Nerve growth factor inhibition prevents traumatic neuroma formation in the rat

Nerve growth factor (NGF) is thought to play a role in the pathogenesis of neuroma formation as well as in the development of neuropathic pain. In this study we attempted to antagonize NGF by using trkA-IgG, an inhibitor of NGF, consisting of the NGF receptor linked to an immunoglobulin. It was delivered by an implanted osmotic pump directly to the site of a sciatic nerve transection in 16 rats for 30 days. The animals were monitored daily for the first 2 weeks for evidence of auto-cannibalization (autotomy) of the denervated foot (a sign of neuropathic pain). Four (25%) of the 16 rats receiving trkA-IgG exhibited such cannibalization compared with 9 of 15 control rats (60%) that underwent an identical procedure but were not treated with the trkA-IgG solution. One month after surgery the sciatic nerves and representative dorsal root ganglia (DRG) from these rats were evaluated histologically. Six of the 16 experimental rats (38%) demonstrated histological evidence of neuroma formation compared with 12 of the 15 controls (80%). There were no histological differences between the DRG from the two groups. These results support the notion that inhibiting NGF following peripheral nerve injury in the rat can reduce neuroma formation and neuropathic pain without damaging the cell bodies of the transected neurons.