کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2531216 1558914 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Intrathecal administration of nociceptin/orphanin FQ receptor agonists in rats: A strategy to relieve chemotherapy-induced neuropathic hypersensitivity
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Intrathecal administration of nociceptin/orphanin FQ receptor agonists in rats: A strategy to relieve chemotherapy-induced neuropathic hypersensitivity
چکیده انگلیسی

Oxaliplatin and paclitaxel are considered central components in the treatment of colorectal and breast cancer, respectively. The development of neuropathy during chronic treatment represents the major dose-limiting side effect that leads to discontinuation or interruption of therapies. The management of neuropathy is a challenge to individuate innovative therapeutic strategies based on new targets and correct routes of administration. We evaluated the hypersensitivity reliever effect of different opioid receptor agonists in rat models of oxaliplatin and paclitaxel-induced neuropathy. Compounds were spinally infused by intrathecal catheter. In oxaliplatin-treated rats, 0.3 nmol morphine induced the reversion of the mechanical hypersensitivity (Paw-pressure test), nociceptin/orphanin FQ (N/OFQ; 0.3–3 nmol) significantly increased the pain threshold without reaching the values of the control animals. The N/OFQ peptide (NOP) receptor full agonist UFP-112 reverted pain threshold alterations at lower dosage (0.1 nmol) vs morphine and N/OFQ, the partial agonist UFP-113 (0.1–1 nmol) was similar to N/OFQ. The higher efficacy of morphine vs N/OFQ was highlighted also in paclitaxel-treated rats. The mechanical hypersensitivity was fully reverted by 0.1 nmol UFP-112 and UFP-113. In conclusion, intrathecal μ opioid peptide (MOP) and NOP receptor agonists relieved chemotherapy-induced neuropathic pain. The synthetic peptides showed valuable potency and efficacy suggesting the NOP system as an exploitable target.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 766, 5 November 2015, Pages 155–162
نویسندگان
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