We investigated the effects of acute and of chronic morphine treatment on T
-lymphocyte function and natural killer (NK) cell activity in rats receivin
g chronic constriction injury (CCI) of the sciatic nerve. T-Lymphocyte func
tion was evaluated based on concanavalin-A (ConA)- and phytohemagglutinin (
PHA)-induced splenocyte proliferation. The effects of morphine on thermal h
yperalgesia were also assessed by measuring paw withdrawal latency (PWL) in
rats. All of the rats that received CCI developed thermal hyperalgesia whi
le sham-operated rats did not. Thermal hyperalgesia was dose-dependently re
versed after acute (single injection) and after chronic (daily injection fo
r 7 days) administration of morphine but persisted in saline-treated CCI ra
ts. There was no significant difference between sham and saline-treated CCI
groups in splenocyte proliferation and NK cell activity. NK cell activity
and splenocyte proliferation induced by ConA and PHA were significantly sup
pressed by acute morphine treatment in a dose-dependent manner. The reversa
l of the thermal hyperalgesia persisted throughout the period of chronic mo
rphine treatment. No tolerance to the suppression of NK cell activity and s
plenocyte proliferation was observed after chronic morphine treatment. Thes
e data suggest that both acute and chronic morphine treatment can cause a d
ose-dependent reversal of thermal hyperalgesia and inhibition of NK cell ac
tivity and splenocyte proliferation in rats with sciatic CCI, without conco
mitant development of tolerance. Opioid therapy for chronic neuropathic pai
n should be used cautiously, especially in immune-compromised cases. (C) 20
00 International Association for the Study of Pain. Published by Elsevier S
cience B.V. All rights reserved.