Cui J G, Sollevi A, Linderoth B, Meyerson B A
Department of Neurosurgery, Karolinska Institute/Hospital, Stockholm, Sweden.
Neurosci Lett. 1997 Feb 28;223(3):173-6. doi: 10.1016/s0304-3940(97)13435-8.
The aim of the present study was to investigate the intrathecal (i.t.) action of a selective A1-adenosine receptor agonist, R-phenylisopropyl adenosine (R-PIA), on tactile withdrawal thresholds in a rat model of mononeuropathy produced by sciatic chronic constriction injury (CCI). An additional aim was to examine whether adenosine receptor activation is involved in the effects of spinal cord stimulation (SCS), which activates low-threshold fibers and suppresses touch-evoked pain both in patients and in experimental animals with neuropathy. Animals presenting hindlimb withdrawal to von Frey filaments with a bending force of < 7.5 g on the lesioned side (compared to > or = 35 g in the normal limb), were considered as having tactile hypersensitivity ("allodynia'). R-PIA (1-10 nmol i.t.) induced a dose-dependent suppression of the tactile allodynia without producing impairment of motor function. The effect of R-PIA (3 nmol i.t.), a clearly submaximal dose, was abolished by concomitant treatment with the selective A1-adenosine receptor antagonist cyclopentylxanthine (10 nmol i.t.). In animals where SCS failed to influence tactile allodynia, concomitant i.t. administration of R-PIA (3 nmol) and SCS induced a clear-cut and long-lasting suppression of the hypersensitivity to tactile stimulation. In conclusion, adenosine receptor stimulation antagonizes tactile hypersensitivity in a CCI model of mononeuropathy and potentiates the action of spinal cord stimulation.
本研究的目的是探讨选择性A1-腺苷受体激动剂R-苯异丙基腺苷（R-PIA）在坐骨神经慢性压迫性损伤（CCI）所致单神经病大鼠模型中对触觉撤离阈值的鞘内（i.t.）作用。另一个目的是研究腺苷受体激活是否参与脊髓刺激（SCS）的效应，SCS可激活低阈值纤维并抑制患者及患有神经病的实验动物的触觉诱发疼痛。对病变侧用弯曲力<7.5 g的von Frey细丝刺激出现后肢撤离反应的动物（正常肢体>或 = 35 g），被认为具有触觉超敏反应（“异常性疼痛”）。R-PIA（1-10 nmol i.t.）可剂量依赖性地抑制触觉异常性疼痛，且不影响运动功能。R-PIA（3 nmol i.t.）这个明显低于最大剂量的效应，可被选择性A1-腺苷受体拮抗剂环戊基黄嘌呤（10 nmol i.t.）联合给药所消除。在SCS未能影响触觉异常性疼痛的动物中，鞘内联合给予R-PIA（3 nmol）和SCS可明显且持久地抑制对触觉刺激的超敏反应。总之，在单神经病的CCI模型中，腺苷受体刺激可拮抗触觉超敏反应并增强脊髓刺激的作用。
