Fibromyalgia is characterised mainly by symptoms of chronic widespread pain and comorbidities like depression. Although these symptoms cause a notable impact on the patient's quality of life, the underlying aetiology and pathophysiology of this disease remain incompletely elucidated. The transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor that is involved in the development of nociceptive and depressive behaviours, while α-spinasterol, a multitarget TRPV1 antagonist and cyclooxygenase inhibitor, presents antinociceptive and antidepressant effects. The present study investigated the involvement of the TRPV1 channel and the possible effects of α-spinasterol on nociceptive and depressive-like behaviours in an experimental fibromyalgia model. The fibromyalgia model was induced with a subcutaneous (s.c.) injection of reserpine (1 mg/kg) once daily for 3 consecutive days in male Swiss mice. Reserpine administration depleted monoamines and caused mechanical allodynia. This dysfunction was inhibited by SB-366791 (1 mg/kg, oral route [p.o.]), a selective TRPV1 antagonist, with a maximum inhibition (Imax) of 73.4 ± 15.5%, or by the single or 3-day-repeated administration of α-spinasterol (0.3 mg/kg, p.o.), with an Imax of 72.8 ± 17.8% and 78.9 ± 32.9%, respectively. SB-366791 also inhibited the increase of the reserpine-induced immobility time, with an Imax of 100%, while α-spinasterol inhibited this parameter with an Imax of 98.2 ± 21.5% and 100%, by single or repeated administration, respectively. The reserpine-induced mechanical allodynia and the thermal hyperalgesia were abolished by TRPV1-positive fibers desensitization induced by previous resiniferatoxin (RTX) administration. In summary, the TRPV1 channel is involved in the development and maintenance of nociception and depressive-like behaviours in a fibromyalgia model, while the α-spinasterol has therapeutic potential to treat the pain and depression symptoms in fibromyalgia patients.

中文翻译：

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TRPV1的参与和α-斯潘甾醇对小鼠实验性纤维肌痛症状的疗效。

纤维肌痛的主要特征是慢性广泛性疼痛和合并症如抑郁症。尽管这些症状会对患者的生活质量产生显着影响，但仍未完全阐明该疾病的潜在病因和病理生理。瞬态受体电位类香草素1型（TRPV1）是一种多态性受体，参与伤害性和抑郁性行为的发展，而α-spinasterol（一种多靶点TRPV1拮抗剂和环加氧酶抑制剂）则具有抗伤害感受和抗抑郁作用。本研究调查了实验性纤维肌痛模型中TRPV1通道的参与以及α-spinasterol对伤害性和抑郁性行为的可能影响。纤维肌痛模型是通过皮下（sc ）在雄性瑞士小鼠中连续3天每天注射一次利血平（1 mg / kg）。利血平给药会耗尽单胺并引起机械性异常性疼痛。该功能障碍被SB-366791（1 mg / kg，口服途径），选择性TRPV1拮抗剂抑制，最大抑制（Imax）为73.4±15.5％，或单次或连续3天给药α-spinasterol（0.3 mg / kg，po），Imax分别为72.8±17.8％和78.9±32.9％。SB-366791还抑制了利血平诱导的不动时间的增加，Imax为100％，而α-spinasterol分别通过单次或重复给药抑制该参数的Imax为98.2±21.5％和100％。利血平诱导的机械性异常性疼痛和热痛觉过敏被先前用树脂毒素（RTX）给药引起的TRPV1阳性纤维脱敏所消除。总而言之，TRPV1通道参与了纤维肌痛模型中伤害感受和抑郁样行为的发生和维持，而α-斯潘甾醇具有治疗纤维肌痛患者的疼痛和抑郁症状的治疗潜力。