Injection of activated ERK’s into first order sensory neurons are known to cause long term hyperexcitability that is associated with chronic neuropathic pain. To determine whether there is an activation of ERK’s 1&2, neuromas on branches of either the median, radial, or ulnar nerves were excised from 9 patients ranging in age from 19 to 71 who complained of persistent pain. Control nerves were segments of grafts from 5 patients. Antibody staining of Western blots showed that the neuromas varied in the total amount of the 2 kinases, but that each neuroma had similar amounts of each kinase. The ERKs are activated by a double phosphorylation that is recognized by antibody Ab-PP. Western blots that were duplicates of the ones above were exposed to Ab-99 to detect only the activated kinase. Interestingly, both kinases were rarely active in the same tissue and the kinases tended to be more active in the neuromas. We measured the density of each stained band and calculated the ratio of active to inactive kinase for each neuroma. The ratios were normalized and a calculation of the mean relative value for ERK1 yielded 48.0 in the neuromas versus 20.0 for the control. The comparable mean for ERK2 was 53.0 in the neuromas and 44.0 in the control. These results indicate that the ERK’s are persistently active in painful neuromas and suggest that they participate in regulating the genes that lead to chronic pain. The stress activated kinase JNK-46 has been implicated in a variety of events after a nerve injury, yet it’s association with neuroma pain has not been determined. To correlate JNK-46 activity with neuroma formation we used an antibody that recognizes only the phosphorylated (activated) form of the kinase. When Western blots from each neuroma were probed with the antibody, the highest level of JNK-46 activity per microgram of protein was found in 2 of the neuromas. Active JNK-46 was barely detectable in the other neuromas, however, whereas one of the controls also had a high level of the active kinase. We conclude from this analysis that the activity of JNK-46 does not correlate directly with the formation of painful neuromas.