Novel Use of Perineural Pregabalin Infusion for Analgesia in a Rat Neuropathic Pain Model

BACKGROUND: The anticonvulsant drugs pregabalin and gabapentin are often used systemically to treat some forms of chronic neuropathic pain. However, many patients report side effects serious enough to cause discontinuation of the drug. Here we present evidence that pregabalin may block neuropathic pain when applied to the site of nerve injury in a rat neuropathic pain model. METHODS: Forty male Sprague Dawley rats were randomized into 4 groups: sciatic nerve crush injury with perineural pregabalin treatment (treatment), crush injury with perineural saline treatment (saline control), crush injury with subcutaneous pregabalin treatment (systemic drug control), and sham surgery (sham surgery control). Animals received either continuous infusions of 1% pregabalin for 7 days (treatment and systemic control) or saline (saline control) and were tested for pain behaviors using incapacitance meter, guarding scores, and radiant heat withdrawal latency (Hargreaves method). Nerves were studied using histology and immunohistochemistry for α(2)δ-1 receptors thought to mediate the central analgesic action of pregabalin. RESULTS: Treatment rats had significantly better guarding scores than systemic drug controls or saline controls (P < 0.0001) and had significantly better incapacitance scores than systemic drug controls and saline controls (P ≤ 0.001). Hargreaves method data showed hypoalgesia in all injured animals with no difference among injured groups (P = 0.80). Qualitatively, immunohistochemistry likely showed equivalent expression of the α(2)δ-1 calcium channel at the injured nerve site in all nerve-injured animals. CONCLUSIONS: Perineural pregabalin administration produced superior analgesia compared with that of systemic pregabalin in this neuropathic pain model. Perineural pregabalin treatment may provide a useful alternative to systemic pregabalin treatment for neuropathic pain.