Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 24, Issue 7, Pages 1045-1053Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2010.04.001
Keywords
T cells; Opioid peptides; Analgesia; Antinociception; Neuropathic pain; SCID mice
Categories
Funding
- Deutsche Forschungsgemeinschaft, Klinische Forschergruppe [100/2]
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Neuropathic pain is a debilitating consequence of nerve injuries and is frequently resistant to classical therapies. T lymphocytes mediate adaptive immune responses and have been suggested to generate neuropathic pain. In contrast, in this study we investigated T cells as a source of opioidergic analgesic endorphin for the control of augmented tactile sensitivity following neuropathy. We employed in vivo nociceptive (von Frey) testing, flow cytometry and immunofluorescence in wild-type and mice with severe combined immunodeficiency (SCID) subjected to a chronic constriction injury of the sciatic nerve. In wild-type mice, T lymphocytes constituted approximately 11% of all immune cells infiltrating the injury site, and they expressed beta-endorphin and receptors for corticotropin-releasing factor (CRF), an agent releasing opioids from leukocytes. CRF applied at the nerve injury site fully reversed neuropathy-induced mechanical hypersensitivity in wild-type animals. In SCID mice, T cells expressing beta-endorphin and CRF receptors were absent at the damaged nerve. Consequently, these animals had substantially reduced CRF-mediated antinociception. Importantly, the decreased antinociception was fully restored by transfer of wild-type mice-derived T lymphocytes in SCID mice. The re-established CRF antinociception could be reversed by co-injection of an antibody against beta-endorphin or an opioid receptor antagonist with limited access to the central nervous system. We propose that, in response to CRF stimulation, T lymphocytes accumulating at the injured nerves utilize beta-endorphin for activation of local neuronal opioid receptors to reduce neuropathy-induced mechanical hypersensitivity. Our findings reveal beta-endorphin-containing T cells as a crucial component of beneficial adaptive immune responses associated with painful peripheral nerve injuries. (C) 2010 Elsevier Inc. All rights reserved.
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