The refined biomimetic NeuroDigm GEL™ Model of neuropathic pain in the mature rat.

Abstract

Background: Many humans suffering with chronic pain have no clinical evidence of a lesion or disease. They are managed with a morass of drugs and invasive procedures. Opiates usually become less effective over time. In many, their persistent pain occurs after the healing of a soft tissue injury. Current animal models of neuropathic pain typically create direct neural damage with open surgeries using ligatures, neurectomies, chemicals or other forms of deliberate trauma. However, we have observed clinically that after an injury in humans, the naturally occurring process of tissue repair can cause chronic neural pain. Methods: We demonstrate how the refined biomimetic NeuroDigm GEL™ Model, in the mature male rat, gradually induces neuropathic pain behavior with a nonsurgical percutaneous implant of tissue-derived hydrogel in the musculo-fascial tunnel of the distal tibial nerve. Morphine, Celecoxib, Gabapentin and Duloxetine were each screened in the model three times each over 5 months after pain behaviors developed. A pilot study followed in which recombinant human erythropoietin was applied to the GEL neural procedure site. Results: The GEL Model gradually developed neuropathic pain behavior lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses had profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months. Histology revealed a site of focal neural remodeling, with neural regeneration, as in human biopsies. Conclusion: The refined NeuroDigm GEL™ Model induces localized neural remodeling resulting in robust neuropathic pain behavior. The analgesics responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin appears to heal the ectopic focal neural site, as demonstrated by the extinguishing of neuropathic pain behavior present for over 4 months.