von Heijne M, Hao J X, Yu W, Sollevi A, Xu X J, Wiesenfeld-Hallin Z
Department of Cardiothoracic Anesthetics and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
Anesth Analg. 1998 Dec;87(6):1367-71.
We examined the development of tolerance to the antiallodynic effect of chronic intrathecal (IT) administration of the adenosine analog R-phenylisopropyladenosine (R-PIA) in a rat model of central pain after ischemic spinal cord injury. After 10 days of IT R-PIA treatment, the effect of IT morphine was also assessed to examine whether cross-tolerance between R-PIA and morphine was present. IT R-PIA completely alleviated allodynia-like behaviors to mechanical and cold stimuli in spinally injured rats. The anti-allodynic effect of R-PIA was maintained for 6-7 days with twice-daily administration and was reduced thereafter, particularly with respect to cold allodynia. IT morphine alleviated mechanical and cold allodynia in rats rendered tolerant to R-PIA to a degree comparable to that in R-PIA-naive (control) rats, which indicates that the anti-allodynic property of R-PIA is independent of the mechanisms by which morphine acts. The possibility of using agonists of adenosine receptors in treating refractory pain in patients with spinal cord injury is discussed.
There is often no satisfactory treatment for chronic pain after spinal cord injury. Our study suggests such pain can be treated with a spinal injection of R-phenylisopropyladenosine in rats. Reduced effect to R-phenylisopropyladenosine was noted with repeated administrations. However, there was no cross-tolerance to morphine.
我们在缺血性脊髓损伤后中枢性疼痛的大鼠模型中，研究了慢性鞘内注射腺苷类似物R-苯异丙基腺苷（R-PIA）抗痛觉过敏作用的耐受性发展情况。在鞘内注射R-PIA治疗10天后，还评估了鞘内注射吗啡的效果，以检查R-PIA和吗啡之间是否存在交叉耐受性。鞘内注射R-PIA可完全减轻脊髓损伤大鼠对机械和冷刺激的痛觉过敏样行为。R-PIA的抗痛觉过敏作用在每日两次给药时可维持6-7天，此后减弱，尤其是对冷痛觉过敏。鞘内注射吗啡可减轻对R-PIA产生耐受性的大鼠的机械和冷痛觉过敏，其程度与未用过R-PIA的（对照）大鼠相当，这表明R-PIA的抗痛觉过敏特性独立于吗啡的作用机制。本文讨论了使用腺苷受体激动剂治疗脊髓损伤患者顽固性疼痛的可能性。
脊髓损伤后的慢性疼痛通常没有令人满意的治疗方法。我们的研究表明，在大鼠中，这种疼痛可以通过鞘内注射R-苯异丙基腺苷来治疗。重复给药后，对R-苯异丙基腺苷的效果有所降低。然而，对吗啡没有交叉耐受性。
