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Background and Objective: The melanocortin-4 (MC4) receptor has been evaluated as a possible new therapeutic for neuropathic pain treatment. The purpose of this review article was to review and evaluate all recent in vivo studies on the effect of the MC4 receptor antagonist HS014 on rat hypersensitivity caused by neuropathic pain.  Methods: An electronic search was carried out using Scopus, Web of Science, PubMed, and Google Scholar. The following inclusion criteria were used: rat models of neuropathic pain-induced hypersensitivity, with investigated effects of the selective antagonist HS014. The included duration of the search was within the last ten years. Data regarding HS014, neuropathic pain model, post-treatment administration time and dose (days post-injury), behavior assessment assays, treatment frequency, and route of delivery were collected and subjected descriptively as complementary data in this narrative review.  Results: This narrative review included four papers that fulfilled the eligibility criteria. The findings demonstrate that as compared to vehicle-treated rats, administration of the MC4 receptor antagonist HS014 remarkably raised paw withdrawal threshold (PWT) in three studies and heat withdrawal latency in four studies among rat models subjected to neuropathic pain.  Conclusions: In rat neuropathic pain models, the MC4 receptor antagonist HS014 is helpful in reducing hypersensitivity. However, further studies are needed to determine the ideal treatment dosage and timing. In addition, further investigations are required for the role of this selective receptor antagonist (HS014) and compared with other types of MC4 receptors in neuropathic pain in humans.

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Influence of Selective Melanocortin-4 Receptor Antagonist HS014 on Hypersensitivity After Nervous System Injuries in a Model of Rat Neuropathic Pain: A Narrative Review of the Literature