Investigation of antihyperalgesic and antiallodinic effects of linalool in rats with diabetic neuropathy

In this thesis, it was aimed to investigate the effects of linalool on diabetes-induced neuropathic pain. Hyperalgesia and allodynia induced by diabetes in rats were evaluated by Randall-Selitto and Dynamic plantar tests, respectively. Administration of linalool at doses of 75 and 150 mg.kg -1 for 7 and 14 days significantly prolonged the shortened paw withdrawal thresholds of diabetic rats in both tests. Obtained data demonstrated that linallol ameliorated mechanical stimulus-induced hyperalgesia and allodynia at doses administered, comparable to gabapentin. On the other hand, linalool administrtions did not cause any change in blood glucose levels and motor activity values of diabetic rats. These findings indicate that the pharmacological effects observed in this study were not due to an antidiabetic activity or any impairment in motor performance. Within the scope of the study, mechanistic studies were carried out with agents named α-methyl-para-tyrosine (catecholamine synthesis inhibitor), yohimbine (α 2 - adrenergic receptor blocker), ICI 118.551 (β 2 -adrenergic receptor blocker) and sulpiride (D 2 /D 3 blocker) to investigate the mechanisms underlying the antihyperalgesic and antiallodynic effects of linalool. Pre-administrations of these agents abolished the antihyperalgesic and antiallodynic effects of linalool. These findings indicated that an intact catecholaminergic system should be present for linalool to have antihyperalgesic and antiallodynic activity, and revealed that α 2 -adrenergic, β 2 -adrenergic and D 2 /D 3 - dopaminergic receptors contributed to these effects.