The threshold for the depressive effect of intrathecal morphine on the spinal nociceptive flexor reflex is increased during autotomy after sciatic nerve section in rats

Abstract

The effect of intrathecal (i.t.) morphine on the spinal nociceptive flexor reflex in doses ranging between 10 ng and 10 μg was studied in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves or in rats in which the sciatic nerve had been unilaterally sectioned. In rats with intact nerves the initial effect of i.t. morphine on the flexor reflex was a brief facilitation followed by depression. The threshold dose of morphine for reflex depression was 100 ng. In animals which did not develop autotomy after nerve section or in which autotomy had ceased for several days prior to the acute experiments i.t. morphine had a similar depressive effect on the flexor reflex as in animals with intact nerves. However, in rats which were autotomizing at the time of the acute experiment, the threshold dose of the depressive effect of morphine was increased 3–5 fold. With higher doses of morphine (1–3 μg), similar depression of the reflex was found in all groups. The present results revealed a decreased sensitivity of spinal reflex mechanisms to low, but not high, doses of morphine after sciatic nerve section accompanied by autotomy. Nerve section per se did not alter opioid sensitivity. Thus, decreased effectiveness of morphine in this model for neuropathic pain may be partially due to a desensitization to the analgesic action of opioids in the spinal cord. Since after sciatic nerve section there is a differential sensitivity to the antinociceptive effect of i.t. morphine between autotomizing and non-autotomizing rats, it is further suggested that autotomy after peripheral nerve section in rats is a useful model for the study of neuropathic pain.