title: The dissipation of neuropathic pain paradoxically involves the presence of tumor necrosis factor-alpha (TNF).
abstract: Neuropathic pain, a chronic disabling pain arising from nerve injury, develops a central component. In brain neurons, tumor necrosis factor-alpha (TNF) levels intensify and TNF-inhibition of norepinephrine (NE) release, dependent upon alpha(2)-adrenergic activation, amplifies during neuropathic pain onset. TNF-inhibition of NE release transforms to facilitation in the hippocampus of rats administered antidepressants (treat neuropathic pain), contemporaneous with decreased neuron TNF. Therefore, adrenergic drugs inhibit increased pain sensitivity (hyperalgesia) by decreasing TNF production, thereby inducing increased NE release. This study examined TNF- and alpha(2)-adrenergic-regulated NE release from hippocampal slices during both the onset and dissipation of hyperalgesia during sciatic nerve chronic constriction injury (CCI). The enhanced inhibition of NE release by TNF at peak hyperalgesia (day-8) transformed to facilitation of NE release at days 12, 14, 16, and 21 post-CCI, corresponding to dissipation of hyperalgesia. Chronic antidepressant drug administration alone to rats results in similar findings. Rats administered the antidepressant amitriptyline (10 mg/kg, i.p., 60 min) at day-8 post-CCI, no longer exhibited hyperalgesia. Interestingly, the presynaptic response to TNF transformed to facilitation of NE release. While TNF directs the development of hyperalgesia, it is also involved in the resolution of pain, a possible mechanism for management of chronic pain.
authors.affiliation: Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Ignatowski
authors.forename: Reeteka
authors.initials: R
authors.lastname: Sud
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Reynolds
authors.forename: Paul R
authors.initials: PR
authors.lastname: Knight
authors.forename: Robert N
authors.initials: RN
authors.lastname: Spengler
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology* / Q000627:therapeutic use
chemical_list: D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine