Macrophages in DRG participate in colitis- and stress-induced colonic mechanical hypersensitivity 4173

Abstract Description A number of factors are suggested to play critical roles in modulation of sensory neuron activity in dorsal root ganglia (DRG) thereby regulating colonic hypersensitivity and visceral pain. Macrophages are one of the nonneuronal cells that have low levels in DRG in healthy subjects, however, they expand in response to nerve injury or peripheral inflammation to participate in nerve regeneration, inflammatory pain, and mechanical allodynia. We use flow cytometry and RNAscope to show that macrophages marked by colony stimulating factor 1 receptor (Csf1R) are augmented in thoracolumbar DRG in water avoidance stress-induced colonic hypersensitivity in male mice, suggesting that macrophage expansion in DRG does not need to be organ-inflammation dependent. Csf1R+ macrophages are also present in DRG of human with inflammatory pain. Post 2,4,6-Trinitrobenzene sulfonic acid (TNBS)-induced colitis (day 7) and AP20187 treatment of MaFIA (macrophage FAS-induced apoptosis) male mice, the numbers of DRG Csf1R+ macrophages and DRG neurons expressing calcitonin gene-related peptide are reduced, simultaneously, colitis-induced colonic mechanical hypersensitivity is attenuated. Interestingly, AP treatment of MaFIA mice does not affect the amount of Csf1R+ components in the inflamed colon compared to AP vehicle control post TNBS treatment. These results suggest that Csf1R+ macrophages in DRG participate in the development of colonic pain, regardless of pain trigger from inflammation or stress. Funding Sources NIH R01 DK118137 NIH R01 DK 121131 Topic Categories Neuroimmunology (NEUR)