Department of Pain Research, Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Behav Brain Res. 2012 Jan 1;226(1):242-9. doi: 10.1016/j.bbr.2011.09.023. Epub 2011 Sep 17.
The reserpine-induced myalgia (RIM) rat manifests fibromyalgia-like chronic pain symptoms. The present study explored the pathophysiology underlying the pain symptoms in the RIM rat and the chronic constriction injury (CCI) rat, an animal model of neuropathic pain as a reference. Nerve tissue samples were collected from the nociception-tested animals for pathological examinations. Additionally, the therapeutic efficacy of a sodium channel blocker mexiletine was assessed in both rats. A slight vacuolization in the substantia nigra (SN) occurred in some of the RIM rats without any other histopathological changes in the brain or peripheral neurons. All the RIM rats, with or without vacuolization, showed hypersensitivity to tactile, muscle pressure, and cold stimuli. In the CCI rat, neurodegenerative changes were apparent in the sciatic nerve and the spinal cord only. CCI rats displayed muscle hyperalgesia in addition to tactile and cold allodynia. Pharmacotherapy with mexiletine did not attenuate the pain in the RIM rat, although it was effective in the CCI rat. Taken together, it is not likely that pain symptoms in RIM rats are caused by degenerative changes at the level of primary afferents and spinal cord, as is the case for CCI rats. The significance of the vacuolization in the SN is less clear at present because of the minor extent of the change and the lack of correlation with nociceptive sensitivity. The pain symptoms in RIM rats could be associated with dysfunction of biogenic amines-mediated CNS pain control even without apparent pathologies in the nervous system.
利血平诱导的肌肉痛（RIM）大鼠表现出类似纤维肌痛的慢性疼痛症状。本研究探讨了 RIM 大鼠和慢性缩窄性损伤（CCI）大鼠疼痛症状的病理生理学基础，CCI 大鼠是神经病理性疼痛的动物模型。从接受疼痛测试的动物身上采集神经组织样本进行病理检查。此外，评估了钠离子通道阻滞剂美西律对这两种大鼠的治疗效果。一些 RIM 大鼠的黑质（SN）出现轻微空泡化，但大脑或周围神经元没有其他组织病理学变化。所有 RIM 大鼠，无论是否有空泡化，对触觉、肌肉压力和冷刺激均表现出超敏反应。在 CCI 大鼠中，只有坐骨神经和脊髓出现神经退行性变化。CCI 大鼠除了触觉和冷感觉过敏外，还表现出肌肉痛觉过敏。美西律的药物治疗并未减轻 RIM 大鼠的疼痛，尽管它对 CCI 大鼠有效。综上所述，RIM 大鼠的疼痛症状不太可能是由于初级传入和脊髓水平的退行性变化引起的，而 CCI 大鼠则是这种情况。目前，SN 中的空泡化的意义尚不清楚，因为变化程度较小，且与痛觉敏感性缺乏相关性。RIM 大鼠的疼痛症状可能与生物胺介导的中枢神经系统疼痛控制功能障碍有关，即使神经系统没有明显的病理学变化。
