[Analysis of Plastic Changes in Spinal Neurons in Fibromyalgia and the Exploration of Therapeutic Agents]

Fibromyalgia (FM) is a chronic disorder characterized by widespread pain and various accompanying symptoms, with complex mechanisms involving both peripheral and central nervous systems that remain unclear. Herein, we introduce a study employing a reserpine-induced rat model of FM, investigating the spinal dorsal horn in particular. In reserpine-induced FM model rats, we observed pronounced mechanical hypersensitivity of cutaneous and muscular C-fiber nociceptors. Moreover, increased expression of the ASIC3 (one of acid-sensing ion channel) in dorsal root ganglia implicated its role in peripheral sensitization. Within the spinal dorsal horn, enhanced microglial activation was evident; pharmacological inhibition with minocycline significantly attenuated mechanical hyperalgesia, indicating the critical involvement of microglial activity in central pain processing. Furthermore, patch-clamp recordings revealed altered synaptic transmission characterized by enhanced spontaneous excitatory postsynaptic currents (EPSCs) and reduced inhibitory postsynaptic currents (IPSCs), contributing to heightened pain signaling in the FM model. These findings suggest that an imbalance of intensified excitatory and diminished inhibitory neurotransmission in the spinal dorsal horn leads to impaired sensory gating and augmented nociceptive transmission to higher centers, a pivotal mechanism in the pathophysiology of FM.