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Open Access Highly Accessed Review

TNF-α and neuropathic pain - a review

Lawrence Leung123* and Catherine M Cahill145

Author Affiliations

1 Centre for Neurosciences Studies, 18, Stuart Street, Queen's University, Kingston, Ontario K7L 3N6, Canada

2 Centre of Studies in Primary Care, Queen's University, Kingston, Ontario K7L 5E9, Canada

3 Department of Family Medicine, 220 Bagot Street, Queen's University, Kingston, Ontario K7L 5E9, Canada

4 Department of Pharmacology & Toxicology, 18, Stuart Street, Queen's University, Kingston, Ontario K7L 3N6, Canada

5 Department of Anesthesiology, 76 Stuart Street, Queen's University, Kingston, Ontario K7L 2V7, Canada

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Journal of Neuroinflammation 2010, 7:27  doi:10.1186/1742-2094-7-27

Published: 16 April 2010

Abstract

Tumor necrosis factor alpha (TNF-α) was discovered more than a century ago, and its known roles have extended from within the immune system to include a neuro-inflammatory domain in the nervous system. Neuropathic pain is a recognized type of pathological pain where nociceptive responses persist beyond the resolution of damage to the nerve or its surrounding tissue. Very often, neuropathic pain is disproportionately enhanced in intensity (hyperalgesia) or altered in modality (hyperpathia or allodynia) in relation to the stimuli. At time of this writing, there is as yet no common consensus about the etiology of neuropathic pain - possible mechanisms can be categorized into peripheral sensitization and central sensitization of the nervous system in response to the nociceptive stimuli. Animal models of neuropathic pain based on various types of nerve injuries (peripheral versus spinal nerve, ligation versus chronic constrictive injury) have persistently implicated a pivotal role for TNF-α at both peripheral and central levels of sensitization. Despite a lack of success in clinical trials of anti-TNF-α therapy in alleviating the sciatic type of neuropathic pain, the intricate link of TNF-α with other neuro-inflammatory signaling systems (e.g., chemokines and p38 MAPK) has indeed inspired a systems approach perspective for future drug development in treating neuropathic pain.