title: Antihyperalgesic effect of tetrodotoxin in rat models of persistent muscle pain.
abstract: Persistent muscle pain is a common and disabling symptom for which available treatments have limited efficacy. Since tetrodotoxin (TTX) displays a marked antinociceptive effect in models of persistent cutaneous pain, we tested its local antinociceptive effect in rat models of muscle pain induced by inflammation, ergonomic injury and chemotherapy-induced neuropathy. While local injection of TTX (0.03-1 μg) into the gastrocnemius muscle did not affect the mechanical nociceptive threshold in naïve rats, exposure to the inflammogen carrageenan produced a marked muscle mechanical hyperalgesia, which was dose-dependently inhibited by TTX. This antihyperalgesic effect was still significant at 24h. TTX also displayed a robust antinociceptive effect on eccentric exercise-induced mechanical hyperalgesia in the gastrocnemius muscle, a model of ergonomic pain. Finally, TTX produced a small but significant inhibition of neuropathic muscle pain induced by systemic administration of the cancer chemotherapeutic agent oxaliplatin. These results indicate that TTX-sensitive sodium currents in nociceptors play a central role in diverse states of skeletal muscle nociceptive sensitization, supporting the suggestion that therapeutic interventions based on TTX may prove useful in the treatment of muscle pain.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Alvarez
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Electronic address: jon.levine@ucsf.edu.
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D063806:Myalgia / Q000188:drug therapy* / Q000503:physiopathology; D059226:Nociceptive Pain / Q000188:drug therapy / Q000503:physiopathology; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology*; D014110:Touch
chemical_list: D000700:Analgesics; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D013779:Tetrodotoxin
keywords: clinical trials; delayed-onset muscle soreness; inflammation; mechanical hyperalgesia; neuropathic muscle pain; voltage-dependent sodium channels