Cannabinoid CB2 receptor (CB2r) agonists are potential painkillers void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2r, however the involvement of CB2r from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2r agonist JWH133 in wild-type and knockout mice lacking CB2r in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2r disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2r knockouts and was increased in mice defective in neuronal CB2r knockouts suggestive of increased spontaneous pain. Interestingly, CB2r-positive lymphocytes infiltrated the injured nerve and possible CB2r transfer from immune cells to neurons was found. Lymphocyte CB2r depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB2r that protects against spontaneous and evoked neuropathic pain.

中文翻译：

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神经和淋巴大麻素CB2受体在神经性疼痛中的保护作用

大麻素CB2受体（CB2r）激动剂是潜在的止痛药，没有精神作用。外周免疫细胞，神经元和神经胶质细胞表达CB2r，但是仍未解决这些细胞中CB2r参与神经性疼痛的问题。我们通过在野生型和基因敲除小鼠中缺乏CB2r的野生型和敲除小鼠中的选择性CB2r激动剂JWH133的按需自我给药，探索了自发性神经性疼痛。自我管理可反映出服用药物可减轻自发性疼痛，伤害性和情感性表现。虽然CB2r的组成型缺失破坏了JWH133的摄取行为，但这种行为在单核细胞特异性CB2r敲除中并未改变，而在神经元CB2r敲除缺陷的小鼠中却增加了，提示了自发性疼痛增加。有趣的是 CB2r阳性淋巴细胞浸润了受伤的神经，并发现了可能的CB2r从免疫细胞转移到神经元。淋巴细胞CB2r的消耗也会加剧JWH133的自我给药并抑制抗伤害感受。这项工作确定了神经元和淋巴CB2r的同时活动，可防止自发性和诱发性神经性疼痛。