Focal peripheral nerve injury induces leukocyte trafficking into the central nervous system: potential relationship to neuropathic pain.
The present study was undertaken to determine whether leukocytes are recruited into the spinal cord following a peripheral L5 spinal nerve transection that results in mechanical allodynia (increased tactile sensitivity behavior correlates with neuropathic pain). In rats subjected to bone marrow irradiation, donor-specific major histocompatibility complex (MHC) class I (I1-69) positive peripheral immune cells trafficked to the L5 spinal cord in response to an L5 spinal nerve injury. The number of I1-69 positive cell profiles increased over time and correlated with increased mechanical allodynia. At early time points following injury, I1-69 positive immune cells co-regionalized with the expression of the macrophage marker ED2. At later time points following injury, some of the infiltrating immune cells did not co-regionalize with the macrophage marker ED2. At no time did the infiltrating cells co-regionalize with the neuronal marker (NeuN). Both macrophage-like morphology and T cell-like morphology were observed in the I1-69 positive cellular infiltrate. Conversely, animals that underwent sham surgery demonstrated little mechanical allodynia and a minimal number of infiltrating peripheral immune cells. In a separate group of rats, infiltration of CD3+ T-lymphocytes was confirmed at 14 days post-nerve transection. This study demonstrates trafficking of leukocytes into the lumbar spinal cord at time points that correlate with mechanical allodynia suggesting a role of central neuroinflammation in persistent neuropathic pain.
Sweitzer
Sarah M
SM
Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03756, USA.
Hickey
William F
WF
Rutkowski
Maria D
MD
Pahl
Janice L
JL
DeLeo
Joyce A
JA
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003714:Denervation; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D009437:Neuralgia / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology; D011828:Radiation Chimera; D011843:Radiculopathy / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology*; D013127:Spinal Nerves / Q000276:immunology / Q000293:injuries*; D013601:T-Lymphocytes / Q000276:immunology*
D015395:Histocompatibility Antigens Class I