Terry A. McNearney, M.D., Associate Professor

  • Affiliations: Department of Neuroscience & Cell Biology, Department of Internal Medicine, Department of Microbiology & Immunology, Center for Interdisciplinary Research in Women's Health, Center for Addiction Research & Gulf Coast Pain Consortium
  • Route: 1069, 2.143D Medical Research Building (MRB)
  • Tel: (409) 747-6435
  • Fax: (409) 762-9382
  • tmcnearn@utmb.edu

Terry A. McNearney, M.D.

Education

                                • Undergraduate: Trinity College, Washington, D.C, 1974, B.S. Biology

                                  Medical School: St. Louis Univ Med School, St. Louis, MO, 1981, M.D.

                                  Internship & Residency: Internal Medicine, Baylor College of Medicine, Houston, TX, 1981-1984

                                  Fellowships: (Rheumatology) Washington Univ. School of Medicine, St. Louis, MO    

                                  Clinical: 1984-1985

                                  Research: Dr. John Atkinson’s Laboratory; 1985-1987 

                                  2nd Postdoctoral Fellowship: (Retrovirology), Washington University School of Medicine, St. Louis, MO

                                  (Retrovirology) Dr. Lee Ratner’s Laboratory; 1987-1990

Research Interests

                                • 1. Arthrits Pain and Inflammation

                                  The primary focus of my research since joining NCB has been to study the impact of neurotransmitters on peripheral inflammation, focusing on inflammatory arthritis.  Previous work by the UTMB NCB Pain Group has shown that manipulation of neurotransmitters in the spinal cord can impact pain and inflammation in the periphery. Their groups and others have shown that peripheral inflammation can also impact the impulses of the DRG, spinal cord and higher areas of the brain. An overall theme, detailed below, has been to demonstrate that neurotransmitter receptors that were historically characterized on nervous tissue are also present in peripheral cells, such as cells of joint capsule including synoviocytes, chondrocytes and osteocytes and have physiologic relevance in the periphery. This includes glutamate receptors, TRP receptors and endogenous opioid receptors. These peripheral targets will allow our designing novel safer therapeutic regimens for treating acute and chronic pain and inflammation.

                                  A. The bench research has been an ongoing study of the neuroimmune links in inflammatory arthritis, with focus on the NMDA and TRP receptors and their interactions with proinflammatory cytokines. Our group in collaboration with Dr. Karin N. Westlund, found elevated excitatory amino acids in joint fluids derived from patients with inflammatory arthritis (McNearney et al 2000). We also demonstrated a correlation between elevated levels of synovial fluid excitatory amino acids and proinflammatory cytokines, TNF-a, RANTES and IL-8 (McNearney et al 2004). We have characterized the inotropic and metabotropic glutamate receptors on human synoviocytes (McNearney, submitted).  We determined which TRP receptors and their isoforms were present  and  physiologically significant human synoviocytes (Kochukov et al 2006) and have determined correlations with proinflammatory cytokine, TNF-a  (Kochukov, et al submitted) and the generation of ROS (Kochukov, in preparation).  We also discovered and characterized a novel G-Coupled Protein Receptor in human synoviocytes which may have enhanced physiologic significance in conditions of inflammation and stress (Christensen et al 2005).

                                  B. For the last 4 years, in collaboration with Dr. Karin N. Westlund, our group has investigated the use of gene therapy in inflammatory arthritis, as a peripheral model and pancreatitis, as a visceral model. After targeted injection of an enkephalin-encoding HSV-1 based viral vector, we normalized nociceptive behaviors in animal models. Of great interest, we also significantly blunted the inflammatory response by histologic parameters and downregulated tissue TNF-a, IL-6, COX-2 and RANTES in these models.  This has also led to investigating the neuroimmune link with endogenous enkephalins.

                                  2. Scleroderma

                                   I am a co-I  the NIH fundded  “Sociological, Behavioral and Immunogenetic Determinants of Outcomes in Systemic Sclerosis (Scleroderma,GENISOS”) project for the CORT at UT-Houston Health Sciences Center.  In addition. I have also developed two independent studies utilizing the GENISOS database, which also study the neuroimmune links in Scleroderma.

