Descending facilitatory pathways from the RVM initiate and maintain bilateral hyperalgesia after muscle insult

Abstract

Initiated and maintained by activation of descending facilitatory pathways from the RVM. Male Sprague–Dawley rats were implanted with intracerebral guide cannulae into the nucleus raphe magnus (NRM) or the nucleus gigantocellularis (Gi). Two injections of acidic saline into one gastrocnemius muscle 5 days apart lead to robust hyperalgesia after the second injection. Either ropivacaine (local anesthetic) or vehicle (control) was microinjected into the RVM prior to the first intramuscular acid injection, prior to the second injection, or 24 h after the second injection. Mechanical withdrawal thresholds of the paw (von Frey filaments) and the muscle (tweezer) were measured before and 24 h after induction of hyperalgesia. The withdrawal thresholds for both the paw (cutaneous secondary hyperalgesia) and muscle (primary hyperalgesia) were decreased 24 h after the second intramuscular acid injection in the vehicle control groups. Administration of ropivacaine prior to the first intramuscular acid injection had no effect on development of either cutaneous or muscle hyperalgesia that develops after the second injection. However, neither cutaneous nor muscle hyperalgesia developed in the group treated with ropivacaine prior to the second intramuscular injection. Ropivacaine also significantly reversed the hyperalgesia in the group treated 24 h after the second intramuscular acid injection. Thus, the RVM is critical for both the development and maintenance of hyperalgesia after muscle insult....