷 A(1)受体拮抗剂 (CPT)、腺苷 A(2A)受体拮抗剂 (CSC)、腺苷 A(2B)受体拮抗剂 (alloxazine) 和腺苷 A(3)受体拮抗剂 (MRS 1220) 对西地那非诱导的镇痛作用的影响。鞘内西地那非以剂量依赖性方式抑制测试的 1 相和 2 相期间的福尔马林引起的退缩。鞘内 CPT、CSC、alloxazine 和 MRS 1220 均抑制了福尔马林测试的两个阶段中西地那非的镇痛作用。这些结果表明，西地那非是治疗急性疼痛和脊髓水平促进疼痛状态的有效治疗方法。此外，脊髓腺苷 A(1)、A(2A)、A(2B)和 A(3)受体可能在西地那非诱导的镇痛作用中发挥作用。