                                  A. The first study assessed the biological significance of plasma levels of endogenous enkephalins in systemic sclerosis. We found significantly lower levels in patients with Scleroderma, compared to matched normal controls. We also found modest correlations of low met-enkephalin levels with the presence of topoisomerase-I autoantibodies and Raynaud’s phenomenon. Depressed levels of met-enkephalin may be very important in ongoing anoxic, vasogenic injury in Scleroderma, as has been been determined in animal models of anoxic brain injury.

                                  B. The second study is an  ongoing collaboration I have had with Dr Jiande Chen (UTMB Gastroenterology) since 1999, studying Scleroderma GI dysmotility.  Recently we assessed the correlation of gastric peptides and proinflammatory cytokines in Scleroderma GI dysmotility. We found that plasma levels of vasoactive intestinal peptide (VIP) and IL-6 were significantly elevated in Scleroderma patients, compared to normal controls and these levels decreased with TENS application. Plasma IL-6 levels also correlated to gastric myoelectrical activity. One paper showing the normalization of the sympathoparasympathic ratio in Scleroderma patients after TENS treatment and its correlation to perceived functioning has been published. (Sallam, et al 2007).

                                  Publications (selected since 2000, out of 46)

                                                                • McNearney, T.A., Speegle, D., Lawand, N., Lisse, J., and Westlund, K. Excitatory Amino Acid Profiles of Synovial Fluid from Patients with Arthritis. J. Rheumatology. 27(3):739-45, 2000.

                                                                  Lawand, N., McNearney, T.A., and Westlund, K. Amino Acid Release into the Knee Joint: Key Role for Nociception and Inflammation. Pain. 86:69-74, 2000.

                                                                  Reveille, J. Fischbach, M., McNearney, T.A., Friedman, A., Aguila, M., Lisse, J., Fritzler, M., Ahn, C., and Arnett, F. Systemic Sclerosis in Three US Ethnic Groups: A Comparison of Clinical, Sociodemographic, Serologic and Immunogenetic Determinants. Seminars in Arthritis and Rheumatism. 30:332-346, 2001

                                                                  Tew, M., Reveille, J., Arnett, F., Friedman, A., McNearney, T.A., Fischbach, M., Ahn, C., Tan, F. Glutathoine S-transferase Genotypes in Systemic Sclerosis. Genes and Immunity. 2:236-8, 2001.

                                                                  Johnson, R., Tew, M., Reveille, J. Arnett, F., Friedman, A., McNearney, T.A., Fischbach, M., Ahn, C., Tan, F. MMP-14 Levels in Systemic Sclerosis, Genes and Immunity. 2:273-5, 2001.

                                                                  McNearney, T.A., Mei, X., Shrestha, J., Lisse, J., and Chen, J. Characteristics of Surface Electrogastrography in Patients with Systemic Sclerosis, Dig.Dis&Sci, 47:690-698, 2002.

                                                                  Hendiani, J. Goel, N., Lisse, J., Westlund, K., and McNearney, T.A. Mechanical Sensation and Pain Thresholds in Patients with Chronic Arthropathies. J. Pain, 4: 203-11, 2003

                                                                  McNearney, T.A., Baethge, B., Cao, S., Lawand, N., Lisse, J., Alam, R., and K. Westlund. Excitatory Amino Acids, TNF-and Chemokine Levels in Synovial Fluids of Patients with Active Arthropathies, Clin&Exp Immunol 137: 621-627, 2004

                                                                  Wollaston DE, Xiaohong X, Tokumara, O. Chen JDZ, McNearney TA.  Systemic Sclerosis (SSc) patients have unique and persistent alteration in gastric myoelectrical activity (GMA) with acupressure to Neiguan point PC6. J. Rheumatol. 32:494-501, 2005.

                                                                  Christensen, B., Kochukov, M., McNearney, T., Taglialatela, G., and K. Westlund. Proton-sensing G protein-coupled receptor mobilizes calcium in human synoviocytes. Am J Physiol.: Cell Physiol., 289: C601-C608, 2005.

                                                                  Assassi, S., Mayes, M., McNearney, T., Fischbach, M., Reveille, J., Arnett, F., and Tan, F. Polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme show no associations with systemic sclerosis.  The Am J of  Med: 118, p. 907-11, 2005.

