NANC neurons

NO is also a likely candidate for the NANC messenger of the myenteric plexus of neurons in the gastrointestinal tract, which mediate peristaltic movements. These neurons are rich in NO synthase and inhibitors of this enzyme prevent the nerve-evoked relaxation of the gut [12]. Nitric oxide released from nitroprusside also stimulates ADP ribosylation of glyceradehyde 3-phosphate dehydrogenase [56]. Consequently, there may be a number of enzymes, which are probably Fe-centered, that may be activated by NO. 

It has been known for many years that autonomic effector tissues (eg, gut, airways, bladder) contain nerve fibers that do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Both motor and sensory NANC fibers are present. Although peptides are the most common transmitter substances found in these nerve endings, other substances, eg, nitric oxide synthase and purines, are also present in many nerve terminals (Table 6-1). Capsaicin, a neurotoxin derived from chili peppers, can cause the release of transmitter (especially substance P) from such neurons and, if given in high doses, destruction of the neuron. 

Besides neuropeptides, nitric oxide is an inflammatory mediator in the airways, which is also a vasodilator and a neurotransmitter. Nitric oxide is produced by the enzymatic action of nitric oxide synthetase on L-arginine. Airways contain this enzyme in three different forms, two of which termed neuronal and endothelial nitric oxide synthetase are constitutive whereas the third form called inducible nitric oxide synthetase is inducible. The inflammatory cytokines including IL-1 and TNF-a augment the expression of inducible nitric oxide synthetase in human airway epithelial cells. Nitric oxide causes bronchodilation as a result of the relaxation of bronchial smooth muscles. It has also been suggested that nitric oxide is the neurotransmitter of the inhibitory NANC bronchodilation. The detrimental effects of nitric oxide include airway inflammation and vasodilation. It causes airway edema by increasing the erudition of plasma due to increased blood flow to postcapillary venules. The increased blood flow may also contribute to an increased mucus secretion. The role of nitric oxide in inflammatory responses has not yet been established. 

In conclusion, the mentioned studies suggest that proinflammatory chemokines can either sensitize or desensitize receptor functions on or directly activate peripheral NANC nerves. This cross-(de)sensitization between neuronal (anti)pain and chemokine receptors or direct activation of NANC nerves may contribute to the development of visceral pain observed in inflammatory bowel disease and irritable bowel syndrome. 

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