Response of GAP-43 and p75 in human neuromas over time after traumatic injury

GAP-43 and p75 are proteins that promote growth cone and neurite formation, elongation, and arborization in regenerating nerve axons. The objectives of this study were to determine whether GAP-43 and the low-affinity nerve growth factor receptor p75 are elevated in traumatic neuromas and whether there is a correlation between the relative amount of GAP-43 or p75 and demographic characteristics such as time elapsed between injury and repair.

Traumatic neuromas from 21 randomly selected patients were studied, and the charts were reviewed. Specimens were collected at the time of nerve resection and grafting. Immunohistochemical analysis was performed on each sample and normal human nerve with antibodies to GAP-43 and p75. Western blot and computerized gel analyses were performed.

All neuroma specimens harvested within 13 months of injury exhibited markedly elevated GAP-43 levels compared with normal nerve. Specimens harvested at 14 months or more after injury showed precipitously lower GAP-43 levels, similar to or less than those of normal nerve. The correlation between the amount of intra-axonal GAP-43 and postinjury time interval was statistically significant, P = 0.0038. High GAP-43 levels were also correlated with transection injury, high postoperative sensory grade, and pain. p75 levels were elevated, without consistent variation in our population.

These preliminary data suggest that the expression of intra-axonal GAP-43 may vary over time after injury, remaining elevated for approximately the first year, then decreasing abruptly to normal or subnormal levels. These results correlate with clinical experience, indicating that peripheral nerves should be repaired relatively early if repair is indicated.