Involvement of TRPV1 and the efficacy of α-spinasterol on experimental fibromyalgia symptoms in mice

• Published in: Neurochemistry international 2020-03, Vol.134, p.104673, Article 104673
• Main Authors: Fischer, Susana Paula Moreira, Brusco, Indiara, Brum, Evelyne Silva, Fialho, Maria Fernanda Pessano, Camponogara, Camila, Scussel, Rahisa, Machado-de-Ávila, Ricardo Andrez, Trevisan, Gabriela, Oliveira, Sara Marchesan
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Chronic Pain - drug therapy; Disease Models, Animal; Fibromyalgia; Fibromyalgia - drug therapy; Hyperalgesia - drug therapy; Male; Mechanical allodynia; Mice; Monoamines; Overt nociception; Pain Measurement - drug effects; Quality of Life; Reserpine; Stigmasterol - analogs & derivatives; Stigmasterol - pharmacology; TRPV Cation Channels - drug effects; TRPV Cation Channels - metabolism
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2020.104673

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. [Display omitted] •Reserpine caused nociceptive/depressive-like behaviours without promoting physical alterations.•TRPV1 is involved in the reserpine-induced nociceptive/depressive-like behaviours.•α-spinasterol, a new TRPV1 antagonist, decreased reserpine-induced nociception-depression.