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NEUROREGULATION AND MOTILITY

Lymphocyte-mediated regulation of -endorphin in the myenteric plexus

¹Intestinal Disease Research Programme and ²Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Submitted 18 July 2006 ; accepted in final form 1 September 2006

Lymphocytes are antinociceptive and can modulate visceral pain perception in mice. Previously, we have shown that adoptive transfer of CD4⁺ T cells to severe combined immune-deficient (SCID) mice normalized immunodeficiency-related visceral hyperalgesia. Pain attenuation was associated with an increase in -endorphin release by T cells and an upregulation of -endorphin in the enteric nervous system. In this study, we investigated the relationship between T cells and opioid expression in the myenteric plexus. We examined opioid peptide and receptor expression in the myenteric plexus in the presence and absence of mucosal T cells. We found a positive association between T cells and -endorphin expression; this was accompanied by a downregulation of the µ-opioid receptor (MOR). In vitro, T helper (Th) type 1 and type 2 cytokine stimulation of CD4⁺ T cells or isolation of T cells from in vivo Th-polarized mice did not increase T cell release of -endorphin or the induction of -endorphin expression in the myenteric plexus. However, exogenous -endorphin did upregulate -endorphin expression, and both cycloheximide and naloxone methiodide inhibited peptide upregulation. Therefore, our results suggest that nonpolarized CD4⁺ T cells release -endorphin, which, through an interaction with MOR, stimulates an upregulation of -endorphin expression in the myenteric plexus. Thus, we propose that the mechanism underlying lymphocyte modulation of visceral pain involves T cell modulation of opioid expression in the enteric nervous system.

enteric nervous system; opioid; CD4⁺ T cells