کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5814794 1556643 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Potentiation of morphine-induced mechanical antinociception by σ1 receptor inhibition: Role of peripheral σ1 receptors
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Potentiation of morphine-induced mechanical antinociception by σ1 receptor inhibition: Role of peripheral σ1 receptors
چکیده انگلیسی


- σ1 inhibition does not affect mechanical nociception (in the absence of morphine).
- σ1 receptor inhibition potentiates morphine-induced mechanical antinociception.
- Peripheral σ1 receptors tonically limit peripheral morphine antinociception.
- Acute morphine-induced side effects are unaltered in σ1 knockout mice.

We studied the modulation of morphine-induced mechanical antinociception and side effects by σ1 receptor inhibition. Both wild-type (WT) and σ1 receptor knockout (σ1-KO) mice showed similar responses to paw pressure (100-600 g). The systemic (subcutaneous) or local (intraplantar) administration of σ1 antagonists (BD-1063, BD-1047, NE-100 and S1RA) was devoid of antinociceptive effects in WT mice. However, σ1-KO mice exhibited an enhanced mechanical antinociception in response to systemic morphine (1-16 mg/kg). Similarly, systemic treatment of WT mice with σ1 antagonists markedly potentiated morphine-induced antinociception, and its effects were reversed by the selective σ1 agonist PRE-084. Although the local administration of morphine (50-200 μg) was devoid of antinociceptive effects in WT mice, it induced dose-dependent antinociception in σ1-KO mice. This effect was limited to the injected paw. Enhancement of peripheral morphine antinociception was replicated in WT mice locally co-administered with σ1 antagonists and the opioid. None of the σ1 antagonists tested enhanced morphine-antinociception in σ1-KO mice, confirming a σ1-mediated action. Morphine-induced side-effects (hyperlocomotion and inhibition of gastrointestinal transit) were unaltered in σ1-KO mice. These results cannot be explained by a direct interaction of σ1 ligands with μ-opioid receptors or adaptive changes of μ-receptors in σ1-KO mice, given that [3H]DAMGO binding in forebrain, spinal cord, and hind-paw skin membranes was unaltered in mutant mice, and none of the σ1 drugs tested bound to μ-opioid receptors. These results show that σ1 receptor inhibition potentiates morphine-induced mechanical analgesia but not its acute side effects, and that this enhanced analgesia can be induced at peripheral level.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 70, July 2013, Pages 348-358
نویسندگان
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