神経因性疼痛モデルにおける疼痛関連行動と神経損傷の相関に関する検討

抄録

Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw skin on day 32. The present results suggested that the severity of neuropathic pain was related with the degrees of both degeneration and/or regeneration of myelinated fibers and of functional damage of unmyelinated fibers.