CD4+ T-cell modulation of visceral nociception in mice.
OBJECTIVE
Although inflammatory and immune cells are present in the gut in the absence of pathology, their presence does not result in sensitization of sensory nerves, implying the existence of a local antinociceptive influence. We hypothesized that a component of the immune system exerts an antinociceptive influence, thus enabling the gut to function in the absence of undue pain or discomfort.


METHODS
Visceromotor responses to colorectal distention were measured in mice with severe combined immune deficiency (SCID) and their wild-type controls.


RESULTS
SCID mice exhibited significantly lower pain thresholds. Transfer of CD4(+) T, but not B lymphocytes, normalized visceral pain in these mice. The restoration of normal visceral nociception following T-cell reconstitution in SCID mice was blocked by naloxone methiodide. Using an enzyme immunoassay and immunohistochemistry for beta-endorphin, we showed that in vitro stimulation of T lymphocytes induced the synthesis and release of beta-endorphin and that transfer of T cells into SCID mice increased the expression of beta-endorphin in the enteric nervous system.


CONCLUSIONS
These findings indicate that the immune system is a critical determinant of visceral nociception and that T lymphocytes provide an important opioid-mediated antinociceptive influence in the gut.
Verma-Gandhu
Monica
M
Intestinal Disease Research Programme, McMaster University Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Bercik
Premysl
P
Motomura
Yasuaki
Y
Verdu
Elena F
EF
Khan
Waliul I
WI
Blennerhassett
Patricia A
PA
Wang
Lu
L
El-Sharkawy
Rami T
RT
Collins
Stephen M
SM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003106:Colon / Q000294:innervation* / Q000473:pathology; D003108:Colonic Diseases / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004576:Electromyography; D004723:Endorphins / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006930:Hyperalgesia / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009619:Nociceptors / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D012680:Sensitivity and Specificity
D004723:Endorphins; D009195:Peroxidase