Evaluation of the Antinociceptive Effect of Sesamin: Role of 5HT1A Serotonergic Receptors.

Abstract

Background/Objectives: Sesame (Sesamum indicum L.) is used in folk medicine to treat painful disorders. Sesamin is the main lignan found in this plant; however, its antinociceptive potential has scarcely been studied. The aim was to investigate the antinociceptive effect of sesamin on inflammatory and neuropathic pain models, as well as the possible mechanism of action through which sesamin mediates its own antinociceptive effect. Methods: Formalin and carrageenan animal models were used to assess inflammatory pain, whereas an L5/L6-spinal-nerve-ligated rat model was employed to evaluate neuropathic pain. Results: Oral sesamin significantly reduced carrageenan-induced hyperalgesia and inflammation, formalin-induced nociception, and L5/L6-spinal-nerve-ligation-induced allodynia. Sesamin was more effective than diclofenac in the inflammatory pain models, but it was less effective than pregabalin in the neuropathic pain model. The antinociceptive effect of sesamin, in the formalin test, was prevented by the intraperitoneal administration of methiothepin (5-HT_1/5 antagonist), but not by naltrexone (an opioid antagonist) or L-NAME (an NOS inhibitor). In addition, WAY-100635 (5-HT_1A antagonist), but not SB-224289 (5-HT_1B antagonist), BRL-15542 (5-HT_1D antagonist), and SB-699551 (5-HT_5A antagonist), impeded sesamin-induced antinociception. Conclusions: This study's results support the use of sesamin to treat inflammatory pain disorders and suggest that 5-HT_1A receptors influence the antinociceptive effect of this drug.