Neuroimmune connections and regulation of function in the urinary bladder

Interactions between immune cells and neurons are increasingly implicated in normal and pathological processes in different organs and associated diseases. A cell that has emerged at the centre of these interactions is the mast cell, a cell more commonly recognized for its role in allergic reactions. Anatomical and functional associations are reviewed with respect to bladder function and the pathophysiology of a non-infectious painful bladder condition, interstitial cystitis. The availability of bladder biopsies has provided the unique opportunity to investigate these interactions in humans. Moreover, the existence of overlapping syndromes, such as irritable bowel syndrome, has shown that the underlying mechanisms involving mucosal permeability and sensory neuron activation depend on neuropeptide activation of mast cells. In vitro evidence is presented for anatomical and functional interactions between mucosal-like mast cells and neuron-like pheochromocytoma cells. Stress affects the mast cell-neuronal interactions by release of corticotropin-releasing hormone or the related peptide urocortin (directly, and via neurotensin and substance P), which lead to mast cell activation. Cytokines released from mast cells may then further activate the stress response. Interruption of stress-induced mast cell activation may offer new therapeutic alternatives.