Excitatory amino acid release in the spinal cord caused by plantar incision in the rat

There is extensive evidence that spinal excitatory amino acids (EAAs) like glutamate (Glu) and aspartate (Asp) are important in the processing of nociceptive behaviors caused by incisions. To better understand EAA-induced dorsal horn sensitization caused by surgery, we examined the time course and extent of spinal amino acid (AA) release during and after a plantar incision utilizing in vivo microdialysis. We also examined the role of primary afferent input and axonal conduction by measuring spinal EAAs in rats after hindpaw denervation and in rats treated with spinal tetrodotoxin (TTX). In halothane-anesthetized rats, a microdialysis filament (200 mum diameter, 45,000 MW cut off, Hospal AN69) was passed transversely through the deep dorsal horn of the spinal cord (L4-L6). After 18-24 h, the dialysis filament was perfused with artificial cerebrospinal fluid (ACSF), dialysate samples collected and analyzed for AAs (Glu, Asp, asparagine, glutamine, serine, and glycine). Rats underwent anesthetic induction with halothane followed by a plantar incision (n = 8) or sham operation (it = 8). AAs were also measured in incised rats that underwent hindpaw denervation (n = 4), in rats that had the filament placed outside the L4-L6 spinal segments (n = 7), in rats with a microdialysis catheter placed in the ventral horn at L4-L6 (n = 7) and in rats treated with spinally administered TTX (it = 5). AAs were measured during recovery from anesthesia and for the next 8 It. In the sham-operated group, Asp and Glu did not change throughout the experiment. In rats undergoing plantar incision, Asp and Glu increased from 10 to 30 min after incision to 200 +/- 30 and 138 +/- 12 percentage of control, respectively. The EAAs returned to baseline by I h after incision. For the other AAs, only serine and asparagine increased after incision. No increase in AA release by incision was observed after hindpaw denervation, TTX treatment or placement of the filament outside the L4-L6 segments. In rats with a filament implanted in the ventral horn (L4-L6), EAAs increased during halothane induction and sham preparation. Thus, the EAA release required an intact afferent nerve barrage and segmental excitatory nerve transmission. The incision-induced nociceptive afferent barrage increased the release of Glu and Asp in the lumbar dorsal horn for 45 min. The concentrations of AAs returned to baseline by 1 It. The percentage increase is in some cases less and for a shorter period of time compared to other models of persistent pain, perhaps because the incision injury is less severe compared to others models. This profile of EAA release further explains why models of inflammation and chemical irritation do not translate well to human postoperative pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.