Neurogenic inflammation and its involvement in uterine cervical ripening

Neurogenic inflammation involves primary afferent nerve fibers that release the transmitters, substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP) and possibly nitric oxide (NO), from their peripheral terminals. These transmitters bind to receptors to (1) induce vasodilation, (2) Increase postcapillary venule permeability allowing migration of inflammatory immune cells - monocytes (which transform into macrophages) and neutrophils - into the tissue, and (3) activate mast cells. SP degranulates mast cells releasing histamine, interleukins, and granulocyte macrophage-colony stimulating factor. Uterine cervical ripening involves tissue remodeling and may occur, in part, through a local inflammatory process. Preliminary evidence suggests that uterine innervation influences cervical ripening at parturition through release of transmitters that participate in neurogenic inflammation. Studies were undertaken in pregnant and parturient rats to determine (1) anatomical associations of nerve fibers containing SP, NKA, CGRP, and NO labeled nerve fibers with cervical venules, (2) if SP nerve fibers were located adjacent to mast cells, (3) if the tachykinin receptor is present in cervical venules, and (4) if there are changes in inflammatory cell concentration in the cervical stroma. In addition, monastral blue was used to reveal the location of venules that showed protein extravasation and in situ hybridization was used to demonstrate neurokinin-1 receptor mRNA expression in cervical venules. The results indicate that all the elements for neurogenic inflammations are present in the pregnant and parturient rat cervix. They include peripheral primary afferent nerve terminals containing SP, NKA, CGRP, and NO, the presence of the neurokinin-1 receptor, inflammatory immune cells (neutrophils, epsinophils, and mast cells), and postcapillary venule permeability.