Nerve decompression surgery suppresses TNF‐ɑ expression and T cell infiltration in a rat sciatic nerve chronic constriction injury model

Decompression surgery (DS) is a standard treatment for chronic nerve compression injuries; however, the mechanisms underlying its effects remain unclear. Here, we investigated the effects of DS on messenger RNA (mRNA) expression of tumor necrosis factor‐α (TNF‐α) and T cell recruitment in a rat sciatic nerve (SN) chronic constriction injury (CCI) model. Male Wistar rats were subjected to CCI to establish a model of SN injury (CCI group). DS, in which all ligatures were removed, was performed 3 days after CCI surgery (CCI + dec group). Mechanical sensitivity was assessed using the von Frey test 3, 7, and 14 days after the CCI surgery. Gene expression of Tnfa, Cd3, Cxcl10, and immunolocalization of TNF‐α and the pan T cell marker, CD3, was evaluated using quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. In addition, the effects of TNF‐α on Cxcl10 expression and CXCL10 protein production were evaluated using qPCR and enzyme‐linked immunosorbent assay in SN cell culture. Rats that received DS had significantly higher withdrawal threshold levels than those in the CCI group. In addition, Tnfa, Cd3, and Cxcl10 mRNA expression increased following CCI. DS suppressed this elevated expression, with the CCI + dec group showing significantly reduced expression levels compared to the CCI group. Furthermore, TNF‐α induced Cxcl10 expression and CXCL10 protein production in SN cell culture. Therefore, DS reduced TNF‐α expression and T cell recruitment in the rat SN CCI model. These observations may partly explain the mechanism underlying the therapeutic effects of DS.

[1]  Xiang Xu,et al.  TNF-α augments CXCL10/CXCR3 axis activity to induce Epithelial-Mesenchymal Transition in colon cancer cell , 2021, International journal of biological sciences.

[2]  Sheng Yi,et al.  Characteristics of cytokines in the sciatic nerve stumps and DRGs after rat sciatic nerve crush injury , 2020, Military Medical Research.

[3]  J. Zimmermann,et al.  Reduced inflammatory response and accelerated functional recovery following sciatic nerve crush lesion in CXCR3-deficient mice , 2020, Neuroreport.

[4]  R. Medcalf,et al.  Activated CD8+ T Cells Cause Long-Term Neurological Impairment after Traumatic Brain Injury in Mice. , 2019, Cell reports.

[5]  J. Pollock,et al.  Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages , 2019, International journal of molecular sciences.

[6]  S. Ohtori,et al.  Wrapping With Basic Fibroblast Growth Factor‐Impregnated Collagen Sheet Reduces Rat Sciatic Nerve Allodynia , 2019, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[7]  A. Kavelaars,et al.  T Cells as an Emerging Target for Chronic Pain Therapy , 2019, Front. Mol. Neurosci..

[8]  S. Ohtori,et al.  Vein wrapping promotes M2 macrophage polarization in a rat chronic constriction injury model , 2018, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[9]  S. Ohtori,et al.  Vein wrapping facilitates basic fibroblast growth factor‐induced heme oxygenase‐1 expression following chronic nerve constriction injury , 2017, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[10]  S. Hsieh,et al.  Nerve Decompression Improves Spinal Synaptic Plasticity of Opioid Receptors for Pain Relief , 2018, Neurotoxicity Research.

[11]  I. Jou,et al.  Effects of decompression on behavioral, electrophysiologic, and histomorphologic recovery in a chronic sciatic nerve compression model of streptozotocin-induced diabetic rats , 2017, Journal of pain research.

[12]  S. Matsuzaki,et al.  Peripheral administration of interleukin-13 reverses inflammatory macrophage and tactile allodynia in mice with partial sciatic nerve ligation. , 2017, Journal of pharmacological sciences.

[13]  N. Kiguchi,et al.  Macrophage-T Cell Interactions Mediate Neuropathic Pain through the Glucocorticoid-induced Tumor Necrosis Factor Ligand System* , 2015, The Journal of Biological Chemistry.

[14]  M. Takechi,et al.  Itraconazole inhibits TNF-α-induced CXCL10 expression in oral fibroblasts. , 2015, Oral diseases.

[15]  Bernard Choi,et al.  Early Surgical Decompression Restores Neurovascular Blood Flow and Ischemic Parameters in an in Vivo Animal Model of Nerve Compression Injury. , 2014, The Journal of bone and joint surgery. American volume.

