Investigation of neuropathic pain sensitivity and development mechanism in peripheral nerve damage-induced model in absence epileptic WAG/RIJ rats

The comorbidity of pain syndromes with epilepsy is very common. Neuropathic pain, caused by the disease or a lesion in the peripheral or central nervous system, is among these syndromes. Furthermore, the balance between inhibition and excitation in the nervous system is impaired in both, individuals with epilepsy and neuropathic pain. These raises the question that there may be some common mechanisms underlying these two conditions. In this thesis, how epilepsy changes the pain sensitivity in a model of neuropathic pain, a chronic pain condition, and some possible developmental mechanisms are examined. This study consists of two parts. Firstly, neuropathic pain was triggered in WAG/Rij, an age-dependent onset absence epilepsy model, and Wistar rats, their healthy ancestors. Chronic constriction injury of the sciatic nerve for triggering model was used. Afterwards, hyperalgesia and allodynia were evaluated using thermal plantar test and electronic von Frey which are behavioral pain tests. Secondly, the expression levels of transient receptor potential vanilloid receptor 1, N-methyl D-aspartate, interleukin-1 beta and neurokinin 1 receptors were investigated by real-time polymerase chain reaction in dorsal root ganglion, trigeminal ganglion, rostral ventromedullar medulla, reticular thalamic nucleus, periaquaductal gray matter and anterior cingulate cortex where points are pain is produced, transported and modulated. In behavioral pain protocol it was determined that, both in heat and mechanical stimulation, following sciatic nerve ligation the pain threshold was decreased. This increased pain sensitivity was evident in both healthy Wistar and epileptic WAG/Rij rats. The findings of molecular analysis was not ideally correlated with the behavioral increased pain sensitivity findings. Results from this thesis study indicated that neuropathic pain develops in epilepsy. But, these findings fail to clarify whether central or peripheral mechanism contribute to this and it was concluded that both mechanisms could be contributing to this phenomenon in this model. Key words: Epilepsy, neuropathic pain, sciatic nerve injury, TRPV1