Mh. Ossipov et al., INHIBITION BY SPINAL MORPHINE OF THE TAIL-FLICK RESPONSE IS ATTENUATED IN RATS WITH NERVE LIGATION INJURY, Neuroscience letters, 199(2), 1995, pp. 83-86
Nerve ligation injury in rats produces increased sensitivity and exagg
erated responses to nociceptive stimuli (hyperalgesia) as well as noci
ceptive responses to normally innocuous stimuli (allodynia) analogous
to clinical conditions of neuropathic pain. However, the effect of ner
ve injury on acute nociception has not been extensively studied. Nerve
ligation injury was produced by unilateral ligation of the L5 and L6
spinal roots of the sciatic nerve of male Sprague-Dawley rats. Intrath
ecal (i.th.) catheters were inserted for spinal drug administration. R
esponse to acute nociception was measured by determining the latency t
o a rapid flick of the tail (TF) after immersion into a 55 degrees C w
ater bath before (control) and after i.th. morphine administration. No
change in baseline response to the nociceptive stimulus was observed
in either sham-operated or nerve-injured rats. In sham-operated rats,
morphine produced dose-dependent antinociception with a 97 +/- 2.3% ma
ximal possible effect (MPE) at a 60 mu g dose; in these controls A(50)
(95% CL) was 22 mu g (17-30 mu g). Morphine administered to rats with
nerve injury also produced dose-dependent increase in TF latency, but
an MPE of only 60 +/- 17% was obtained at 100 mu g; higher doses elic
ited signs of behavioral toxicity. While it was not possible to produc
e a proper dose-response curve with i.th. morphine in animals with ner
ve injury, an estimation of the A(50) showed approximately a four-fold
loss of potency compared to sham-operated controls. Antinociception w
as readily reversed by naloxone (5 mg/kg, i.p.) in both groups. These
data indicate that nerve ligation injury reduces the potency and effic
acy of i.th. morphine. While the reasons for this loss of morphine act
ivity in nerve injured animals are unknown, it is possible to speculat
e that (a) degeneration of primary afferents subsequent to nerve ligat
ion injury might result in a loss of presynaptic opioid (mu?) receptor
s in the dorsal horn, thereby reducing the antinociceptive activity of
morphine at the spinal level; (b) changes in the efficiency of post-r
eceptor transduction may occur following nerve injury which can reduce
opioid efficacy; (c) changes in levels of spinal neurotransmitters (e
.g., cholecystokinin) may act to diminish opioid action; or (d) sustai
ned afferent input from the site of the injury may be important in lim
iting the activity of opioids.