Infralimbic cortex neurostimulation attenuates nociceptive and affective manifestations in a reserpine-induced fibromyalgia model.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain, frequently accompanied by cognitive deficits and psychiatric symptoms. FM has been associated with large-scale functional alterations of brain networks involved in pain processing, particularly the default mode network (DMN) and the pain salience network. The infralimbic cortex (IL), a region of the medial prefrontal cortex (mPFC) considered part of the DMN, is functionally connected to regions involved in salience processing. However, the role of the IL in modulating FM-related manifestations remains poorly understood. Therefore, the objective of this study was to investigate the effect of IL neurostimulation on pain modulation and anxiety- and depression-like behaviors in an experimental rat model of FM. IL neurostimulation was performed using a deep-brain stimulation (DBS) device (20 μA/100 Hz/15 s) 14 days after the experimental induction of FM using the reserpine pharmacological model (1 mg/kg, s.c., once daily for three consecutive days). IL neurostimulation reduced mechanical allodynia in the von Frey test and decreased both anxiety- and depression-like behaviors assessed using the open field, splash, and forced swim (FST) tests. These findings suggest that the IL exerts an inhibitory role in the modulation of pain and psychiatric comorbidities in FM, suggesting potential circuits between the IL and the salience network in modulating the manifestations of FM.