Muscle Pain in Models of Chemotherapy- and Alcohol-induced Peripheral Neuropathy

Objective—While inflammatory pain is well described in skeletal muscle, neuropathic muscle pain remains to be clarified. We used three well-established rodent models of peripheral neuropathy to evaluate for muscle pain. Methods—In rats exposed to either of two 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, oligodeoxynucleotides (ODN) antisense (AS) or mismatch (MM) for PKCε were administered intrathecally. Results—Rats submitted to models of chemotherapyand 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. Interpretation—Our results support the suggestion that neuropathic muscle pain may be a greater clinical problem than generally appreciated.