Laboratório de Pesquisa em Farmacologia Bioquímica, LaFarBio, Programa de Pós-Graduação em Bioquímica e Bioprospecção, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, Pelotas, RS 96010-900, Brazil.
Laboratório de Pesquisa em Farmacologia Bioquímica, LaFarBio, Programa de Pós-Graduação em Bioquímica e Bioprospecção, CCQFA, Universidade Federal de Pelotas, UFPel, P.O. Box 354, Pelotas, RS 96010-900, Brazil.
Brain Res Bull. 2022 Sep;187:11-23. doi: 10.1016/j.brainresbull.2022.06.005. Epub 2022 Jun 24.
Fibromyalgia results from a complex interplay of biochemical and neurobiological elements mediated sensitization of nociceptive pathways. Despite the symptoms of fibromyalgia negatively affect the quality of life of patients, the pathophysiology of this disease remains inconclusive, which difficult the development of an appropriate treatment. The present study investigated the involvement of the serotonergic receptors, the N-methyl-D-aspartate (NMDA)/ nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway and the oxidative stress in an animal model of fibromyalgia induced by intermittent cold stress (ICS), considering the specificities of male and female Swiss mice. The ICS exposure increased mechanical and thermal sensitivities, and decreased muscle strength in mice of both sexes. Female mice exhibited a longer-lasting mechanical sensitivity than male mice exposed to ICS along with an enhancement of the Na, K-ATPase activity in the spinal cord and cerebral cortex. Conversely, an inhibition in the Na, K-ATPase and glutathione peroxidase activities accompanied by an increase in the reactive species levels in the cerebral cortex of male mice were observed. The treatment with different serotonergic antagonists (pindolol, ketanserin and ondasetron) reversed the mechanical sensitivity in mice of both sexes, after the ICS exposure. The administration of MK-801, L-arginine and methylene blue also blocked the mechanical sensitivity in female mice exposed to ICS. Except L-arginine, MK-801 and methylene blue also attenuated this nociceptive signal in male mice, after ICS exposure. In conclusion, the modulation of serotonergic receptors, the NMDA/NO/cGMP pathway, and the oxidative stress seems contribute to nociceptive behaviors induced by ICS exposure sex-dependent.
纤维肌痛症是由生化和神经生物学因素的复杂相互作用引起的，其介导了伤害感受途径的敏化。尽管纤维肌痛症的症状会负面地影响患者的生活质量，但这种疾病的病理生理学仍然不确定，这使得合适的治疗方法难以开发。本研究通过间歇性冷应激（ICS），在雄性和雌性瑞士小鼠的动物模型中，调查了 5-羟色胺能受体、N-甲基-D-天冬氨酸（NMDA）/一氧化氮（NO）/环鸟苷单磷酸（cGMP）途径和氧化应激的参与情况，考虑到两性的特异性。ICS 暴露会增加机械和热敏感性，并降低雌雄小鼠的肌肉力量。与雄性 ICS 暴露的小鼠相比，雌性小鼠表现出更长时间的机械敏感性，同时脊髓和大脑皮层中的 Na、K-ATP 酶活性增强。相反，雄性小鼠大脑皮层中的 Na、K-ATP 酶和谷胱甘肽过氧化物酶活性受到抑制，活性物质水平增加。不同的 5-羟色胺能拮抗剂（pindolol、ketanserin 和 ondansetron）的治疗在 ICS 暴露后，逆转了雌雄小鼠的机械敏感性。MK-801、L-精氨酸和亚甲蓝的给药也阻断了 ICS 暴露的雌性小鼠的机械敏感性。除了 L-精氨酸，MK-801 和亚甲蓝还减轻了 ICS 暴露后雄性小鼠的这种伤害性信号。总之，5-羟色胺能受体、NMDA/NO/cGMP 途径和氧化应激的调节似乎与 ICS 暴露引起的伤害感受行为的性别依赖性有关。
