title: Dynamic effects of TNF-α on synaptic transmission in mice over time following sciatic nerve chronic constriction injury.
abstract: Nerve injury-induced central sensitization can manifest as an increase in excitatory synaptic transmission and/or as a decrease in inhibitory synaptic transmission in spinal dorsal horn neurons. Cytokines such as tumor necrosis factor-α (TNF-α) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-α in modulating excitatory and inhibitory synaptic input to spinal substantia gelatinosa (SG) neurons over time in mice following chronic constriction injury (CCI) of the sciatic nerve. Whole cell patch-clamp studies from SG neurons showed that TNF-α enhanced overall excitability of the spinal cord early in time following nerve injury 3 days after CCI compared with that in sham control mice. In contrast, the effects of TNF were blunted 14 days after CCI in nerve-injured mice compared with sham surgery mice. Immunohistochemical staining showed that the expression of TNF-α receptor 1 (TNFR1) was increased at 3 days but decreased at 14 days following CCI in the ipsilateral vs. the contralateral spinal cord dorsal horn. These results suggest that TNF-α acting at TNFR1 is important in the development of neuropathic pain by facilitating excitatory synaptic signaling in the acute phases after nerve injury but has a reduced effect on spinal neuron signaling in the later phases of nerve injury-induced pain. Failure of the facilatory effects of TNF-α on excitatory synaptic signaling in the dorsal horn to resolve following nerve injury may be an important component in the transition between acute and chronic pain conditions.
authors.affiliation: Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhang
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dougherty
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000503:physiopathology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism / Q000503:physiopathology; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
keywords: CCI; hyperalgesia; spinal synaptic transmission; substantia gelatinosa