Role of Collagen Conduit With Duloxetine and/or Pregabalin in the Management of Partial Peripheral Nerve Injury.

PURPOSE: The objective of this study was to investigate the analgesic effect of a collagen conduit (Neuragen, Integra LifeSciences Corp, Plainsboro, NJ) using duloxetine (Cymbalta, Lilly, Indianapolis, IN) with or without pregabalin (Lyrica, Pfizer, NY) on pain induced by partial sciatic nerve transection in a rat model. MATERIAL AND METHODS: Adult male Sprague-Dawley rats were divided into 5 groups (n = 10 per group): group 1, nerve damage with no treatment; group 2, nerve damage treated with the application of a collagen conduit and saline; group 3, nerve damage treated with the application of a collagen conduit and duloxetine; group 4, nerve damage treated with the application of a collagen conduit and pregabalin; and group 5, nerve damage treated with the application of a collagen conduit and pregabalin plus duloxetine. Pain levels were evaluated by responses to mechanical and thermal stimuli at baseline before and 3 and 7 days after surgery. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) levels were evaluated in blood, sciatic nerve, and dorsal root ganglion samples collected 7 days after surgery. RESULTS: The group treated with the collagen conduit and pregabalin exhibited markedly less pain 7 days postoperatively in response to mechanical and thermal stimuli compared with the other groups. IL-10 levels were considerably increased in the group treated with pregabalin. The groups treated with a collagen conduit and duloxetine and a combination of pregabalin and duloxetine also exhibited markedly less pain in response to mechanical and thermal stimuli 7 days after surgery compared with the group that had only nerve injury. The decrease in pain using duloxetine was not as robust but was associated with a decrease of TNF-α. The combination of pregabalin and duloxetine resulted in a substantial decrease in IL-6. CONCLUSION: Using a collagen conduit and duloxetine, pregabalin, and their combination helped alleviate neuropathic pain. The mechanism of action might be associated, at least in part, to cytokines.

Interleukin-10 levels in rat models of nerve damage and neuropathic pain.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to play a role in inflammatory and autoimmune disorders as well as in neuropathic pain conditions. The objective of the present study was to assess the levels of IL-10 in rat's dorsal root ganglion (DRG) and the sciatic nerve following four different forms of sciatic nerve injury. The models used to induce the injury included two models of partial nerve injury: partial sciatic ligation (PSL) and chronic constriction injury (CCI), a model of complete sciatic transection (CST) and a model of perineural inflammation with minimal nerve damage (neuritis). Withdrawal responses for mechanical stimulus and withdrawal latency for thermal stimulation were used to measure mechanical and thermal hyperalgesia, respectively, and duration of the nociceptive withdrawal reflex to mechanical stimulus was used to measure mechanical hyperalgesia. The affected and contra-lateral nerves and the affected side DRG IL-10 levels were assessed by the means of enzyme-linked immunosorbent assay (ELISA), 3 and 8 days following the procedure and were compared to naïve rats' IL-10 levels. The rats exposed to CCI and neuritis developed significant mechanical and thermal hyperalgesia as well as mechanical hyperalgesia 3 and 8 days following the surgical procedure. Rats exposed to CST did not respond to mechanical stimulation and developed thermal hypoalgesia 3 and 8 days after the surgery. The DRG IL-10 levels were significantly reduced 3 and 8 days following CCI and PSL, significantly increased 3 and 8 days following CST, and remained unchanged following neuritis. The sciatic nerve IL-10 levels reduced significantly in both injured and contra-lateral nerves 3 and 8 days following CCI and PSL, elevated significantly in the injured but not in the contra-lateral nerve 3 and 8 days following CST and remained unchanged following neuritis. The results of this study suggest that IL-10's role in the neuropathic pain etiology may be specific to nerve injury type. Complete nerve transection increases while partial nerve injury reduces IL-10 levels in the involved nerve, and DRG. Perineural inflammation with minimal nerve damage has no effect on IL-10 levels.