Dissociation between morphine-induced spinal gliosis and analgesic tolerance by ultra-low-dose α2-adrenergic and cannabinoid CB1-receptor antagonists
| Autor: | Mary C. Olmstead, Catherine M. Cahill, David Wiercigroch, Patrick Grenier |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cannabinoid receptor medicine.medical_treatment Pharmacology ultra-low dose Rats Sprague-Dawley Norepinephrine chemistry.chemical_compound 0302 clinical medicine Receptor Cannabinoid CB1 Rimonabant Gliosis atipamezole Injections Spinal Pain Measurement Analgesics tolerance Morphine alpha(2)-adrenergic receptor Imidazoles Atipamezole analgesia Pharmacology and Pharmaceutical Sciences Drug Tolerance Adrenergic alpha-2 Receptor Antagonists CB1 Analgesics Opioid Psychiatry and Mental health efaroxan rimonabant Drug Neuroglia Receptor medicine.drug Spinal Analgesic Opioid Injections Dose-Response Relationship 03 medical and health sciences medicine Animals Cannabinoid Cannabinoid Receptor Antagonists Benzofurans Neurology & Neurosurgery Dose-Response Relationship Drug Cannabinoids business.industry Antagonist Efaroxan Spine Rats 030104 developmental biology chemistry Sprague-Dawley business 030217 neurology & neurosurgery |
| Zdroj: | Behavioural pharmacology, vol 29, iss 2 and 3-Spec Issue |
| ISSN: | 0955-8810 |
| Popis: | Long-term use of opioid analgesics is limited by tolerance development and undesirable adverse effects. Paradoxically, spinal administration of ultra-low-dose (ULD) G-protein-coupled receptor antagonists attenuates analgesic tolerance. Here, we determined whether systemic ULD α2-adrenergic receptor (AR) antagonists attenuate the development of morphine tolerance, whether these effects extend to the cannabinoid (CB1) receptor system, and if behavioral effects are reflected in changes in opioid-induced spinal gliosis. Male rats were treated daily with morphine (5 mg/kg) alone or in combination with ULD α2-AR (atipamezole or efaroxan; 17 ng/kg) or CB1 (rimonabant; 5 ng/kg) antagonists; control groups received ULD injections only. Thermal tail flick latencies were assessed across 7 days, before and 30 min after the injection. On day 8, spinal cords were isolated, and changes in spinal gliosis were assessed through fluorescent immunohistochemistry. Both ULD α2-AR antagonists attenuated morphine tolerance, whereas the ULD CB1 antagonist did not. In contrast, both ULD atipamezole and ULD rimonabant attenuated morphine-induced microglial reactivity and astrogliosis in deep and superficial spinal dorsal horn. So, although paradoxical effects of ULD antagonists are common to several G-protein-coupled receptor systems, these may not involve similar mechanisms. Spinal glia alone may not be the main mechanism through which tolerance is modulated. |
| Databáze: | OpenAIRE |
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