| Following a nerve injury, there is evidence that there is a large increase in the level of spontaneous firing in the afferent neurons linked to the injury site. The development of this ectopic activity may be particularly important for the development of hyperalgesia, allodynia and ongoing pain associated with nerve injury. In the present study, the relationship between ectopic activity at the very beginning of peripheral nerve injury and neuropathic pain behavior (thermal hyperalgesia and mechanical allodynia) was examined. We used either chronic constriction injury (CCI) or spare nerve injury (SNI) on the sciatic nerve to produce neuropathic pain in rats. In some animals, the injured nerve activity was blocked initially with either bupivacaine or TTX for 5--7 days and 24 hours per day. Animal neuropathic pain behaviors, thermal hyperalgesia and mechanical alodynia, were checked from the first to 2 to 5 months post operation. During this time, there were no significant neuropathic pain behaviors observed on the rats with sciatic nerve injury and initial nerve blockade. We also checked the ectopic activity in rat sciatic nerve with CCI. Initial nerve blockade prevented the subsequent ectopic activity in injured nerve. However, 10 days following CCI or SNI, when rats already presented robust thermal hyperalgesia and mechanical allodynia, this blockade only relieved naturopathic pain temporarily during the blockade. These results suggested that ectopic activity occurring at the early stage of peripheral nerve injury was essential for the development of chronic neuropathic pain. |
