Central neuronal changes after nerve injury: neuroplastic influences of injury and aging

Peripheral nerve injury produces a hyperexcitability of primary afferents and neurons in the spinal cord that is considered important in the development of nerve injury-induced pain. The authors recently developed a nerve injury model in the trigeminal region of the rat to study the neuronal mechanism of neuropathic pain in the trigeminal system. The escape thresholds to mechanical stimulation applied to the whisker pad area were significantly lower in rats with an inferior alveolar nerve (IAN) transection than those evoked from the contralateral, sham-operated whisker pad. Also, background activity and mechanically evoked responses in infraorbital nerve (ION) afferents and hyperpolarization-activated current (Ih) in trigeminal ganglion ION neurons were increased following IAN transection. Background activity and mechanically evoked responses of wide dynamic range (WDR) neurons in trigeminal subnucleus caudalis on the ipsilateral side relative to the transection were also significantly increased after the operation. A large number of cells expressed c-Fos-like immunoreactivity in the caudal medulla and upper cervical spinal cord following non-noxious mechanical stimulation of the faces of rats with IAN transection. The effect of aging on spinal dorsal horn neurons and the involvement of nerve injury in producing abnormal pain sensation in rats with advancing age were also studied. The incidence of licking behavior in response to noxious radiant heat stimulation of the hind paw was lower in the aged rats than in younger adults, but paw withdrawal latency was shorter and the activities of spinal dorsal horn neurons were higher in the aged rats. Furthermore, the descending inhibitory systems were impaired in the aged rats. These observations suggest that the changes in neuronal activity in the aged rats likely corresponded to the changes observed in the rat model of peripheral nerve injury.