Honoré P, Buritova J, Chapman V, Besson J M
Physiopharmacologie du Système Nerveux, INSERM U.161 and EPHE, Paris, France.
Pain. 1998 Apr;75(2-3):281-93. doi: 10.1016/s0304-3959(98)00006-2.
The effects of oral administration of UP 202-56, an adenosine analogue, were assessed on carrageenan-induced spinal c-Fos protein expression and peripheral oedema. Three hours after intraplantar injection of carrageenan (6 mg/150 microl of saline), in awake rats, numerous c-Fos-like immunoreactive (c-Fos-LI) neurons in the dorsal horn of L4-L5 lumbar segments of the spinal cord (191 +/- 8; 184 +/- 10; 205 +/- 7 c-Fos-LI neurons per 40 microm section, for carrageenan controls in three experimental series performed in this study, respectively) and an extensive peripheral oedema were observed. Oral UP 202-56 (10, 30 or 50 mg/kg) dose-dependently reduced the number of carrageenan-induced c-Fos-LI neurons (r = 0.931. P < 0.0001), with the highest dose of UP 202-56 producing 72 +/- 4% reduction of the total number of carrageenan-induced spinal c-Fos-LI neurons, and 12 +/- 3% and 33 +/- 6% of reduction of control carrageenan oedema at paw and ankle levels, respectively. DPCPX (1 mg/kg i.p.), a selective adenosine A1 receptor antagonist, which injected alone had no effect on carrageenan-induced spinal c-Fos expression and peripheral oedema, blocked the effects of UP 202-56 (30 mg/kg p.o.) on the number of carrageenan-induced c-Fos-LI neurons. In addition, DPCPX did not modify the effects of UP 202-56 on carrageenan-induced peripheral oedema. DMPX (1 mg/kg i.p.), a somewhat selective adenosine A2 receptor antagonist, which injected alone had no significant effect on carrageenan-induced spinal c-Fos protein expression and peripheral oedema, did not influence the effects of UP 202-56 (30 mg/kg p.o.) on both carrageenan-induced spinal c-Fos expression and peripheral oedema. Our results demonstrate that UP 202-56 dose-dependently reduced the spinal c-Fos protein expression in carrageenan model of inflammatory pain. The ability of DPCPX to block the effect of UP 202-56, in contrast to the lack of effect of DMPX, increased evidence for a predominant role of adenosine A1 receptors activation in the mechanism of action of UP 202-56. These results increase evidence for a role of adenosine in the modulation of nociceptive transmission and support the antinociceptive action of adenosine analogues, such as UP 202-56, in inflammatory pain processes.
评估了口服腺苷类似物UP 202-56对角叉菜胶诱导的脊髓c-Fos蛋白表达和外周水肿的影响。在清醒大鼠足底注射角叉菜胶（6 mg/150 μl生理盐水）3小时后，观察到脊髓L4-L5腰段背角有大量c-Fos样免疫反应性（c-Fos-LI）神经元（在本研究进行的三个实验系列中，角叉菜胶对照组每40 μm切片分别有191±8、184±10、205±7个c-Fos-LI神经元），并伴有广泛的外周水肿。口服UP 202-56（10、30或50 mg/kg）剂量依赖性地减少了角叉菜胶诱导的c-Fos-LI神经元数量（r = 0.931，P < 0.0001），UP 202-56最高剂量使角叉菜胶诱导的脊髓c-Fos-LI神经元总数减少72±4%，在爪和踝关节水平对角叉菜胶诱导的水肿分别减少12±3%和33±6%。DPCPX（1 mg/kg腹腔注射）是一种选择性腺苷A1受体拮抗剂，单独注射对角叉菜胶诱导的脊髓c-Fos表达和外周水肿无影响，但能阻断UP 202-56（30 mg/kg口服）对角叉菜胶诱导的c-Fos-LI神经元数量的影响。此外，DPCPX不改变UP 202-56对角叉菜胶诱导的外周水肿的作用。DMPX（1 mg/kg腹腔注射）是一种 somewhat选择性腺苷A2受体拮抗剂，单独注射对角叉菜胶诱导的脊髓c-Fos蛋白表达和外周水肿无显著影响，也不影响UP 202-56（30 mg/kg口服）对角叉菜胶诱导的脊髓c-Fos表达和外周水肿的作用。我们的结果表明，在炎症性疼痛的角叉菜胶模型中，UP 202-56剂量依赖性地降低了脊髓c-Fos蛋白表达。与DMPX缺乏作用相反，DPCPX能够阻断UP 202-56的作用，这进一步证明了腺苷A1受体激活在UP 202-56作用机制中起主要作用。这些结果进一步证明了腺苷在伤害性传递调节中的作用，并支持腺苷类似物如UP 202-56在炎症性疼痛过程中的抗伤害感受作用。
