ziconotide and Burns

Various animal models of pain are dependent on activation of different glutamate receptor subtypes. First degree burn of the paw elicits a secondary hyperalgesia that is dependent on Ca2+ permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not N-methyl-D-aspartate (NMDA) receptors. The present study takes advantage of that specificity by examining the effects of spinal pretreatments of agents on this secondary hyperalgesia. Rats with indwelling intrathecal catheters were pretreated with agents prior to paw injury. Mechanical withdrawal thresholds were measured before, and for three h after the injury. Spinal pretreatment with cyclooxygenase (10 and 30 microg (S)-(+)-ibuprofen; and 3 and 30 microg ketorolac) and nitric oxide synthase (33 and 100 microg N(G) Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 10 microg thiocitrulline) inhibitors resulted in no specific anti-allodynia. In contrast, ziconotide (0.3, 1.0 and 3 microg), the N-type voltage gated calcium channel antagonist was very effective in blocking burn-induced sensitivity at all doses used. l-type (Diltiazam 230 microg) and P-type (Agatoxin IVA 0.3 microg) calcium channel blockers produced intermediate effects. Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca2+ permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre- or post-synaptically.

Topics: Animals; Behavior, Animal; Burns; Calcium Channel Blockers; Cyclooxygenase Inhibitors; Diltiazem; Enzyme Inhibitors; Hyperalgesia; Ibuprofen; Injections, Spinal; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; omega-Conotoxins; Pain Measurement; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Spinal Cord; Verapamil