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Morphine and dextrorphan lose antinociceptive activity but exhibit an antispastic action in chronic spinal rats
C Advokat1, H Mosser, K Hutchinson
1Department of Psychology, Louisiana State University, Baton Rouge 70803, USA.
Abstract:
Within 3-4 weeks after spinal transection, morphine-induced antinociception, assessed with the tail flick reflex in rats, is profoundly reduced. The cause of this decrement is unknown. The present studies were conducted to determine whether this phenomenon reflects a general loss in opiate activity or a selective decline in opiate antinociception. This was accomplished by assessing the effect of morphine on two different responses, the tail flick reflex and the hindlimb spasticity that develops in chronic spinal rats. Because excitatory amino acid antagonists are also antinociceptive in acute spinal rats, the effect of one such drug, dextrorphan, on these two behaviors was also evaluated in chronic spinal animals. The antinociceptive and antispastic effect of subcutaneous (6 mg/kg) and intrathecal (5 micrograms) morphine injections were assessed in intact and chronic (21-28 days) spinal rats, whereas the effect of subcutaneous (25 and 40 mg/kg) and intrathecal (350 micrograms) dextrorphan was assessed in acute (1 day) and chronic spinal rats. The antinociceptive effect of both drugs was significantly reduced in chronic spinal animals, relative to saline controls. However, each drug treatment produced a significant antispastic effect in the same animals, indicating a selective decline in opiate action. This outcome also suggests that excitatory amino acid antagonists may be useful as adjunct antispastic agents.
Insights
Spinal transection in rats reduces morphine
Area of Science:
- Neuroscience
- Pharmacology
- Spinal Cord Injury Research
Background:
- Spinal cord transection in rats leads to a significant reduction in morphine's pain-relieving effects (antinociception) within 3-4 weeks.
- The underlying cause of this diminished opioid efficacy remains unclear, prompting investigation into whether it signifies a general decrease in opioid activity or a specific loss of antinociceptive function.
Purpose of the Study:
- To investigate the selective decline of morphine's antinociceptive effects after spinal transection.
- To compare the effects of morphine on pain (tail flick reflex) versus spasticity in chronic spinal rats.
- To evaluate the efficacy of dextrorphan, an excitatory amino acid antagonist, on antinociception and antispasticity in chronic spinal models.
Main Methods:
- Assessed the antinociceptive and antispastic effects of morphine and dextrorphan in intact, acute spinal, and chronic spinal rats (21-28 days post-transection).
- Administered drugs via subcutaneous and intrathecal routes to evaluate dose-dependent effects.
- Utilized the tail flick reflex to measure antinociception and observed hindlimb spasticity for antispastic effects.
Main Results:
- Both morphine and dextrorphan showed significantly reduced antinociceptive effects in chronic spinal rats compared to saline controls.
- Despite reduced pain relief, both morphine and dextrorphan demonstrated significant antispastic effects in the same chronic spinal rats.
- This indicates a selective loss of antinociceptive action rather than a general decrease in opioid or antagonist efficacy.
Conclusions:
- Opioid antinociception is selectively impaired following spinal transection, while antispastic effects may be preserved.
- Excitatory amino acid antagonists, like dextrorphan, show potential as adjunctive therapies for managing spasticity after spinal cord injury.
- These findings highlight a dissociation between antinociceptive and antispastic mechanisms in the chronic spinal state.