Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury
| العنوان: | Evaluation of the effects of specific opioid receptor agonists in a rodent model of spinal cord injury |
|---|---|
| المؤلفون: | Miriam Aceves, Babetta B. Mathai, Michelle A. Hook |
| المصدر: | Spinal cord |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Pyrrolidines, Neurology, medicine.drug_class, Severity of Illness Index, Article, Piperazines, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Opioid receptor, medicine, Animals, locomotor recovery, pain, Spinal cord injury, Spinal Cord Injuries, Pain Measurement, Analysis of Variance, Dose-Response Relationship, Drug, Morphine, business.industry, Body Weight, analgesia, Rodent model, Recovery of Function, General Medicine, Enkephalin, Ala(2)-MePhe(4)-Gly(5), medicine.disease, spinal cord injury, Rats, 3. Good health, Analgesics, Opioid, Disease Models, Animal, 030104 developmental biology, Anesthesia, opioid, Neurology (clinical), Enkephalin, D-Penicillamine (2,5), Paraplegia, business, Locomotion, 030217 neurology & neurosurgery |
| الوصف: | 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.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.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.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.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.USA.Grant DA31197 to MA Hook and the NIDA Drug Supply Program. |
| تدمد: | 1476-5624 1362-4393 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4919f4d07586bd61c235bbed4e98fee https://doi.org/10.1038/sc.2016.28 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b4919f4d07586bd61c235bbed4e98fee |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14765624 13624393 |
|---|