Peripheral nerve injury-induced rearrangement of neural circuit in the spinal dorsal horn revealed by cross-correlation analysis

Peripheral nerve injury often induces abnormal pain states, such as hyperalgesia and allodynia. In this study, we attempted to elucidate how neurons are synaptically integrated into the neuronal circuitry in the spinal dorsal horn and how synaptic connectivity patterns among dorsal horn neurons are altered by peripheral nerve injury. Experiments were performed on 6-8-week-old ICR mice. Partial sciatic nerve ligation was performed. Transverse slices of the lumbar spinal cord were prepared. Spike activities were simultaneously recorded from multiple neurons in the superficial dorsal horn (SDH) using a multi-electrode array system, and cross-correlograms between spike trains of neuron pairs were constructed. In sham-operated control mice, except for the flat cross-correlogram, the most common pattern was a cross-correlogram suggestive of common excitatory synaptic inputs to neuronal pairs. Peripheral nerve ligation increased the incidences of cross-correlograms suggestive of common excitatory synaptic inputs and excitatory synaptic connections, and decreased that of inhibitory synaptic connections. Additionally, bath-applied capsaicin, an agonist for transient receptor potential vanilloid 1 receptor, increased the frequency of action potentials. The effects of capsaicin stimulation on the incidence of cross-correlograms with various patterns were significantly different between sham-operated control and sciatic nerve-ligated mice. The present observations seem to indicate that neurons in the SDH form excitatory and/or inhibitory synapses with nearby neurons, and that synaptic connections among neurons in the SDH may remarkably change after the development of neuropathic pain.