ACTIVITY OF THIOCTIC ACID ENANTIOMERS ON SPINAL CORD CHANGES CONSEQUENT TO PERIPHERAL NERVE INJURY

Peripheral neuropathies are disorders characterized by hyperalgesia and allodynia with impaired muscular sensitivity and functions. Oxidative stress, which is an imbalance between the production of free radicals and the antioxidant defence mechanisms is increased in peripheral neuropathies. Antioxidants and in particular thioctic acid, have been proposed as potential therapeutic agents for treating and/or preventing several pathologies related to increased oxidative stress. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (-)-thioctic acid and in the racemic form (+/-)-thioctic acid. The present study has assessed if chronic constriction injury (CCI) induced by loose ligation of the sciatic nerve, is accompanied by spinal cord changes and if thioctic acid enantiomers treatment has any therapeutic activity. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), used as a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY) taken as a control group. Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 14 days with (+/-)-(250 mmol/kg/day and 125 mmol/kg/day), (+)-(125 mmol/kg/day) or (-)-(125 mmol/kg/day) thioctic acid. Effects elicited by thioctic acid were compared with those of pregabalin (300 mmol/kg/day), an anticonvulsant used for treating neuropathic pain. Analysis was focused on injury phenomena at level of dorsal root ganglia and spinal cord and was made using immunochemical and immunohistochemical techniques. An increase of oxidative stress markers was observed after CCI of the sciatic nerve. An obvious astrogliosis and neuronal damage independent by activation of apoptotic processes occurred primarily in the spinal cord posterior horn. Treatment with thioctic acid reduced oxidative stress and astrogliosis in spinal cord. (+)-Thioctic acid and the higher dose of (+/-)-thioctic acid were the most active. (-)-Thioctic acid and pregabalin were without effect. The above results demonstrated a spinal cord damage after peripheral nerve injury and a neuroprotective effect induced by thioctic acid. These findings suggest a neuroprotective activity of thioctic acid on central nervous system lesions consequent to CCI and that the compound may represent an option for entrapment neuropathies treatment.