Neuronal Sensitization and Synaptic Facilitation in the Superficial Dorsal Horn of a Rat Reserpine-induced Pain Model

• Published in: Neuroscience Vol. 479; pp. 125 - 139
• Main Authors: Uta, Daisuke, Tsuboshima, Katsuyuki, Nishijo, Hisao, Mizumura, Kazue, Taguchi, Toru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15-12-2021
• Subjects: Animals; Chronic Pain; excitatory and inhibitory postsynaptic transmission; Humans; In vivo patch-clamp recording; monoamine depletion; Neurons; Patch-Clamp Techniques; Posterior Horn Cells; Rats; reserpine; Reserpine - toxicity; Spinal Cord Dorsal Horn; superficial dorsal horn neurons; Synaptic Transmission; RES; chronic pain; SDH; excitatory and inhibitory postsynaptic transmission; FM; vFF; superficial dorsal horn neurons; VEH; EPSC/IPSC; reserpine; In vivo patch-clamp recording; monoamine depletion
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2021.10.010

•Chronic widespread pain like fibromyalgia (FM) is a serious medical problem.•Here we examined the spinal mechanisms using a rat model of FM.•Superficial dorsal horn (SDH) neurons were strongly sensitized in the model.•Increased excitatory postsynaptic input and decreased inhibitory drive to the SDH neurons were also evident.•These spinal mechanisms may be relevant to the nociceptive hypersensitivity in FM.
Chronic widespread pain is one of the important issues to be solved in medical practice. Impaired spinal descending pain inhibitory system due to decreased monoamine neurotransmitters is assumed to cause nociceptive hypersensitivities in chronic painful conditions like that described in patients with fibromyalgia (FM). However, response behaviors and synaptic transmission of the spinal dorsal horn neurons in response to reserpine remain to be clarified. Here we examined the activities of superficial dorsal horn (SDH) neurons, as well as excitatory and inhibitory postsynaptic inputs to SDH neurons, using a putative rat model of FM that was established by injecting reserpine. Extracellular recordings in vivo revealed that SDH neurons were sensitized to mechanical stimulation applied to the neurons’ receptive fields, and the mechanically sensitized neurons were spontaneously more active. The sensitizing effect was evident 1 day and 3 days after the reserpine treatment, but subsided 5 days after the treatment or later. Using patch-clamp recordings in vivo, spontaneous excitatory postsynaptic currents (sEPSCs) to SDH neurons were found to increase in the pain model, while spontaneous inhibitory postsynaptic currents (sIPSCs) to SDH neurons decreased. These results demonstrate that the SDH neurons were strongly sensitized in response to the reserpine treatment, and that increased excitatory and decreased inhibitory postsynaptic inputs could be responsible for the spinal nociceptive hypersensitivity in the putative FM model.