TY - JOUR T1 - A nonsurgical rat model of an occult chronic neuritis uses tissue repair to create neural pain responses and histology as seen in humans: analgesics and local erythropoietin in the NeuroDigm GEL™ model JF - bioRxiv DO - 10.1101/051979 SP - 051979 AU - Mary R. Hannaman AU - Douglas A. Fitts AU - Rose M. Doss AU - David E. Weinstein AU - Joseph L. Bryant Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/06/051979.abstract N2 - Many humans, suffering from neuropathic pain symptoms, have no clinical evidence of a lesion or disease affecting their somatosensory system. The most common factor, in many of those affected, is that the pain occurred “after” the healing of a soft tissue injury. The reason for the gradual appearance of chronic pain, following soft tissue trauma, could be the universal changes of tissue repair that follow at the injury site. The remodeling of tissue may result in nerve compression, with the delayed onset of pain in some humans. To study this phenomenon, we created a rat model of a mononeuritis with neuropathic pain behavior lasting months using induced tissue remodeling, the prolonged last stage of tissue repair. Thirty-six adult (550g average weight) male rats were randomly assigned to one of three groups: GEL, sham or control. Animals in the control group had a biological gel implanted percutaneously, in the neural tunnel of the distal tibial nerve. Pain behaviors began to appear over 2-3 weeks, with robust persistence of the mechanical hyperalgesia for over 4 months, until the end of the study. Pain behaviors spread contralaterally 2-3 weeks after appearing ipsilaterally. During this time morphine 3 mg/kg, celecoxib 10 mg/kg, gabapentin 25 mg/kg and duloxetine 10 mg/kg were screened 3 times each; all given subcutaneously. Analgesia was similar to the well-characterized responses of humans with post-trauma pain syndromes: morphine had less analgesia over time, celecoxib had no analgesic effects, while gabapentin and duloxetine produced marked analgesia at all times. The anatomic changes seen on histology in the GEL group were consistent with active remodeling of neural tissue. At the conclusion of this study, we tested the analgesic effects of a local injection of the erythropoietin analog, epoetin alfa. The injection of epoetin alfa at the GEL™ procedure site extinguished pain behaviors established for over 4 months. ER -