Evaluation of reserpine-induced fibromyalgia in mice: A comparative behavioral, neurochemical, and histological assessment of two doses

Abstract

Fibromyalgia (FM) is a chronic pain disorder characterised by widespread musculoskeletal pain, fatigue, and cognitive disturbances. Due to its complex and poorly understood pathophysiology, reliable animal models are essential for research. Reserpine is commonly used to induce FM in animals, effectively replicating key symptoms such as widespread pain, hypersensitivity, and mood disturbances. However, the varying doses used in studies and the often unclear rationale for dose selection have led to a lack of standardisation for this model. In this study, we investigated the effects of commonly used reserpine doses (0.25 and 0.5mg/kg) to induce FM in mice. Following three consecutive days of subcutaneous reserpine injections, we conducted detailed behavioural assessments and microscopic examinations of tissue changes. We also compared the effects of the two reserpine doses on serotonin, norepinephrine, glutamate, interleukin (IL)-1β, and tumour necrosis factor (TNF)-α levels in the brain and spinal cord. The behavioural assessment demonstrated that both doses of reserpine had nearly the same effect relatively early after administration. Histological examination revealed neurotoxic effects of reserpine, particularly in the hippocampus and thalamus, which was more obvious at day 11 with the 0.5mg/kg dose. Furthermore, this dose significantly altered all neurotransmitter levels compared with the control group. While the effect of the 0.25mg/kg dose on neurotransmitter levels was limited, it altered the IL-1β and TNF-α levels in the brain and spinal cord. Our findings indicate that injecting reserpine at 0.25 or 0.5mg/kg for three consecutive days is effective in inducing FM-like pain in mice, characterised by mechanical and thermal hypersensitivity, along with associated depression and motor deficits. However, the 0.5mg/kg dose is optimal for inducing persistent neurochemical alterations and histopathological changes, lasting up to 10 days following the initial injection.