Antinociceptive Effect of Botulinum Toxin A in Persistent Muscle Pain Rat Model

OBJECTIVE: To investigate the effects of botulinum toxin on the mechanical hyperalgesia, electrophysiology and motor functions in the persistent muscle pain rat model. METHOD: A secondary mechanical hyperalgesia in the bilateral hindpaws of Sprague-Dawley rats was produced by the repeated injections of acidic saline into gastrocnemius. Botulinum toxin A (BTX-A(4): 4 U/kg, BTX-A(7): 7 U/kg) was administrated into same muscle 24 hours after a second injection of saline. The mechanical hyperalgesia was measured with withdrawal threshold to von Frey filament. The grade of muscle paralysis was evaluated with electrophysiology and the locomotor performance using inclined plane board. RESULTS: The mechanical hyperalgesia was significantly decreased from 5 days to 2 weeks in BTX-A(7) group in the injected side. The dose-dependent decreased amplitude of compound muscle action potential and reduced prevalence of endplate noise from the first day of botulinum toxin injection lasted for 4 weeks in both gastrocnemius. The maximum angle maintained at initial position on the inclined plane board did not change. CONCLUSION: Local muscular injection of botulinum toxin A reduced ipsilateral hyperalgesia dose-dependently in persistent muscle pain rat model without motor deficit. The antinociceptive mechanism of botulinum toxin might act at a local or peripheral rather than a systemic or central effect due to ineffectiveness of contralateral hyperalgesia. Clinically, botulinum toxin A might be useful for the treatment of local and referred pain of muscle origins.

The Effect of Low-Level Laser Irradiation on Activities of Dorsal Horn Neurons in Rats with Experimental Muscle Pain

OBJECTIVE: This study was performed to investigate the effects of low-level laser irradiation on the dorsal horn cell activities in the rats with experimental muscle pain. METHOD: Experimental muscle pain was induced by repeated injections of acidic saline into the gastrocnemius muscle in thirty Sprague-Dawley rats. Activities of ipsilateral dorsal horn cells were recorded with a glass microelectrode at L2-L4 spinal cord level before and after low-level laser irradiation on the injected leg. Cells were categorized as wide dynamic range (WDR) and high threshold (HT) cells by the response to the cotton, vonFrey filament, and forceps stimulation at the receptive area. RESULTS: The spontaneous and mechanically evoked activities of WDR and HT cells were significantly increased in the muscle pain models. Low-level laser irradiation reduced mechanically evoked activities of WDR and HT cells. This effect was maximal at 20 minutes after irradiation and then returned to pre-treatment level in 40~50 minutes. CONCLUSION: The low-level laser irradiation was effective for the management of muscle pain by reducing activities of dorsal horn cells. Low-level laser might be clinically used for the treatment of local and referred pain of muscle origin.

The Mechanism of Contralateral Hyperalgesia in the Persistent Muscle Pain Rat Model

OBJECTIVE: This study was designed to investigate the mechanism of the primary afferent input to spread of contralateral hyperalgesia in the persistent muscle pain model in the rat. METHOD: Muscle pain was induced by twice repeated intramuscular injections of pH 6.0 buffered saline into the unilateral gastrocnemius muscle of the rats. Change of mechanical withdrawal threshold to von-Frey filament was measured after ipsilateral laser irradiation, anesthetic blockade with lidocaine and dorsal rhizotomy (L2~L6) to reduce primary afferent input from the tissue injury. RESULTS: Bilateral persistent mechanical hyperalgesia in the hind paw was evoked after second injection. Ipsilateral laser irradiation, lidocaine injection and dorsal rhizotomy had no effect on the contralateral spread of mechanical hyperalgesia. CONCLUSION: These results suggest that contralateral hyperalgesia was produced by, but didn't need to be maintained by inputs from an injury. Therefore, central nervous systems are responsible for the contralateral spread of hyperalgesia.

Development and Assessment of Animal Model of Persistent Muscle Pain

OBJECTIVE: The purposes of this study were the development and assessment of an animal model of persistent muscle pain induced by repeated intramuscular injections of low pH buffered saline. METHOD: Buffered saline at pH 4, 6 or 7.2 were injected twice, 3 days apart, into the gastrocnemius muscles of thirty Sprague-Dawley rats. To quantify hyperalgesia, paw withdrawal response to von Frey filament (mechanical hyperalgesia) and acetone (cold hyperalgesia) were measured for the 4 weeks after injection. Also the locomotor performance with inclined plane board and treadmill, and electrophysiologic study were evaluated. RESULTS: Mechanical hyperalgesia that was produced by the single injection of saline lasted less than 24 hours. The repeated injection of acidic saline produced mechanical hyperalgesia for more than 4 weeks at injected side and 3 weeks at contralateral side. Cold hyperalgesia lasted for 1 week after injection bilaterally. The locomotor performance and nerve conduction studies were not changed after injection. CONCLUSION: We have developed and characterized a model of muscular pain that was long lasting and widespread. This might prove useful for studying pain of muscular origin that may be similar to the chronic pain syndromes observed clinically.