Treatment of Neuropathic Pain Using 1-O-Hexyl-2,3,5- Trimethylhydroquinone (HTHQ)

Abstract

Neuropathic pain is caused by a primary lesion or injury to the nervous system and can be spontaneous, with no obvious peripheral stimulus. Pain results from the complex interplay between signaling systems and individual perception. Neuropathic and chronic pain effect more than 100 million Americans while costing the country billions of dollars annually to treat and manage. The purpose of this research study was to discover if preemptive or post-injury treatment with 1-O-Hexyl-2,3,5- trimethylhydroquinone (HTHQ), a hydroquinone monoalkyl ether known for its antioxidative abilities, effectively alleviates neuropathic pain induced by partial sciatic nerve ligation in rats. In order to test the effectiveness of HTHQ in reducing neuropathic pain, we began by taking preliminary baseline behavior assessments to test animal pain response prior to injury. Some animals were treated with HTHQ for three consecutive days prior to the performance of partial sciatic nerve ligation (pSNL) surgery, while some were treated each day beginning four days after the induction of injury. Animal behavior was observed again for 10 days after nerve injury and drug treatment. The levels of antioxidant and pro-inflammatory proteins were analyzed using the western blot technique in order to determine the effectiveness of HTHQ at treating neuropathic pain. Preliminary findings suggests that treatment with HTHQ three days prior to nerve ligation surgery showed an increase in antioxidant catalase, an enzyme responsible for converting hydrogen peroxide to water and oxygen, in the spinal cords of injured rats compared to those that were not treated 10-days after nerve injury. Our findings also demonstrate that rats treated with HTHQ three days prior to nerve injury showed an increase in antioxidative protein SOD2 but also decreases the expression of pro-inflammatory protein IL-1ß compared to vehicle treated neuropathic rats. There were no therapeutic changes seen in rats treated with HTHQ four days after pSNL surgery.