反复给予吗啡治疗导致的痛觉过敏、触诱发痛和脊髓神经胶质细胞激活可被选择性大麻素受体 2 型激动剂的共同给药所阻断。
Repeated morphine treatment-mediated hyperalgesia, allodynia and spinal glial activation are blocked by co-administration of a selective cannabinoid receptor type-2 agonist.
机构信息
Department of Pharmacology, The University of Arizona, Tucson, AZ 85724, USA.
出版信息
J Neuroimmunol. 2012 Mar;244(1-2):23-31. doi: 10.1016/j.jneuroim.2011.12.021. Epub 2012 Jan 30.
Abstract
Spinal glial activation has been implicated in sustained morphine-mediated paradoxical pain sensitization. Since activation of glial CB2 cannabinoid receptors attenuates spinal glial activation in neuropathies, we hypothesized that CB2 agonists may also attenuate sustained morphine-mediated spinal glial activation and pain sensitization. Our data indicate that co-administration of a CB2-selective agonist (AM 1241) attenuates morphine (intraperitoneal; twice daily; 6 days)-mediated thermal hyperalgesia and tactile allodynia in rats. A CB2 (AM 630) but not a CB1 (AM 251) antagonist mitigated this effect. AM 1241 co-treatment also attenuated spinal astrocyte and microglial marker and pro-inflammatory mediator (IL-1β, TNFα) immunoreactivities in morphine-treated rats, suggesting that CB2 agonists may be useful to prevent the neuroinflammatory consequences of sustained morphine treatment.
摘要
脊髓神经胶质细胞的激活被认为与持续的吗啡介导的矛盾性痛觉过敏有关。由于激活神经胶质细胞 CB2 大麻素受体可以减轻神经病理性疼痛中的脊髓神经胶质细胞的激活，因此我们假设 CB2 激动剂也可能减轻持续的吗啡介导的脊髓神经胶质细胞激活和痛觉过敏。我们的数据表明，CB2 选择性激动剂（AM 1241）的共同给药可减轻大鼠中吗啡（腹腔内；每天两次； 6 天）介导的热痛觉过敏和触觉异常。 CB2（AM 630）而不是 CB1（AM 251）拮抗剂减轻了这种作用。 AM 1241 的共同治疗还减轻了吗啡处理大鼠的脊髓星形胶质细胞和小胶质细胞标志物以及促炎介质（IL-1β，TNFα）的免疫反应性，表明 CB2 激动剂可能有助于预防持续吗啡治疗的神经炎症后果。
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