Abstract
Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.
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We gratefully acknowledge the technical support of Iva Kosatka and Margaret O’Reilly.
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This work was supported by funding from the Canadian Institutes of Health Research (C.A., A.L., S.V.), the Crohn’s and Colitis Foundation of Canada (S.V., A.L.) and the Ontario Ministry of Research and Innovation (A.L.). T.L. holds a fellowship from Alberta Innovates Health Solutions and CIHR/CAG.
Contributions to this work were as follows: J.B., C.A., D.M., T.L., S.V. and A.L. designed the research study; J.B., J.X., D.M. and T.L. performed the experiments; J.B., C.A., D.M., T.L., S.V. and A.L. analysed the data; J.B., C.A., D.M., T.L., S.V. and A.L. wrote the manuscript.
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Benson, J.R., Xu, J., Moynes, D.M. et al. Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis. Cell Tissue Res 356, 309–317 (2014). https://doi.org/10.1007/s00441-014-1832-x
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DOI: https://doi.org/10.1007/s00441-014-1832-x