L. Jasmin et al., THE COLD PLATE AS A TEST OF NOCICEPTIVE BEHAVIORS - DESCRIPTION AND APPLICATION TO THE STUDY OF CHRONIC NEUROPATHIC AND INFLAMMATORY PAIN MODELS, Pain, 75(2-3), 1998, pp. 367-382
A cold plate apparatus was designed to test the responses of unrestrai
ned rats to low temperature stimulation of the plantar aspect of the p
aw. At plate temperatures of 10 degrees C and 5 degrees C, rats with e
ither chronic constriction injury (CCI) of the sciatic nerve or comple
te Freund's adjuvant (CFA) induced inflammation of the hindpaw display
ed a stereotyped behavior. Brisk lifts of the treated hindpaw were rec
orded, while no evidence of other nociceptive behaviors could be disce
rned. The most consistent responses were obtained with a plate tempera
ture of 5 degrees C in three 5-min testing periods, separated by 10-mi
n intervals during which the animals were returned to a normal environ
ment. Concomitantly to cold testing, the rats were evaluated for their
response to heat (plantar test) and mechanical (von Frey hairs) stimu
li. In both injury models, while responses to heat stimuli had normali
zed at 60 days post-injury, a clear lateralization of responses to col
d was observed throughout the entire study period. Systemic lidocaine,
clonidine, and morphine suppressed responses to cold in a dose-relate
d fashion. At doses that did not affect motor or sensory behavior, bot
h lidocaine and its quaternary derivative QX-314 similarly reduced paw
lifts, suggesting that cold hyperalgesia is in part due to peripheral
altered nociceptive processing. Clonidine was more potent in CCI then
in CFA rats in reducing the response to cold. Paradoxically, clonidin
e increased the withdrawal latencies to heat in the CCI hindpaw at 40
days and thereafter, at a time when both hindpaws had the same withdra
wal latencies in control animals. Morphine was also more potent on CCI
than CFA cold responses, indicating that, chronically, CFA-induced hy
peralgesia might be opiate resistant. Evidence for tonic endogenous in
hibition of cold hyperalgesia was obtained for CFA rats, when systemic
naltrexone significantly increased the number of paw lifts; this was
not found in rats with CCI. At 60 days, neither morphine nor naltrexon
e affected cold-induced paw lifting in CFA rats, suggesting that the n
euronal circuit mediating cold hyperalgesia in these animals had becom
e opiate insensitive. In conclusion; the cold plate was found to be a
reliable method for detecting abnormal nociceptive behavior even at lo
ng intervals after nerve or inflammatory injuries, when responses to o
ther nociceptive stimuli have returned to near normal. The results of
pharmacological studies suggest that cold hyperalgesia is in part a co
nsequence of altered sensory processing in the periphery, and that it
can be independently modulated by opiate and adrenergic systems. (C) 1
998 International Association for the Study of Pain. Published by Else
vier Science B.V.