Abstracts

Rationale: Epilepsy and migraine are recognized as comorbid episodic disorders and are believed to share common pathophysiology. Migraine is characterized by a dysfunction of pain processing and migraine sufferers often report the incidence of cutaneous allodynia, defined as hypersensitivity to touch by normally innocuous stimuli. We examined two established models of temporal lobe epilepsy (TLE), Lithium-pilocarpine (LiPC) and intrahippocampal kainic acid (iKA) to develop and validate a model of migraine as a comorbidity of epilepsy. Methods: Lithium-pilocarpine (LiPC) and intrahippocampal kainic acid (iKA) to develop and validate a model of migraine as a comorbidity of epilepsy. Status Epilepticus (SE) was induced using the Lithium-Pilocarpine model or by intrahippocampal injection of Kainate into the hippocampus. Two months after SE, epileptic subjects underwent behavioral tests for (I) cutaneous allodynia using the hot-plate test to measure acute thermal pain evident as latency to paw withdrawl and (II) response to tonic persistent pain, using hindpaw injection of formalin (which elicits a sustained nociceptive stimuli) and measuring total paw-licking time. The analgesic, Sumatriptan, is an agonist of serotonin 5-HT1B/5-HT1D receptors and is used as a treatment for migraine and cluster headaches. We tested the effect of Sumatriptan on epilepsy associated allodynia. Furthermore, we examined the expression of serotonin receptors 5-HT1B/5-HT1D in the periaqueductal gray (PAG), which processes pain and thermal input in the midbrain. Results: Our results show that LiPC and iKA Post-SE animals demonstrated a reduced latency to paw licking compared to vehicle treated animals exposed to temperatures of 47C-50C (i.e. at 48C, Con:50secs vs iKA:25secs; p<0.01, n=10), indicative of thermal allodynia. Intraperitoneal injection of Sumatriptan (300ug/kg) attenuated thermal allodyina in epileptic animals as evident by an increased latency to pawlick in the hot-plate test (p<0.01, n=10). Formalin tests showed a measurable but not statistically significant difference in sensitivity to tonic sustained pain. Immunohistochemistry analyses revealed an increased expression of 5-HT1B and 5-HT1D receptors in the PAG of epileptic animals compared to naïve animals. Conclusions: The data presented provides evidence of the development of nociceptive impairments characteristic of allodynia, in two models of TLE in rats. Additionally, immunohistochemical analysis reveals changes in serotonin receptor expression may contribute to the development of allodynia. Together, our results show the development of allodynia in epileptic animals and suggest that dysfunction of serotonin signaling may contribute to the establishment of epilepsy associated migraine impairments including allodynia.