Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain

• Published in: Neuroscience 2001-01, Vol.103 (2), p.529-539
• Main Authors: Sweitzer, S, Martin, D, DeLeo, J.A
• Format: Article
• Language: English
• Subjects: Animals; astrocytes; Biological and medical sciences; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; cytokines; Disease Models, Animal; Drug Therapy, Combination; Etanercept; Female; Immunoglobulin G - pharmacology; Injections, Spinal; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - metabolism; interleukin-6; Interleukin-6 - metabolism; Male; Medical sciences; microglia; Nervous system (semeiology, syndromes); Neuralgia - drug therapy; Neuralgia - immunology; Neuralgia - metabolism; Neuroglia - immunology; Neuroglia - metabolism; Neurology; Neurons - immunology; Neurons - metabolism; nociception; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; Sex Factors; Sialoglycoproteins - pharmacology; Spinal Cord - cytology; Spinal Cord - metabolism; Spinal Cord - physiology; Spinal Nerves - physiopathology; Spinal Nerves - surgery; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00574-1

The expression of interleukin-1β and tumor necrosis factor has previously been shown to be up-regulated in the spinal cord of several rat mononeuropathy models. This present study was undertaken to determine whether blocking the action of central interleukin-1β and tumor necrosis factor attenuates mechanical allodynia in a gender-specific manner in a rodent L5 spinal nerve transection model of neuropathic pain, and whether this inhibition occurs via down-regulation of the central cytokine cascade or blockade of glial activation. Interleukin-1 receptor antagonist or soluble tumor necrosis factor receptor was administered intrathecally via lumbar puncture to male Holtzman rats in a preventative pain strategy, in which therapy was initiated 1 h prior to surgery. Administration of soluble tumor necrosis factor receptor attenuated mechanical allodynia, while interleukin-1 receptor antagonist alone was unable to decrease allodynia. Interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor, administered to both male and female rats in a preventative pain strategy, significantly reduced mechanical allodynia in a dose-dependent manner ( P