The concept of neurogenic inflammation

Authors

  • Pierangelo Geppetti,

    1. Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence and Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy
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  • Romina Nassini,

    1. Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence and Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy
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  • Serena Materazzi,

    1. Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence and Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy
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  • Silvia Benemei

    1. Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence and Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy
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Pierangelo Geppetti, Professor of Clinical Pharmacology, Department of Critical Care Medicine and Surgery, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
e-mail: pierangelo.geppetti@unifi.it

Abstract

Neurogenic inflammatory responses have recently been linked to both acute and chronic pathological conditions in the urinary tract. Neurogenic inflammation encompasses a series of vascular and non-vascular inflammatory responses, triggered by the activation of primary sensory neurons and the subsequent release of inflammatory neuropeptides, including substance P and calcitonin gene-related peptide. The reduction of neurogenic inflammatory responses may be key in the mode of action of the adrenergic α1-adrenoceptor antagonists used to treat lower urinary tract symptoms (LUTS). Indeed, the α1-adrenoceptor antagonist alfuzosin inhibits expression of the oncogene c-fos– a marker of nociceptive pathway activation – evoked by cyclophosphamide in rats.

Capsaicin ameliorates urinary bladder symptoms through its stimulatory action on the transient receptor potential vanilloid 1 (TRPV1) calcium channel, resulting in desensitization of bladder sensory nerve terminals. Involvement of the TRP cation channel, subfamily A, member 1 (TRPA1) has also been reported in models of neurogenic inflammation and nociception promoted by the cyclophosphamide metabolite, acrolein. Blockade by alfuzosin demonstrates the beneficial effects of α1-adrenoceptor antagonists on neurogenic inflammation via the transient receptor potential family of ionic channels. Consequently, these drugs may have an important role in reducing LUTS.

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