Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury.
Endogenous analgesic action of the pontospinal noradrenergic system spatially restricts and temporally delays the progression of neuropathic pain following tibial nerve injury.
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DOI：
10.1016/j.pain.2013.05.010
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发表时间：
2013-09
期刊：
影响因子：
7.4
通讯作者：
Pickering AE
中科院分区：
文献类型：
--
作者：
Hughes SW;Hickey L;Hulse RP;Lumb BM;Pickering AE
脑桥脊髓去甲肾上腺素能系统在神经损伤模型中动态限制神经病理性疼痛表型时空表达的作用。脑桥脊髓去甲肾上腺素能神经元形成抑制急性疼痛的内源性镇痛系统的一部分，但关于其在神经病理性疼痛中的作用有相互矛盾的证据。我们研究了胫神经切断（TNT）后大鼠神经病理性疼痛表型发展过程中去甲肾上腺素能控制下降的时序。在神经损伤时植入腰椎鞘内套管，允许给予选择性α-肾上腺素受体（α-AR）拮抗剂，以连续测定其对异常性疼痛和痛觉过敏表达的影响。TNT治疗后，动物逐渐出现机械性和冷异常性疼痛（第10天），随后出现热过敏（第17天）。鞘内注射育亨宾（30 μg）阻断α2-AR，可使同侧所有方式的致敏作用提前，而哌唑嗪（30 μg，α1-AR）则无此作用。建立的异常性疼痛（到第21天）被再摄取抑制剂reboxaline（5 μg，i.t.）但育亨宾不再有任何致敏作用。这种效果的丧失与同侧腰椎背角下行去甲肾上腺素能神经支配的减少相一致。育亨宾可逆地揭示了对侧后肢异常性疼痛和痛觉过敏的所有方式和增加背角c-fos表达一个无害的刷刺激。育亨宾给药在接触热斜坡范例中也可逆地发现了麻醉TNT大鼠的外侧热痛觉过敏。在TNT之后，存在抑制性α2-AR介导的去甲肾上腺素能紧张性的参与，其完全掩盖对侧并短暂抑制同侧敏化的发展。这种内源性镇痛系统在神经损伤后形成神经病理性疼痛表型的空间和时间表达中起关键作用。
A role for the pontospinal noradrenergic system to dynamically restrict the spatiotemporal expression of the neuropathic pain phenotype in a nerve injury model. Pontospinal noradrenergic neurons form part of an endogenous analgesic system that suppresses acute pain, but there is conflicting evidence about its role in neuropathic pain. We investigated the chronology of descending noradrenergic control during the development of a neuropathic pain phenotype in rats following tibial nerve transection (TNT). A lumbar intrathecal cannula was implanted at the time of nerve injury allowing administration of selective α-adrenoceptor (α-AR) antagonists to sequentially assay their effects upon the expression of allodynia and hyperalgesia. Following TNT animals progressively developed mechanical and cold allodynia (by day 10) and subsequently heat hypersensitivity (day 17). Blockade of α2-AR with intrathecal yohimbine (30 μg) revealed earlier ipsilateral sensitization of all modalities while prazosin (30 μg, α1-AR) was without effect. Established allodynia (by day 21) was partly reversed by the re-uptake inhibitor reboxetine (5 μg, i.t.) but yohimbine no longer had any sensitising effect. This loss of effect coincided with a reduction in the descending noradrenergic innervation of the ipsilateral lumbar dorsal horn. Yohimbine reversibly unmasked contralateral hindlimb allodynia and hyperalgesia of all modalities and increased dorsal horn c-fos expression to an innocuous brush stimulus. Contralateral thermal hyperalgesia was also reversibly uncovered by yohimbine administration in a contact heat ramp paradigm in anaesthetised TNT rats. Following TNT there is an engagement of inhibitory α2-AR-mediated noradrenergic tone which completely masks contralateral and transiently suppresses the development of ipsilateral sensitization. This endogenous analgesic system plays a key role in shaping the spatial and temporal expression of the neuropathic pain phenotype after nerve injury.
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影响因子：
2.5
作者：
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通讯作者：
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