Investigation of the effects of mianserin on diabetic neuropathic pain in rats with streptozotocin-induced diabetes

In this thesis study, therapeutic effect of agomelatine administration on hyperalgesia and allodynia, which developed in streptozotocin (STZ)-diabetic rats were investigated using several experimental pain-induction methods. Acute and subacute antinociceptive effects of agomelatine were evaluated by tail clip and hot-plate tests. Further, the effect of this drug on neuropathic pain was examined by various experimental models in which mechanical or thermal stimuli were applied. Dynamic plantar aesthesiometer test was performed for mechanical allodinia; Randal-Sellito test was performed for mechanical hyperalgesia; warm plate (38oC) test was performed for thermal allodinia; Hargreave's and cold plate (4oC) tests were performed for thermal hyperalgesia. Obtained data showed that, acute agomelatine administration, at 40 and 80 mg.kg-1 doses causes opioid mediated strong antinociceptive effect in normoglycemic rats. Besides, findings obtained from diabetic rats indicated that subacute administration (7 and 14 days) of agomelatine at 40 and 80 mg.kg-1 doses significantly improves neuropathy induced hyperalgesia and allodinia. Agomelatine treatment restored hyperalgesia and allodinia responses of the diabetic rats to the levels of normoglycemic control animals. Agomelatine was found to be effective as reference drug pregabalin (10 mg.kg-1).Similar to acute antinociceptive effect of agomelatine, antihyperalgesic and antiallodinic effects of this drug abolished by the naloxone administration. This finding pointed out that opiod mechanisms also involved in the therapeutic activity of repeated agomelatine administrations. Considering that agomelatine has antidepressant, anxiolytic and antinociceptive effects at the same time, this drug seem to has an advantage for treating painful diabetic neuropathy as well as diabetes induced affective disorders such as depression and anxiety, which have high incidence in the diabetic population. This advantage is important for clinicians to provide the ability to avoid polypharmacy.