Changes in c-fos induction in dorsal horn neurons by hindpaw formalin stimulation following tibial neurotomy

Abstract

The hindpaw was partially denervated by the tibial nerve transection in adult rats. At post-transection intervals varying from 2 to 168 days, the hindpaw was stimulated bilaterally by subcutaneous injection of formalin. The excitability of dorsal horn neurons was expressed as the percentage ratio of the number of formalin-induced c-fos protein-like immunoreactive neurons (fos-neurons) on the neurotomized (experimental) side to that on the un-neurotomized (control) side. At 2 days post-injury, a marked reduction in the number of fos-neurons was noted in laminae I–VII of the lumbar spinal cord. Among these, reduction was greatest in the medial 3/8 of laminae I and II (terminal field of the tibial nerve, i.e. tibial territory), and smallest in the lateral 5/8 of the same laminae (the peroneal/hip territory). The low level of c-fos induction remained unchanged for 7 days. At 14 days, the excitability of neurons in all laminae showed a marked increase compared to the post-injury days 2 and 3 combined. Thereafter, the increased level of excitability in the tibial territory was maintained throughout the post-injury period examined in this study. On the other hand, a statistically significant increase in excitability in the peroneal/hip territory was only seen between 14 and 28 days and the excitability almost returned to the baseline (2 days and 3 post-transection combined) level at 42 days. Although deeper laminae (III–VII) contained much less formalin-induced fos-neurons, they also exhibited post-injury excitability changes with a temporal pattern similar to that of the peroneal/hip territory of laminae I and II. Possible mechanisms underlying the post-injury hypersensitivity are discussed in the light of peripheral and central changes following peripheral nerve injuries.