1. Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury
- Author
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Aceves, M, Mathai, B B, and Hook, M A
- Abstract
Objective:The current study aimed to evaluate the contribution(s) of specific opioid receptor systems to the analgesic and detrimental effects of morphine, observed after spinal cord injury in prior studies.Study design:We used specific opioid receptor agonists to assess the effects of μ- (DAMGO), δ- (DPDPE) and κ- (GR89696) opioid receptor activation on locomotor (Basso, Beattie and Bresnahan scale, tapered beam and ladder tests) and sensory (girdle, tactile and tail-flick tests) recovery in a rodent contusion model (T12). We also tested the contribution of non-classic opioid binding using [+]- morphine.Methods:First, a dose–response curve for analgesic efficacy was generated for each opioid agonist. Baseline locomotor and sensory reactivity was assessed 24 h after injury. Subjects were then treated with an intrathecal dose of a specific agonist and re-tested after 30 min. To evaluate the effects on recovery, subjects were treated with a single dose of an agonist and both locomotor and sensory function were monitored for 21 days.Results:All agonists for the classic opioid receptors, but not the [+]- morphine enantiomer, produced antinociception at a concentration equivalent to a dose of morphine previously shown to produce strong analgesic effects (0.32 μmol). DAMGO and [+]- morphine did not affect long-term recovery. GR89696, however, significantly undermined the recovery of locomotor function at all doses tested.Conclusions:On the basis of these data, we hypothesize that the analgesic efficacy of morphine is primarily mediated by binding to the classic μ-opioid receptor. Conversely, the adverse effects of morphine may be linked to activation of the κ-opioid receptor. Ultimately, elucidating the molecular mechanisms underlying the effects of morphine is imperative to develop safe and effective pharmacological interventions in a clinical setting.Setting:USA.Sponsorship:Grant DA31197 to MA Hook and the NIDA Drug Supply Program.
- Published
- 2016
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