The Effects of a Proximal Crush on Pain in a Rat Neuroma Model

Abstract

Grant support received from: 2016 AFSH Basic Science Grant Other: Washington University, Checkpoint Surgical (M. Wood) A nerve crush induces an alternative growth program at the neuron level compared with the transection injury, which may modulate the development of pain. Our study evaluated the effect of performing a proximal nerve crush in a rat sciatic neuroma model to evaluate its efficacy as an adjunctive intervention for prevention and/or treatment of painful neuromas. The study consisted of 2 arms: (1) neuropathic pain prevention with a 2-week secondary intervention, and (2) neuropathic pain treatment with a 6-week secondary intervention. Male Lewis rats (n = 9) had an initial sciatic transection proximal to the trifurcation, followed by an intervention consisting of a sham surgery, proximal crush, or neuroma resection. The animals were tested weekly for pain-related behavior utilizing cold allodynia testing. Dorsal root ganglions were harvested at 5 months for both arms to assess pain-related gene expression profiles. Neuropathic pain prevention: Cold allodynia response slowly increased in all groups after the initial injury. Following the intervention to mitigate the development of cold allodynia responses, by day 56, the proximal crush group had a cold allodynia time of 3.6 ± 3.5 (mean ± standard deviation, seconds), which was significantly lower than the neuroma resection group, 17.6 ± 13.1 P < .01. Neuropathic pain treatment: Cold allodynia response was allowed to plateau following the initial sciatic transection, to a maximum of 22.6 ± 6.8. Following crush intervention, cold allodynia was only 9.5 ± 7.8 by week 8, 17.7 ± 7.6 in the resection group, and 17.1 ± 8.3 in the sham surgery group. These differences were not significant. Pain-related gene expression analysis is ongoing. •A proximal crush intervention modulates pain-related behavior in this rodent sciatic neuroma model when performed early.•Intervention after the development of peak pain (late intervention) was not effective in modulating pain behavior.•This study suggests a potential benefit of a proximal nerve crush as an adjunctive procedure when performed early, at the time of nerve transection or amputation. This research was supported by a Basic Science Grant from the American Foundation for Surgery of the Hand.