Painful neuromas have been successfully treated by surgical procedures including relocation to muscle, but the underlying molecular mechanism remains unclear. Nerve growth factor (NGF) is secreted by tissues and promotes the expression of ion channels and neuropeptides in sensory neurons involved in pain transmission. We hypothesised that excess of NGF may lead to pain in neuromas and that the efficacy of surgical relocation results from deprivation of NGF, i.e. translocation from NGF-rich regions, particularly sub-cutaneous structures associated with injury or inflammation, to NGF-poor structures such as muscle or bone. Using immunohistological methods with primary antibodies to rhNGF, we report that NGF levels were elevated in 13 painful neuromas in comparison with six control nerves. However, in four painful neuromata re-located into muscle with pain relief, the NGF level was similar to that of controls. NGF levels suggest an explanation for the development of painful neuromas and the efficacy of relocation.

Forty-nine children with distal upper limb nerve injury were studied at a mean follow-up of 2 years 3 months. Patients who were aged 5 years or younger at the time of nerve injury (15/49) had no chronic neuropathic pain symptoms or allodynia. Patients with allodynia on quantitative sensory testing but no spontaneous pain (8/49) were all older than 5 years and those reporting spontaneous chronic neuropathic pain (5/49) were all older than 12 years at the time of injury. Previous studies of adults with similar nerve injuries report chronic hyperaesthesia in up to 40% of cases. Semmes-Weinstein monofilament testing showed a positive correlation between age at injury and abnormal sensory threshold (r = 0.60, P<0.0001). These findings indicate that young children show better sensory recovery and are less likely to develop long-term chronic neuropathic pain syndromes than adults following nerve injury.