Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis

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.

Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium colitis using a new activatable probe

“…Animal studies were approved by the Queen's University Animal Care Committee and carried out in accordance with the guidelines of the Canadian Council on Animal Care. Acute colitis was induced with 3% DSS in their drinking water followed by 2 days of tap water in male C57BL/6 mice (20–25 g; Charles River, Raleigh, NC, USA), as previously described . The severity of colitis was assessed using a disease activity index (DAI) and by measuring colonic length .…”

A role for interleukin 17A in IBD‐related neuroplasticity

“…Additionally, enteric neurons that regulate intestinal motility, blood flow and mucosal secretion are hyperexcitable and exhibit increased excitatory synaptic transmission . Accompanying these electrophysiological changes seen in rodent models of IBD, the structure of nociceptive pathways and enteric nerve circuits also change in response to gut inflammation …”