{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T17:28:25Z","timestamp":1791134905486,"version":"4.1.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:p> 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-\u03b1 (TNF-\u03b1) are induced in the spinal cord under various injury conditions and contribute to neuropathic pain. In this study we examined the effect of TNF-\u03b1 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-\u03b1 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-\u03b1 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-\u03b1 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-\u03b1 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. <\/jats:p>","DOI":"10.1152\/jn.01088.2012","type":"journal-article","created":{"date-parts":[[2013,7,18]],"date-time":"2013-07-18T05:37:39Z","timestamp":1374125859000},"page":"1663-1671","source":"Crossref","is-referenced-by-count":39,"title":["Dynamic effects of TNF-\u03b1 on synaptic transmission in mice over time following sciatic nerve chronic constriction injury"],"prefix":"10.1152","volume":"110","author":[{"given":"Hongmei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesia and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of 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