Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, CA 94143-0440, USA.
Ann Neurol. 2011 Jul;70(1):101-9. doi: 10.1002/ana.22382.
While inflammatory pain is well described in skeletal muscle, neuropathic muscle pain remains to be clarified. We used 3 well-established rodent models of peripheral neuropathy to evaluate for muscle pain.
In rats exposed to either of 2 neurotoxic cancer chemotherapies, paclitaxel or oxaliplatin, or to alcohol consumption, we assessed the evolution of mechanical hyperalgesia in skeletal muscle and skin, in the same animal. To explore the involvement of protein kinase C epsilon (PKCε), a second messenger implicated in some forms of neuropathic pain, antisense oligodeoxynucleotides (AS-ODNs) or mismatch ODNs (MM-ODNs) for PKCε were administered intrathecally.
Rats submitted to models of chemotherapy-induced and alcohol-induced neuropathy developed persistent muscle hyperalgesia, which evolved in parallel in muscle and skin. The administration of PKCε AS, which has been shown to mediate cutaneous hyperalgesia in paclitaxel and ethanol models of neuropathic pain, also inhibited muscle hyperalgesia induced by these agents. Stopping AS-ODN was associated with the reappearance of hyperalgesia at both sites. The AS-ODN to PKCε treatment was devoid of effect in both muscle and skin in the oxaliplatin neuropathy model.
Our results support the suggestion that neuropathic muscle pain may be a greater clinical problem than generally appreciated.
虽然骨骼肌肉中的炎性疼痛已有详细描述，但神经病理性肌肉疼痛仍需阐明。我们使用了 3 种已确立的周围神经病变啮齿动物模型来评估肌肉疼痛。
在接受紫杉醇或奥沙利铂这 2 种神经毒性癌症化疗药物或酒精摄入的大鼠中，我们评估了骨骼肌和皮肤中机械性痛觉过敏的演变情况，在同一只动物中进行评估。为了探讨蛋白激酶 C ɛ（PKCε）的参与，这种第二信使涉及某些形式的神经病理性疼痛，我们鞘内给予 PKCε 的反义寡核苷酸（AS-ODN）或错配 ODN（MM-ODN）。
接受化疗诱导和酒精诱导的神经病模型的大鼠发展出持续性肌肉痛觉过敏，在肌肉和皮肤中呈平行演变。已经显示在紫杉醇和乙醇诱导的神经病理性疼痛模型中，PKCε AS 介导了皮肤痛觉过敏，给予这种物质也抑制了这些药物引起的肌肉痛觉过敏。停止 AS-ODN 与这两个部位的痛觉过敏再次出现有关。奥沙利铂神经病变模型中，PKCε 的 AS-ODN 治疗对肌肉和皮肤均无影响。
我们的结果支持这样一种观点，即神经病理性肌肉疼痛可能是一个比普遍认为的更大的临床问题。
