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Keywords:

  • colitis;
  • dorsal root ganglia;
  • rat;
  • sympathetic sprouting;
  • tyrosine hydroxylase

Abstract

Background  Peripheral irritation-induced sensory plasticity may involve catecholaminergic innervation of sensory neurons in the dorsal root ganglia (DRG).

Methods  Catecholaminergic fiber outgrowth in the thoracolumbar DRG (T13-L2) was examined by tyrosine hydroxylase (TH) immunostaining, or by sucrose-potassium phosphate-glyoxylic acid histofluorescence method. TH level was examined by Western blot. Colonic afferent neurons were labeled by retrograde neuronal tracing. Colitis was induced by intracolonic instillation of tri-nitrobenzene sulfonic acid (TNBS).

Key Results  The catecholaminergic fibers formed ‘basket-like’ structures around the DRG cells. At 7 days following TNBS treatment, the number of DRG neurons surrounded by TH-immunoreactive fibers and the protein levels of TH were significantly increased in T13, L1, and L2 DRGs (two- to threefold, P < 0.05). The DRG neurons that were surrounded by TH immunoreactivity were 200 kDa neurofilament-positive, but not isolectin IB4-positve or calcitonin gene-related peptide-positive. The TH-immunoreactive fibers did not surround but adjoin the specifically labeled colonic afferent neurons, and was co-localized with glial marker S-100. Comparison of the level of TH and the severity of colonic inflammation showed that following TNBS treatment, the degree of colonic inflammation was most severe at day 3, subsided at day 7, and significantly recovered by day 21. However, the levels of TH in T13-L2 DRGs were increased at both 3 days and 7 days post TNBS treatment and persisted up to 21 days (two- to fivefold increase, P < 0.05) as examined.

Conclusions & Inferences  Colonic inflammation induced prolonged catecholaminergic innervation of sensory neurons, which may have relevance to colitis-induced chronic visceral hypersensitivity and/or referred pain.