Pregabalin suppresses spinal neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology.
Pregabalin suppresses spinal neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology.
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DOI：
10.1097/aln.0b013e31821f6545
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发表时间：
2011-07
期刊：
影响因子：
8.8
通讯作者：
Dickenson AH
中科院分区：
文献类型：
--
作者：
Bannister K;Sikandar S;Bauer CS;Dolphin AC;Porreca F;Dickenson AH
阿片样物质诱导的痛觉过敏在实验室和临床中得到认可，在没有外周病理学的情况下产生中枢兴奋过度。我们研究了普瑞巴林，适用于神经病理性疼痛，和昂丹司琼，一种药物，破坏在中枢神经系统中的下行多巴胺能处理，对脊髓神经元的过度兴奋和内脏高敏感性在阿片类药物诱导的痛觉过敏的大鼠模型。Sprague-Dawley大鼠（180-200 g）植入吗啡（90μg · μl-1 · hr-1）或盐水（0.9% w/v）填充的渗透微型泵。在异氟烷麻醉的动物中，第7-10天，我们评估了（a）全身性普瑞巴林对脊髓神经元和内脏运动反应的影响和（b）脊髓昂丹司琼对背角神经元反应的影响。B。分析各组大鼠背根神经节α2δ-1，5 HT 3A和μ阿片受体mRNA水平。在吗啡处理的动物中，诱发的脊髓神经元反应增强到热刺激和机械刺激的子集。普瑞巴林（至少71%）和昂丹司琼（37%）减弱了这种活性，普瑞巴林（52.8%）减弱了内脏对结肠直肠扩张压力子集的反应（所有测量n = 8，P < 0.05）。mRNA水平没有变化。普瑞巴林在阿片类药物诱导的痛觉过敏动物中的抑制作用不是神经病依赖性的，也不依赖于电压门控钙通道α2δ-1亚基的上调，这是普瑞巴林在神经病中的有效性所必需的机制。在阿片样物质诱导的痛觉过敏中，其延伸至结肠扩张，多巴胺能易化系统可能被上调，从而产生允许普瑞巴林介导的镇痛而无外周病理的环境。
Opioid induced hyperalgesia is recognised in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid induced hyperalgesia. Sprague-Dawley rats (180-200 g) were implanted with morphine (90μg · μl−1 · hr−1) or saline (0.9% w/v) filled osmotic mini-pumps. On days 7-10 in isoflurane anaesthetized animals we evaluated the effects of (a) systemic pregabalin on spinal neuronal and visceromotor responses and (b) spinal ondansetron on dorsal horn neuronal responses. The messenger RNA levels of α2δ-1, 5HT3A and mu-opioid receptor in the dorsal root ganglia of all animals were analysed. In morphine-treated animals the evoked spinal neuronal responses were enhanced to a sub-set of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%), and the visceromotor response to a sub-set of colorectal distension pressures was attenuated by pregabalin (52.8%) (n = 8 for all measures, P < 0.05). Messenger RNA levels were unchanged. The inhibitory action of pregabalin in opioid induced hyperalgesia animals is not neuropathy-dependent nor reliant on up-regulation of the α2δ-1 subunit of voltage gated calcium channels, mechanisms proposed essential for pregabalin’s efficacy in neuropathy. In opioid induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be upregulated creating an environment that’s permissive for pregabalin-mediated analgesia without peripheral pathology.