Secondary hyperalgesia in the rat first degree burn model is independent of spinal cyclooxygenase and nitric oxide synthase

Abstract

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 Ca 2++ permeable α-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 μg (S)-(+)-ibuprofen; and 3 and 30 μg ketorolac) and nitric oxide synthase (33 and 100 μg N G Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 10 μg thiocitrulline) inhibitors resulted in no specific anti-allodynia. In contrast, ziconotide (0.3, 1.0 and 3 μg), the N-type voltage gated calcium channel antagonist was very effective in blocking burn-induced sensitivity at all doses used. L-type (Diltiazam 230 μg) and P-type (Agatoxin IVA 0.3 μg) calcium channel blockers produced intermediate effects. Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca 2++ permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre-or post-synaptically.

Intrathecal P/Q- and R-type calcium channel blockade of spinal substance P release and c-Fos expression

“…Correspondence with the supplier indicated data showing purity and appropriate amino acid content (Dr. Watanabe from Peptide Institute, Inc.). We noticed that doses exceeding 0.5 µg caused severe side effects such as involuntary spasm, sudden burst of scratching, jumping followed by motor weakness and depression of breathing, symptoms also reported in previous studies (Malmberg and Yaksh, 1994; Sorkin et al, 2008). The motor side effects clearly show that the test article had biological activity and are consistent with the distribution of P/Q-type (α1A) calcium channel subunits in the ventral horn motor neurons (Kim et al, 2001; Murakami et al, 2004).…”

Spinal p38 mitogen‐activated protein kinase mediates allodynia induced by first‐degree burn in the rat

“…Unlike NMDA dependent models of pain, first‐degree burn‐induced tactile allodynia is not dependent on CamKinase IIα (Jones and Sorkin, 2005) or activation of either cyclooxygenase or nitric oxide synthase (Sorkin et al, 2008). Thus, other second messengers and signal transduction cascades may be activated after activation of AMPA receptors.…”