Supraspinal contribution to development of both tonic nociception and referred mirror hyperalgesia - A comparative study between formalin test and bee venom test in the rat

Background; The roles of descending facilitatory pathway from the rostral. medial medulla (RMM) in development of persistent spontaneous nociception and hyperalgesia were evaluated in the bee venom (BV) test and the formalin test. Methods. Bilateral lesions of the RMM with ibotenic acid, a soma-selective neurotoxin, were performed to study their effects on the spontaneous pain-related behaviors and hyperalgesia, which were determined by counting the number of flinching reflex per 5 min (1 h) and by measuring paw withdrawal thermal latency (PWTL) and mechanical threshold (PWMT) to radiant heat and von-Frey filaments to both hind paws in conscious rats, respectively. Results: 1) Bilateral lesions of the RMM produced a similarly significant inhibition of persistent spontaneous flinching reflexes in the BV test and the formalin test; however, the inhibitory effect occurred in the late 50 min (11-60 min), but not the first 10 min (0-10 min) following intraplantar injection of either BV or formalin. 2) Bilateral lesions of the RMM prevented the development of the BV-induced referred mirror heat hyperalgesia occurred in the noninjected paw, but had no effect on the primary heat and mechanical hyperalgesia occurred in the injected paw. Conclusions: The present results provide a new tine of behavioral evidence that tonic activation of descending facilitatory pathway contributes to the establishment of 1) the BV and formalin-induced persistent spontaneous nociception; and 2) the BV-induced referred mirror heat hyperalgesia and the central sensitization, but not the primary heat and mechanical hyperalgesia.