Evaluación del efecto antinociceptivo y mecanismo de acción del ácido docosahexaenoico (DHA) en un modelo murino de dolor neuropático

Abstract

Diabetic neuropathy is not an entity of the disease, but a series of diseases or injuries with a set of symptoms and signs, where the understanding of the pathophysiology is evolving. The management of neuropathic pain can be challenging and the drugs used in the treatment of neuropathic pain as neuromodulators (gabapentin or pregabalin) are limited by the presence of significant adverse effects. Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid that has shown an antinociceptive effect in multiple pain models, such as inflammatory and neuropathic pain due to chronic constriction injury in rats; however, its mechanism of action is still not well understood. Reports suggest that DHA activates opioid signaling, but there is no information on this in a neuropathic pain model. As a result, the objectives of this study were (1) to determine the antihyperalgesic and antiallodynic effect of the peripheral administration of DHA, (2) to evaluate the participation of opioid receptors in the antihyperalgesic effect of DHA on neuropathic pain induced by streptozotocin and (3) evaluate the decrease in spinal cord expression of TNF-α and FCN-β with the administration of DHA. Female Wistar female rats were injected with streptozotocin (50 mg/kg, i.p.) to induce hyperglycemia. The formalin, Hargreaves and von Frey filament tests were used to evaluate the nociceptive activity. The intraplantar administration of DHA (100-1000 μg/paw) or gabapentin (562-1778 μg/paw) reduced the formalin-induced hyperalgesia in diabetic rats, in a dose-dependent manner. In addition, DHA (562 μg/paw) and gabapentin (1000 μg/paw) reduced thermal hyperalgesia and allodynia. Local peripheral administration of naloxone (non-selective opioid receptor antagonist, 100 μg / paw), naltrindol (selective receptor antagonist, 1 μg/paw) and CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, μ receptor antagonist: 20 μg/paw) prevented formalin-induced hyperalgesia in diabetic rats, but not by NGTI (guanidinonaltrindole, κ receptor antagonist, 1 μg/paw). It is suggested that peripheral DHA shows an antihyperalgesic effect in neuropathic pain in the rat. In addition, the receptors δ and μ are involved in the peripheral antihyperalgesic effect of DHA in diabetic rats