Nöropatik ağrı modelinde levetirasetam'in antihiperaljezik etkilerinin ve bu etkilere katılan mekanizmaların supraspinal düzeyde incelenmesi

Neuropathic pain states disrupt quality of life. There is an evident need for more effective treatments and detailed research for its management. In this study, antihyperalgesic mechanisms of levetiracetam have been investigated at supraspinal level regarding ion channel activities, neurotensinergic and cannabinoidergic systems. Ventral posterolateral nucleus of thalamus was choosen as the site of administration since it functionally participates in pain processing to a great extent. In vivo experiments were performed by e-Von Frey and plantar apparatus for assessing mechanical allodynia and thermal hyperalgesia, respectively. Significant effects of levetiracetam were observed in a dose and time-dependent manner in chronic construction injury model. Neurotensinergic and cannabinoidergic involvement was investigated by pre-treatment of antagonists and significant reversal was demonstrated for both systems. Electrophysiological studies showed that levetiracetam has a tendency to open one or more conductances which are only active at hyperpolarized membrane potentials ranging from -130 to -90 mV, indicating the possible involvement of HCN, Kir or GIRK channels. Utilization of LEV and its derivatives can be assessed as alternative choices in pharmacotherapy of neuropathic pain. Obtained results can guide novel drug development studies towards levetiracetam derivatives for management of neuropathic pain.