Alkaloid fraction of Psychotria nemorosa reduces fibromyalgia-like symptoms in mice

Abstract Fibromyalgia is a syndrome characterised by widespread chronic pain, often accompanied by comorbidities such as fatigue, anxiety, and depression. Pharmacological treatments offer only partial relief of symptoms and can cause significant adverse effects. Therefore, finding new treatments is crucial. Psychotria nemorosa , a species rich in indole alkaloids, has garnered interest due to its acute antinociceptive properties observed in vivo and its effects on monoamine oxidase A and B in in vitro assays. Additionally, alkaloids are recognised for their antinociceptive effects, as well as their anxiolytic and antidepressant properties. Therefore, we examined the effects of the alkaloid fraction of P. nemorosa in a model that simulates fibromyalgia symptoms in male Swiss. Initially, the antinociceptive effects of the fraction (3, 10, and 30 mg/kg, administered orally) were tested in capsaicin- and formalin-induced nociception, and potential adverse effects on locomotion and body temperature were evaluated. Next, the 30 mg/kg dose was tested in the reserpine-induced fibromyalgia model for mechanical, cold, and heat sensitivity, muscle strength, and behaviours resembling depression and anxiety. The P. nemorosa alkaloid fraction (30 mg/kg) decreased capsaicin- and formalin-induced nociception without affecting locomotion or body temperature. It also alleviated mechanical and cold allodynia, thermal hyperalgesia, muscle fatigue, and anxiety-like behaviour caused by reserpine, although it did not show an antidepressant-like effect. These results suggest that the P. nemorosa alkaloid fraction has therapeutic potential for treating fibromyalgia pain and related conditions such as fatigue and anxiety. They also emphasise the need for further research into its mechanisms and its long-term safety.