T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats.
A catastrophic consequence of peripheral nerve injury is the development of abnormal, chronic neuropathic pain. The inflammatory response at the injury site is believed to contribute to the generation and maintenance of such persistent pain. However, the physiological significance and potential contribution of T cells to neuropathic pain remains unclear. Here we show that T cells infiltrate injured sciatic nerves following chronic constriction injury (CCI), but not uninjured nerves. Congenitally athymic nude rats, which lack mature T cells, developed a significantly reduced mechanical allodynia and thermal hyperalgesia following CCI, compared with their heterozygous littermates. To understand further the role played by different T-cell subsets, we generated polarized populations of type 1 and type 2 T cells, with different cytokine secretion profiles, from spleens of sciatic nerve-injured heterozygous rats. Passive transfer of type 1 T cells, which produce proinflammatory cytokines, into nude rats enhanced the recipients' pain hypersensitivity to a level similar to that of heterozygous donor rats. In contrast, passive transfer of polarized type 2 T cells, which produce anti-inflammatory cytokines, into heterozygous rats modestly though significantly attenuated their pain hypersensitivity. Thus, injection of type 1 and type 2 T-cell subsets produces opposing effects on neuropathic pain. These findings suggest the modulation of the T-cell immune response as a potential target for the treatment of neuropathic pain.
Moalem
G
G
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267-0521, USA.
Xu
K
K
Yu
L
L
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D003251:Constriction, Pathologic / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007839:Functional Laterality; D006930:Hyperalgesia / Q000503:physiopathology; D007116:Immunization, Passive / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009437:Neuralgia / Q000276:immunology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000503:physiopathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D011923:Rats, Nude; D009418:S100 Proteins / Q000378:metabolism; D012584:Sciatic Nerve / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000276:immunology / Q000503:physiopathology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification / Q000502:physiology*; D013997:Time Factors
D016207:Cytokines; D008565:Membrane Proteins; D009418:S100 Proteins