Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a rat model of colitis

Tsuyoshi Majima, Yasuhito Funahashi, Naoki Kawamorita, Shun Takai, Yoshihisa Matsukawa, Tokunori Yamamoto, Naoki Yoshimura, Momokazu Gotoh

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Aims: We investigated whether spinal cord microglia are involved in colon-to-bladder neural crosstalk in a rat model of colitis. Methods: Adult female SD rats were divided into A) control, B) colitis, and C) colitis + minocycline groups. Experimental colitis was induced by administering 50% trinitrobenzene sulfonic acid into the distal colon in the colitis group and the minocycline group. Minocycline, a microglial inhibitor, was continuously infused into the intrathecal space in the minocycline group. The following investigations were performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2) nociceptive behavior observation induced by intravesical instillation of resiniferatoxin; (3) toluidine blue staining in the bladder; (4) Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord sections; and (5) quantitative RT-PCR to investigate interleukin-1β (IL-1β), chemokine ligand 3 (CCL3), and brain-derived neurotrophic factor (BDNF) gene expression in the L6 spinal cord. Results: In comparison with the control group, the colitis group showed significant increases in (1) micturition frequency during cystometry; (2) resiniferatoxin-induced freezing behavior (bladder pain); (3) the number of total and degranulated mast cells in the bladder; (4) the number of microglia in the L6 spinal cord, and (5) the expression of IL-1β, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover, intrathecal administration of minocycline alleviated these pathophysiological findings caused by experimental colitis. Conclusions: Spinal microglia may play an important role in colitis-induced bladder overactivity and enhanced bladder pain sensitivity in colitis rats.

Original languageEnglish
Pages (from-to)1320-1328
Number of pages9
JournalNeurourology and Urodynamics
Issue number4
Publication statusPublished - 2018 Apr


  • colitis model
  • interstitial cystitis
  • microglia
  • organ cross-sensitization
  • pelvic


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