Stigmasterol attenuates nociplastic pain and fatigue-like symptoms in a reserpine-induced fibromyalgia model in mice.

Fibromyalgia is a widespread painful condition prevalent in women. The main manifestations include spontaneous pain, mechanical and thermal allodynia, and comorbid symptoms such as fatigue and migraine, impacting the patients’ quality of life. Treatments for this disease have limited effectiveness and cause adverse effects, making it necessary to search for alternative therapies. Stigmasterol is a phytosterol with antinociceptive effects in clinically relevant experimental pain models. Therefore, we investigated stigmasterol’s effect on painful and fatigue-like symptoms in a reserpine-induced experimental fibromyalgia model in mice. Adult female C57BL/6 mice received reserpine subcutaneously (1 mg/kg) once a day for three consecutive days. Mice submitted to the fibromyalgia model developed plantar mechanical and cold allodynia, mechanical-induced affective-motivational behaviour, heat thermal hyperalgesia, loss of muscle strength, and periorbital mechanical allodynia. Stigmasterol (0.3, 1, and 3 mg/kg, single dose, orally) reduced plantar mechanical allodynia and mechanical-induced affective-motivational behaviour in a time- and dose-dependent manner. Stigmasterol (3 mg/kg, orally) also reduced cold allodynia, heat thermal hyperalgesia, periorbital mechanical allodynia, and loss of muscle strength caused by reserpine, without causing motor impairment. Pregabalin (30 mg/kg, orally), Food and Drug Administration-approved for fibromyalgia treatment, and sumatriptan (0.6 mg/kg, orally), an anti-migraine drug, were used as reference drugs and reduced the nociceptive behaviours caused by reserpine. Our findings demonstrate that stigmasterol attenuated nociplastic pain and fatigue-like symptoms in the reserpine-induced fibromyalgia model in mice, highlighting its potential as a promising therapeutic candidate for alleviating pain-related symptoms in fibromyalgia.