title: Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats.
abstract: After experimental nerve injuries that extensively disrupt axons, such as chronic constriction injury, immune cells invade the nerve, related dorsal root ganglia (DRGs), and spinal cord, leading to hyperexcitability, raised sensitivity, and pain. Entrapment neuropathies, such as carpal tunnel syndrome, involve minimal axon damage, but patients often report widespread symptoms. To understand the underlying pathology, a tube was placed around the sciatic nerve in 8-week-old rats, leading to progressive mild compression as the animals grew. Immunofluorescence was used to examine myelin and axonal integrity, glia, macrophages, and T lymphocytes in the nerve, L5 DRGs, and spinal cord after 12 weeks. Tubes that did not constrict the nerve when applied caused extensive and ongoing loss of myelin, together with compromise of small-, but not large-, diameter axons. Macrophages and T lymphocytes infiltrated the nerve and DRGs. Activated glia proliferated in DRGs but not in spinal cord. Histologic findings were supported by clinical hyperalgesia to blunt pressure and cold allodynia. Tubes that did not compress the nerve induced only minor local inflammation. Thus, progressive mild nerve compression resulted in chronic local and remote immune-mediated inflammation depending on the degree of compression. Such neuroinflammation may explain the widespread symptoms in patients with entrapment neuropathies.
authors.affiliation: School of Health and Rehabilitation Sciences, The University of Queensland, Queensland, Australia. annina.schmid@neuro-research.ch
authors.forename: Annina B
authors.initials: AB
authors.lastname: Schmid
authors.forename: Michel W
authors.initials: MW
authors.lastname: Coppieters
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Ruitenberg
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: McLachlan
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology; D008297:Male; D020078:Neurogenic Inflammation / Q000150:complications / Q000209:etiology* / Q000276:immunology*; D059408:Pain Management; D017288:Pain Threshold; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011948:Receptors, Antigen, T-Cell; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015740:Calcitonin Gene-Related Peptide; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D014446:Tyrosine 3-Monooxygenase; C067980:CD68 antigen, human; D000097382:CD68 Molecule