Pharmacology of spinal glutamatergic receptors in post-thermal injury-evoked tactile allodynia and thermal hyperalgesia.
BACKGROUND
After a focal thermal injury to the heel of a rat, thermal hyperalgesia appears at the injury site (primary thermal hyperalgesia), and tactile allodynia appears at the off-injury site (secondary tactile allodynia). The pharmacology of spinal glutamatergic receptors in the initiation and maintenance of secondary tactile allodynia was examined.


METHODS
In rats prepared with chronic intrathecal catheters, the heel of one hind paw was exposed to a 52 degrees C surface for 45 s, resulting in a local erythema without blistering. Intrathecal N-methyl-d-aspartate (NMDA) receptor antagonists (MK-801, AP5) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-kainate (AMPA-KA) receptor antagonists (CNQX, NBQX, NS257, etc.) were administered either before (pretreatment) or after (posttreatment) the induction of the injury. Tactile withdrawal thresholds and thermal paw withdrawal latencies were assessed.


RESULTS
Pretreatment and posttreatment with AMPA-KA antagonists produced a dose-dependent blockade of secondary tactile allodynia. However, NMDA antagonists, in doses that effectively block other models of facilitated states, showed little or no effect. Primary thermal hyperalgesia was blocked only by high-dose AMPA-KA antagonists.


CONCLUSIONS
Spinal AMPA-KA receptors play a major role in the initiation of secondary tactile allodynia induced by focal thermal injury. In contrast, spinal NMDA receptors play only a minimal role.
Nozaki-Taguchi
Natsuko
N
Department of Anesthesiology, University of California-San Diego, La Jolla, California 92093-0818, USA.
Yaksh
Tony L
TL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002056:Burns / Q000150:complications / Q000503:physiopathology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005528:Foot / Q000473:pathology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017470:Receptors, Glutamate / Q000187:drug effects*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate