CD4+ T-cell modulation of visceral nociception in mice

Gastroenterology. 2006 May;130(6):1721-8. doi: 10.1053/j.gastro.2006.01.045.


Background & aims: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Colon / innervation*
  • Colon / pathology
  • Colonic Diseases / immunology
  • Colonic Diseases / pathology
  • Disease Models, Animal
  • Electromyography
  • Endorphins / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Hyperalgesia / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Nociceptors / immunology*
  • Peroxidase / metabolism
  • Sensitivity and Specificity


  • Endorphins
  • Peroxidase