A Role for Neuroimmune Signaling in a Rat Model of Gulf War Illness-Related Pain

Details

• Personal Author:
  Grace PM ; Lacagnina MJ ; Li J ; Lorca S ; O'Callaghan JP ; Rice KC ; Sullivan K
• Description:
  More than a quarter of veterans of the 1990-1991 Persian Gulf War suffer from Gulf War Illness (GWI), a chronic, multi-symptom illness that commonly includes musculoskeletal pain. Exposure to a range of toxic chemicals, including sarin nerve agent, are a suspected root cause of GWI. Moreover, such chemical exposures induce a neuroinflammatory response in rodents, which has been linked to several GWI symptoms in rodents and veterans with GWI. To date, a neuroinflammatory basis for pain associated with GWI has not been investigated. Here, we evaluated development of nociceptive hypersensitivity in a model of GWI. Male Sprague Dawley rats were treated with corticosterone in the drinking water for 7 days, to mimic high physiological stress, followed by a single injection of the sarin nerve agent surrogate, diisopropyl fluorophosphate. These exposures alone were insufficient to induce allodynia. However, an additional sub-threshold challenge (a single intramuscular injection of pH 4 saline) induced long-lasting, bilateral allodynia. Such allodynia was associated with elevation of markers for activated microglia/macrophages (CD11b) and astrocytes/satellite glia (GFAP) in the lumbar dorsal spinal cord and dorsal root ganglia (DRG). Additionally, Toll-like receptor 4 (TLR4) mRNA was elevated in the lumbar dorsal spinal cord, while IL-1beta and IL-6 were elevated in the lumbar dorsal spinal cord, DRG, and gastrocnemius muscle. Demonstrating a casual role for such neuroinflammatory signaling, allodynia was reversed by treatment with either minocycline, the TLR4 inhibitor (+)-naltrexone, or IL-10 plasmid DNA. Together, these results point to a role for neuroinflammation in male rats in the model of musculoskeletal pain related to GWI. Therapies that alleviate persistent immune dysregulation may be a strategy to treat pain and other symptoms of GWI. [Description provided by NIOSH]
• Subjects:
  Eye Lighting Mining Occupational Health Safety Sense Organs
• Keywords:
  Author Keywords: Cytokines Cellular Effects Cellular Reactions Central Nervous System Chemical Warfare Agents Chronic Inflammation Cytokines Deoxyribonucleic Acids DNA Gene Expression Glia Gulf War Illness Hypersensitivity Immune Cell Immune Reaction Immune System Laboratory Animals Laboratory Testing Lipids Macrophages Military Personnel MSD Muscle Cells Muscles Musculoskeletal Disorders Nerve Tissue Neuroimmune Neurological Reactions Neuropathy Neurotoxic Agents Pain Pain Tolerance Physiological Stress Ribonucleic Acids RNA Sarin Soldiers Sphingolipids Spinal Cord Toxic Gases

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• ISSN:
  0889-1591
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  418-428
• Volume:
  91
• NIOSHTIC Number:
  nn:20061454
• Citation:
  Brain Behav Immun 2020 Jan; 91:418-428
• Contact Point Address:
  Peter M. Grace, MD Anderson Cancer Center, 6565 MD Anderson Blvd, Houston, TX 77030, USA
• Email:
  pgrace@mdanderson.org
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4) ; Minocycline (CAS RN 10118-90-8) ; Sarin (CAS RN 107-44-8)
• Federal Fiscal Year:
  2021
• Peer Reviewed:
  True
• Source Full Name:
  Brain, Behavior, and Immunity
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:30533d3fa3f9f7c1dc1200ffba913967d4a1a46f48440406a38003e80534481ba286659a63600122897f6fd162076ece298eef359705a7f9282576d1017e7c4d
• Download URL:
  https://stacks.cdc.gov/view/cdc/224984/cdc_224984_DS1.pdf
• File Type:
  [PDF - 1.75 MB ]