Antioxidants and Gabapentin Prevent Heat Hypersensitivity in a Neuropathic Pain Model

Background: The involvement of voltage-dependent calcium channels and reactive oxygen species in the pathophysiology of neuropathic pain might justify the preventative administration of antioxidant enzymes, at low doses, in combination with gabapentin (GaP) to maximize its analgesic effect in an experimental model of neuropathic pain in rats. Methods: This work investigated the analgesic effects of these drugs, alone or in combination, by intraperitoneal administration for three consecutive days before (Series I) or after (Series II) a peripheral neuropathy induced by left sciatic nerve ligation. A prospective randomized study was conducted using 96 Wistar rats (50males and 46 females). Mechanical hypersensitivitywas measured with a dynamic plantar anesthesiometer. A hot plate analgesia meter calculated the thermal sensitivity. Side effect profiles for drug combinations were evaluated with a conventional scale to assess levels of sedation interfering with postural control and righting reflexes. Results: Preinjury administration (Series I) of GaP alone prevented the development of mechanical hypersensitivity at the nerve-damage hind paw. When GaP was administered concurrently with superoxide dismutase and catalase, its preventive analgesic effect did not increase. Antioxidants administered alone were completely ineffective at modulating the mechanical or thermal hypersensitivity. When treatments were only delivered following surgery (Series II), only the group receiving combined GaP and antioxidants treatment prior to nerve injury showed higher thermal thresholds from postsurgery days 7-30. Conclusions: These results suggest that preventive antioxidants in combination with GaP provided a synergistic suppression of thermal hypersensitivity that GaP alone cannot produce.