Abstract:Objective: To explore the change and its significance of the numbers of neurons and synapses in the rat spinal dorsal horn at 7 and 28 days after L5 spinal nerve ligation (SNL). Methods: 29 male SD rats aged 3 months were randomly divided into two groups: L5 unilateral SNL group (10 animals) and sham-operated group (13 animals). The mechanical withdrawal thresholds (PWT) of bilateral hind paws were measured every 4 days, starting from 1 day before the operation until 28 days post-operation. At 7 and 28 days post-operation, the L5 segment of the spinal cord was removed. Paraffin-embedded sections were prepared and stained with Nissl’s method and synaptophysin immunohistochemistry to mark neurons and synapses (presynaptic axon terminals). The numbers of neurons and synapses (per unit length of the spinal cord) in the L5 spinal cord dorsal horn were estimated with the stereological optical disector. Results: The percentage reductions of PWT on the operation side were significantly lower in the SNL group than in the sham-operated group. Compared with the contralateral non-operated side, the number of synapses and the numerical ratio of synapses to neurons were unchanged on the operation side in the SNL group at 7 days, and significantly increased by 23.5% and 17.4%, respectively, at 28 days. Conclusion: SNL-induced changes in synaptic plasticity associated with neuropathic pain (NP) require prolonged development. This delayed neural remodeling may constitute the structural underpinnings of chronic pain maintenance.