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: P Alvarez, J D Levine
• Journal: Neuroscience (Neuroscience) Vol. 311 Pg. 499-507 (Dec 17 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 26548414 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Analgesics
• Organoplatinum Compounds
• Oxaliplatin
• Tetrodotoxin

Topics

• Analgesics (pharmacology)
• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hyperalgesia (drug therapy, physiopathology)
• Male
• Motor Activity (drug effects, physiology)
• Muscle, Skeletal (drug effects, physiopathology)
• Myalgia (drug therapy, physiopathology)
• Nociceptive Pain (drug therapy, physiopathology)
• Organoplatinum Compounds
• Oxaliplatin
• Pain Threshold (drug effects, physiology)
• Rats, Sprague-Dawley
• Tetrodotoxin (pharmacology)
• Touch