B vitamins relieve neuropathic pain behaviors induced by infraorbital nerve constriction in rats

Aims: There is mounting evidence that use of B vitamins can help control neuropathic pain. This study investigated if treatment with B1, B6 and B12 vitamins, alone or in combination with carbamazepine, can ameliorate distinct nociceptive behaviors in a model of trigeminal neuropathic pain. Main methods: Male Wistar rats were submitted to infraorbital nerve constriction or sham surgery and received a 5-day treatment with one of the B vitamins, a single carbamazepine injection or the association of both treatments and were tested for facial thermal and mechanical hyperalgesia at different time intervals. Key findings: Repeated treatment with B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamin) vitamins (at 180, 180 and 18 mg/kg/day, respectively, for 5 days) prevented the development of heat hyperalgesia after infraorbital nerve injury, but only B12 and B6 treatments attenuated cold and mechanical hyperalgesia, respectively. A single injection of carbamazepine (30 mg/kg) significantly reduced thermal, but not mechanical, hyperalgesia after nerve injury. Combinations of lower doses of each B vitamin (B1 and B6 at 18 mg/kg/day and B12 at 1.8 mg/kg/day for 5 days) with carbamazepine (10 mg/kg) markedly reduced heat hyperalgesia after infraorbital nerve injury. Treatment with B12 (1.8 mg/kg/day) combined with carbamazepine (10 mg/kg) also synergized to attenuate cold hyperalgesia at some time points, but combination of B6 (18 mg/kg/day) with carbamazepine (30 mg/kg) failed to modify mechanical hyperalgesia. Significance: We suggest that B vitamins might constitute a relevant adjuvant to control some aspects of the pain afflicting patients suffering from trigeminal neuropathic pain.