[16]  S. Ohtori,et al.  Vein wrapping for chronic nerve constriction injury in a rat model: study showing increases in VEGF and HGF production and prevention of pain-associated behaviors and nerve damage. , 2014, The Journal of bone and joint surgery. American volume.

[17]  J. Zou,et al.  CD8+ T Cell-Mediated Cytotoxicity toward Schwann Cells Promotes Diabetic Peripheral Neuropathy , 2013, Cellular Physiology and Biochemistry.

[18]  S. Raimondo,et al.  Role of inflammatory cytokines in peripheral nerve injury☆ , 2012, Neural regeneration research.

[19]  Gila Moalem-Taylor,et al.  Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis , 2012, PAIN®.

[20]  E. Senba,et al.  Site-specific subtypes of macrophages recruited after peripheral nerve injury , 2011, Neuroreport.

[21]  B. Digiovanni,et al.  Peripheral nerve entrapments of the lower leg, ankle, and foot. , 2011, Foot and ankle clinics.

[22]  Chun Cheng,et al.  Tumor necrosis factor‐alpha inhibits Schwann cell proliferation by up‐regulating Src‐suppressed protein kinase C substrate expression , 2009, Journal of neurochemistry.

[23]  Z. Lee,et al.  CXCL10 and autoimmune diseases. , 2009, Autoimmunity reviews.

[24]  H. Rittner,et al.  Immune cell-derived opioids protect against neuropathic pain in mice. , 2009, The Journal of clinical investigation.

[25]  P. Sacerdote,et al.  Transient early expression of TNF-α in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy , 2008, Neuroscience Letters.

[26]  Seungbok Lee,et al.  Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis. , 2008, Arthritis and rheumatism.

[27]  S. Hsieh,et al.  Effects of decompression on neuropathic pain behaviors and skin reinnervation in chronic constriction injury , 2007, Experimental Neurology.

[28]  S. Meuth,et al.  T cell infiltration after chronic constriction injury of mouse sciatic nerve is associated with interleukin-17 expression , 2006, Experimental Neurology.

[29]  S. McMahon,et al.  Role of the Immune system in chronic pain , 2005, Nature Reviews Neuroscience.

[30]  J. H. Robinson A systematic review of reviews comparing the effectiveness of endoscopic and open carpal tunnel decompression. , 2005, Plastic and reconstructive surgery.

[31]  G. Moalem,et al.  T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats , 2004, Neuroscience.

[32]  T. Pritsch,et al.  [Carpal tunnel syndrome]. , 2004, Harefuah.

[33]  D. Steinberg Surgical release of the carpal tunnel. , 2002, Hand clinics.

[34]  C. Sommer,et al.  Tumor necrosis factor-α (TNF) regulates the expression of ICAM-1 predominantly through TNF receptor 1 after chronic constriction injury of mouse sciatic nerve , 2002, Acta Neuropathologica.

[35]  J. Firrell,et al.  The prevalence and characteristics of nerve compression symptoms in the general population. , 2001, The Journal of hand surgery.

[36]  J. Cui,et al.  Possible role of inflammatory mediators in tactile hypersensitivity in rat models of mononeuropathy , 2000, PAIN.

[37]  T. Hartung,et al.  Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury , 2000, Brain Research.

[38]  D. Tracey,et al.  Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury , 2000, Pain.

[39]  A. Zlotnik,et al.  Chemokines: a new classification system and their role in immunity. , 2000, Immunity.

[40]  Simon A. Jones,et al.  Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes , 1996, The Journal of experimental medicine.

[41]  T. Yaksh,et al.  Quantitative assessment of tactile allodynia in the rat paw , 1994, Journal of Neuroscience Methods.

[42]  J. Katz,et al.  A self-administered questionnaire for the assessment of severity of symptoms and functional status in carpal tunnel syndrome. , 1993, The Journal of bone and joint surgery. American volume.

[43]  Gary J. Bennett,et al.  A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man , 1988, Pain.

[44]  M. Zimmermann,et al.  Ethical guidelines for investigations of experimental pain in conscious animals , 1983, Pain.

[45]  W. Dixon,et al.  Efficient analysis of experimental observations. , 1980, Annual review of pharmacology and toxicology.