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.
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 colitisrats.