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

Neurochem Int. 2020 Mar;134:104673. doi: 10.1016/j.neuint.2020.104673. Epub 2020 Jan 8.


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.

Keywords: Fibromyalgia; Mechanical allodynia; Monoamines; Overt nociception; Reserpine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Chronic Pain / drug therapy
  • Disease Models, Animal
  • Fibromyalgia / drug therapy*
  • Hyperalgesia / drug therapy*
  • Male
  • Mice
  • Pain Measurement / drug effects
  • Quality of Life
  • Stigmasterol / analogs & derivatives*
  • Stigmasterol / pharmacology
  • TRPV Cation Channels / drug effects*
  • TRPV Cation Channels / metabolism


  • Antidepressive Agents
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • spinasterol
  • Stigmasterol