Pharmacokinetics of vanillin and its effects on mechanical hypersensitivity in a rat model of neuropathic pain.

The analgesic effects of vanillin on neuropathic pain was evaluated using thermal sensitivity and mechanical allodynia using the sciatic nerve constriction model (n = 30 rats). To determine the pharmacokinetics of vanillin, rats (n = 6/administration route) received either 20 or 100 mg/kg of vanillin i.v. and p.o., respectively. For the pharmacodynamic study, baseline levels for hyperalgesia and allodynia were taken for 5 days prior to surgery. Following surgery each group (n = 6 rats/group) received either vanillin (50 mg/kg or 100 mg/kg), morphine (2 mg/kg or 6 mg/kg) or the vehicle only. Pharmacokinetic results following p.o. administrations are C(max) 290.24 ng/mL, T(max) 4 h, relative clearance 62.17 L/h/kg and T(1/2) 10.3 h. The bioavailability is 7.6%. Mechanical allodynia was decreased on treatment days 1, 2, 3, 5 (p < 0.003) and not on day 4 (p > 0.02) with 50 mg/kg vanillin, whereas at 100 mg/kg p.o. a decrease was noted only on days 7 and 8 (p < 0.003). No effect on hyperalgesia was seen following vanillin administration. In conclusion, vanillin is bioavailable and seems to have an alleviating effect on mechanical allodynia, and not on hyperalgesia, when evaluated with a chronic constriction nerve injury rat model of neuropathic pain.