CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain.
We previously reported leukocytic infiltration into the lumbar spinal cord in a rodent spinal nerve L5 transection (L5Tx) neuropathic pain model. Here, we further investigated the role of infiltrating T lymphocytes in the etiology of persistent pain following L5Tx. T lymphocyte-deficient nude mice showed no evident mechanical hypersensitivity after day 3 of L5Tx compared to wild-type BALB/c mice. Through FACS analysis, we determined that significant leukocytic infiltration (CD45(hi)) into the lumbar spinal cord peaked at day 7 post L5Tx. These infiltrating leukocytes contained predominantly CD4(+) but not CD8(+) T lymphocytes. B lymphocytes, natural killer cells and macrophages were not detected at day 7 post L5Tx. No differences in the activation of peripheral CD4(+) T lymphocytes were detected in either the spleen or lumbar lymph nodes between L5Tx and sham surgery groups. Further, CD4 KO mice displayed significantly decreased mechanical hypersensitivity after day 7 of L5Tx, and adoptive transfer of CD4(+) leukocytes reversed this effect. Decreased immunoreactivity of glial fibrillary acidic protein observed in CD4 KO mice post L5Tx indicated possible T lymphocyte-glial interactions. These results strongly support a contributing role of spinal cord-infiltrating CD4(+) T lymphocytes versus peripheral CD4(+) T lymphocytes in the maintenance of nerve injury-induced neuropathic pain.
Cao
Ling
L
Department of Anesthesiology, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.
DeLeo
Joyce A
JA
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D005260:Female; D008161:Lumbosacral Region; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013116:Spinal Cord / Q000276:immunology*; D013127:Spinal Nerves / Q000276:immunology* / Q000473:pathology / Q000601:surgery
D015704:CD4 Antigens