Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect.

Neuroscience letters 2010 Jun 18; In press

Orhan C CE, Onal A, Ulker S

Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.

Recent studies have revealed that T lymphocytes play a role in neuropathic pain following nerve injury in rats through releasing several cytokines. Sirolimus is an immunosupressive antibiotic inhibiting T cell activation. This study aimed to determine the effect of sirolimus on hyperalgesia and allodynia and on serum and spinal cord TNF-alpha, IL-1beta and IL-6 levels in rat neuropathic pain. Neuropathic pain was induced by loose ligation of the sciatic nerve and evaluated by tests measuring the mechanical hyperalgesia and allodynia. Sirolimus (0.75 and 1.5mg/kg) was administered intraperitoneally once every 3 days for 2 weeks (7 doses totally). This dosing regimen revealed acceptable blood concentrations in neuropathic rats. Chronic constriction injury of the sciatic nerve resulted in hyperalgesia and allodynia. Serum levels of cytokines remained unchanged in neuropathic rats. However, TNF-alpha, but not IL-1beta or IL-6, protein level was increased in the spinal cord tissue as evaluated by Western blotting analysis. Treatment with sirolimus resulted in antihyperalgesic and antiallodynic effects and prevented the increased spinal cord TNF-alpha level. It seems that sirolimus could be a promising immunosupressive agent in the treatment of neuropathic pain.

Keywords: neuropathic pain sirolimus