Background and aims: Fibromyalgia syndrome (FMS) is associated with cognitive dysfunction, involving memory and attention impairments. Memory consolidation requires a correct sleep architecture as well as coordination of oscillatory patterns including cross-frequency coupling between slow waves, spindles and ripples in the hippocampus. The aim of this study is to analyze the oscillatory activity and memory consolidation in a reserpine-induced myalgia model (RIM) in rats. Furthermore, pharmacokinetic/pharmacodynamic (PK/PD) study was carried out to quantify the effect of reserpine on monoamines levels in the progression of disease model.

Methods: Memory impairments were evaluated with Novel Object Recognition Test (NORT). Sleep architecture and oscillatory activity were studied by chronic recording of local field potentials in the hippocampus and somatosensory cortex, and electromyogram in rats subjected to RIM model. For PK/PD study, samples of CSF, plasma and CNS tissue were extracted to determine reserpine and monoamines levels.

Results: Animals showed recognition memory impairments in NORT. Sleep studies showed a distortion of sleep architecture, changes in slow waves and theta activity as well as a diminished phase-amplitude coupling between SW-spindles, SW-ripples and spindle-ripples, several weeks following RIM model. PK/PD study indicated a reduction of the effect of reserpine on monoamines after 48 hours from administration. 

Conclusions: This study reveals memory consolidation impairment in RIM model associated to changes in neural oscillations. This disruption seems independent of the immediate reserpine effect, suggesting plastic changes in neural activity. These findings provide evidence of FMS etiology, and could lead to the establishment of electrophysiological biomarkers for its diagnosis.

DISRUPTED CROSS-FREQUENCY COUPLING RELATED TO COGNITIVE IMPAIRMENTS IN THE RESERPINE-INDUCED MYALGIA MODEL