Intrathecal administration of antioxidants attenuates mechanical pain hypersensitivity induced by REM sleep deprivation in the rat

Background: Sleep deprivation as well as peripheral neuropathy and cutaneous neurogenic inflammation has a facilitatory effect on pain perception. Herewestudied whether oxidative stress-related mechanisms in the spinal cord that have been shown to contribute to pain facilitation in peripheral neuropathy and cutaneous neurogenic inflammation play a role in sleep deprivation-induced pain hypersensitivity. Methods: Flower pot method was used to induce rapid eye movement sleep deprivation (REMSD) of 48 h duration in the rat that had a chronic intrathecal (i.t.) catheter for spinal administration of drugs. Pain behavior was assessed by determining the monofilament-induced limb withdrawal response. Results: REMSD of 48 h produced mechanical hypersensitivity that was attenuated in a dose-related fashion by i.t. administration of two different antioxidants, phenyl-N-tert-butylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1 oxyl (TEMPOL). While both antioxidants attenuated mechanical pain behavior also in control animals, their effects were significantly stronger after REMSD than in control conditions. Conversely, i.t. administration of a reactive oxygen species (ROS) donor, tert-butylhydroperoxide (t-BOOH), in control animals produced pain hypersensitivity that was prevented by i.t. pretreatment with an antioxidant, TEMPOL. I.t. treatment with PBN or TEMPOL at the currently used doses failed to influence motor behavior in the Rotarod test. Conclusions: The results indicate that among common mechanisms contributing to mechanical pain hypersensitivity following sleep deprivation as well as nerve injury or neurogenic inflammation is oxidative stress in the spinal cord. Implications: Compounds with antioxidant properties might prove useful in suppressing the vicious pronociceptive interaction between chronic pain and sleep-deprivation. (C) 2011 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.