Tolerance to the antinociceptive effect of morphine in spinally transected rats.

Examined the effect of a spinal transection (ST) on morphine (MOR)-induced tolerance in rats with the tail withdrawal reflex (tail flick; TF), elicited by noxious thermal stimulation. Intact Ss became tolerant to sc MOR injections if they were tested on the TF after each injection. MOR administration alone did not produce tolerance; TF tests alone did, although not always to a significant extent. However, when MOR only, TF tests only, or both were administered prior to ST (acute spinal Ss), all groups were tolerant when tested 1 day after spinalization. When the same treatments were administered to Ss 3 wks after ST (chronic spinal Ss), neither MOR nor TF tests alone produced tolerance. Chronic spinal Ss became tolerant only if they were tested after each injection. Results suggest that tolerance develops at the spinal cord as a result of either chronic opiate exposure or performance of the nociceptive response, but in intact Ss, tolerance is inhibited or suppressed by a supraspinal action of MOR. Results also suggest that such tolerance is mediated by descending input or that ST produced intrinsic changes in the spinal cord that preclude the development of tolerance induced only by opiate or behavioral stimulation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of morphine-induced effects on thermal nociception, mechanoreception, and hind limb flexion in chronic spinal rats.

The effect of systemic morphine on 3 behaviors in the same group of chronic spinal rats was examined: the tail-flick (TF) reflex to a noxious thermal stimulus, limb withdrawal (LW) to mechanoreceptor (von Frey hair) stimulation, and hind limb flexion (flexor reflex [FR]) elicited by innocuous electrical stimulation of the toes. Compared with intact rats, the potency of morphine on both the TF and the hind paw (but not the forepaw) LW response was significantly reduced. Morphine's effect on the FR depended on the dose. The lowest dose (1.0 mg/kg) produced no change, 4.0 mg/kg decreased response magnitude by approximately 50% (indicating an antispastic effect), and 8.0 mg/kg increased flexor magnitude by 100%. The concurrent TF and FR assays revealed a dissociation of morphine's effects in that the highest dose (8.0 mg/kg) significantly inhibited the nociceptive TF response but facilitated the FR in the same chronic spinal rats. This outcome may be relevant to the phenomenon of "opioid-related myoclonus" recently described in cancer patients, which "was highly associated with nerve dysfunction due to spinal cord lesions" (S. Mercadante, 1998, p. 6). (PsycINFO Database Record (c) 2010 APA, all rights reserved)