Antihyperalgesic effects of gabapentin and levetiracetam in a model of post-traumatic epilepsy

Objective: This study aimed to investigate the role of levetiracetam (LEV) and gabapentin (GBP) on mechanical and thermal pain thresholds, as well as n-acetylcysteine (NAC) as an adjuvant, in the pentylenetetrazol (PTZ)-induced post-traumatic epilepsy (PTE) model after mild-traumatic brain injury (TBI) in male Sprague-Dawley rats. Methods: Animals were randomly divided into 7 groups (Control, PTE, PTE+LEV, PTE+GBP, PTE+NAC, PTE+LEV+NAC and PTE+GBP+NAC). Rats received 50 mg kg-1 LEV, 100 mg kg-1 GBP, and combinations of these antiepileptics with 100 mg kg-1 NAC for 14 days after TBI. Results: While the thermal pain threshold decreased significantly in the PTE group (P < 0.05), it increased in the PTE+LEV, PTE+GBP, and PTE+LEV+NAC groups (P < 0.05, P < 0.001 and P < 0.01, respectively). Interestingly, NAC alone did not affect the thermal pain threshold, but the combination of PTE+LEV+NAC increased the thermal pain threshold. Furthermore, PTE+GBP+NAC administration prevented the effect of GBP on the thermal pain threshold. Conclusions: The presented study is the first to examine the effect of LEV and GBP in PTE. It was found that PTE decreased the thermal pain threshold, but LEV and GBP applied for 14 days prevented the decrease in PTE-related pain threshold and increased the thermal pain threshold. NAC, which was used as an adjuvant to support antiepileptic drugs, did not influence the thermal pain threshold alone; however, it increased the pain threshold more by potentiating the effect of LEV. Both LEV and GBP have an antihyperalgesic effect in the PTE model facilitated by PTZ, and NAC further reinforces the antihyperalgesic effect of LEV.