Epilepsy may cause increased pain sensitivity: Evidence from absence epileptic WAG/Rij rats

Abstract

Objective: The comorbidity of epilepsy and pain disorders as well as effectiveness of certain therapeutic approaches in both conditions attracted attention to epilepsy-pain interactions. This lead to the discovery of significantly shared pathophysiological mechanisms although many aspects remain largely unknown. To test the hypothesis that epilepsy may be associated with altered pain sensitivity, we analyzed interictal pain sensitivity using epilepsy prone WAG/Rij rats, a genetic model exhibiting age-related-onset absence epilepsy.

Methods: Two series of experiments were conducted. In experiment I, pain sensitivity of symptomatic WAG/Rij rats were compared with age-matched control Wistar rats. In experiment II, pain sensitivity of WAG/Rij rats were monitored longitudinally when they were presymptomatic (at 2months) and symptomatic (after maturation, at 8months), and compared with age-matched control Wistar rats. Pain sensitivity was assessed by applying heat stimuli to hind paws and measuring the paw-withdrawal latency using thermal plantar analgesia meter in awake and freely moving animals. All pain measurements were made during the interictal period, confirmed by simultaneous electroencephalography through intracranially implanted electrodes.

Results: In experiment I, the interictal pain withdrawal latency of symptomatic WAG/Rij rats was significantly shorter than control Wistar rats (P<0.01). In experiment II, WAG/Rij rats had significantly shorter latency of withdrawal response than control Wistar rats, both at presymptomatic (P<0.05) and symptomatic stage (P<0.0001). Matured (8months old) control Wistar rats demonstrated significantly increased withdrawal latency compared to the 2months animals (P<0.01), but the WAG/Rij rats did not (P>0.5).

Conclusion: Epileptic WAG/Rij rats present significantly increased pain sensitivity when compared to control Wistar rats, suggesting comorbidity of epilepsy and pain.

Keywords: Epilepsy; Genetic absence epilepsy; Pain; Pain threshold; WAG/Rij rats.