title: Muscle pain in models of chemotherapy-induced and alcohol-induced peripheral neuropathy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our results support the suggestion that neuropathic muscle pain may be a greater clinical problem than generally appreciated.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California, San Francisco, San Francisco, CA 94143-0440, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alvarez
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Ferrari
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000473:pathology; D020269:Alcoholic Neuropathy / Q000209:etiology / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D010146:Pain / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents