British Journal of Anaesthesia, Vol 80, Issue 3 348-353, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia
H. Buerkle, M. Marsala and T. L. Yaksh
Injection of formalin into the hind paw of the rat evokes a biphasic
nociceptive behavioural response, which is considered to be an animal model
of postoperative pain in humans. The initial response (phase 1) is caused
by activation of peripheral nociceptors and is followed by a second phase
attributed to ongoing activity in primary afferents and increased
sensitivity of dorsal horn neurones. The latter effect is thought to result
from glutamate-mediated N-methyl-D-aspartate receptor activation. In
studies to date it has been difficult to discriminate mechanisms underlying
phase 1 and phase 2 events because of the long- lasting half-times of
intrathecally administered opioids. To further understanding of the opioid
pharmacology of the two different phases of the formalin test, we have
studied behavioural activity and spinal glutamate release after intrathecal
administration of remifentanil, a new short-lasting mu opioid. Intrathecal
remifentanil 3 micrograms microliter-1 min-1 delivered during phase 1
inhibited behavioural response during phase 1 (100%), but did not abolish
subsequent phase 2 behavioural activity completely (67 (12) %). Intrathecal
remifentanil administered separately in phase 1 and phase 2 revealed a
similar ED50 (0.2 microgram microliter-1 min-1) for inhibition of the
behavioural responses. In vivo, spinal microdialysis showed incomplete
reduction in glutamate concentrations in response to intrathecal
remifentanil administration; this in turn inhibited phase 1 behavioural
responses. Therefore we contend that supramaximal doses of intrathecal
remifentanil sufficient to inhibit phase 1 activity still permitted
sufficient glutamate release to allow spinal facilitation. Incomplete
suppression of spinal excitatory neurotransmitter release by intrathecal
opioids is consistent with spinal wind-up that is triggered during phase 1
and results in phase 2 afferent drive. This might reflect one of the
mechanisms underlying post-operative pain.
LABORATORY INVESTIGATIONS
Effect of continuous spinal remifentanil infusion on behaviour and spinal glutamate release evoked by subcutaneous formalin in the rat
Department of Anesthesiology, University of California, San Diego, CA, USA
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. L. Yaksh, G. Ozaki, D. McCumber, M. Rathbun, C. Svensson, S. Malkmus, and M. C. Yaksh An automated flinch detecting system for use in the formalin nociceptive bioassay J Appl Physiol, June 1, 2001; 90(6): 2386 - 2402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Yaksh, X.-Y. Hua, I. Kalcheva, N. Nozaki-Taguchi, and M. Marsala The spinal biology in humans and animals of pain states generated by persistent small afferent input PNAS, July 6, 1999; 96(14): 7680 - 7686. [Abstract] [Full Text] [PDF]
|
|