                                                                  Sallam, H., McNearney, T., and Chen, J., "Systematic Review: Pathophysiology and Management of Gastrointestinal Dysmotility in Systemic Sclerosis (Scleroderma) Alimentary Pharmacology and Therapeutics, 23:691-712, 2006

                                                                  Kochukov, M, McNearney, TA, Fu, Y, KN Westlund, Thermosensitive TRP ion channels mediate cytosolic calcium response in human synoviocytes (Am J Physiol, Cell Physiol 291: C424-32, 2006.

                                                                  Gourh, Pravitt, Tan, Filemon D., Assassi, Shervin, McNearney, Terry A., Fischbach, Michael, Frank C. Arnett MD a, Maureen D. Mayes Association of the PTPN22  R620W Polymorphism with Topoisomerase-I and Centromere Autoantibody Positive Systemic Sclerosis Arth & Rheum 54:3945-3953, 2006  

                                                                  Terry A. McNearney, John D. Reveille, Michael Fischbach, Alan W. Friedman, Jeffrey R. Lisse, Niti Goel, Filemon K. Tan, Xiaodong Zhou, Chul Ahn, Carol A. Feghali-Bostwick, Marvin Fritzler, Frank C. Arnett and Maureen D. Mayes Pulmonary Involvement in Systemic Sclerosis (SSc) in the GENISOS Cohort:  Associations with Genetic, Serologic, Sociodemographic and Behavioral Factors (Arth Care & Res.57:318-326, 2007

                                                                  Sallam, Hanaa, Terry A. McNearney, Dipti Doshi, Hanaa Sallam  and  JDZ Chen. Electroacupuncture Improves GI Symptoms and Physical Functioning by Balancing the Sympathovagal Activity in Patients with Systemic Sclerosis. Dig Dis & Sci, 52: 1329-37, 2007

                                                                  Junying Xu, Terry A. McNearney, Jiande D Z Chen. Gastrointestinal Electrical Stimulation (GIES) Modulates Gut Appetite Regulatory Hormones to Impact Obesity in Rats.  Obesity Surgery, 17: 406-411, 2007. 

                                                                  Alkassab, Firas, Gourh, Pravitt, Tan, Filemon K., McNearney, Terry, Fischbach, Michael, Chul, Ahn, Arnett, Frank C. and Maureen D. Mayes.  An allograft  inflammatory factor 1 (AIF1) single nucleotide polymorphism (SNP) is associated with anti-centromere antibody positive in systemic sclerosis Rheumatology 46(8): 1248-1251, 2007

                                                                  Khanna, D, Hays, RD, Park, GS, Braun-Moscovici, Y, Mayes, MD, McNearney, TA, Hsu, V., Clements, PJ, and DE Furst. Development of a preliminary scleroderma gastrointestinal tract 1.0) quality of life   instrument, AC&R, 57: 1280-1286, 2007

                                                                  Ying Lu Terry A. McNearney; Weidong Lin; Steven. P. Wilson; David C. Yeomans and Karin N. Westlund, Treatment of inflamed pancreas with enkephalin-encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae. Molecular Therapy 15: 1812-1819, 2007

                                                                  Michelle E. Eisenberg, Prashanth R. Sunkureddi, Bruce A. Baethge, Emilio B. Gonzalez and Terry A. McNearney, Unusual occurrence of renal cell carcinoma (RCC) diagnosed in two Hispanic patients with diffuse systemic sclerosis (dSSc)  J. Clin Rheum, 13: 363-364, 2007

                                                                  Hong Yang, Terry A McNearney, Rong Chu, Ying Lu, Yong Ren, David C Yeomans, Steven P Wilson and Karin N Westlund. Enkephalin-encoding herpes simplex virus-1 decreases   inflammation and hotplate sensitivity in a chronic pancreatitis model. Molecular Pain 2008,  4:8doi:10.1186/1744-8069-4-8

                                                                  Lu, Y, McNearney, TA. Wilson, S, Yeomans, D and KN Westlund. Joint  Capsule Treatment with Enkephalin Encoding HSV-1 Recombinant Vector Reduces Inflammatory Damage and Behavioral Sequelae in Rat Monoarthritis. European Journal of Neuroscience, 27: 1153-1165