title: The concept of neurogenic inflammation.
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 alpha(1)-adrenoceptor antagonists used to treat lower urinary tract symptoms (LUTS). Indeed, the alpha(1)-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 alpha(1)-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.
authors.affiliation: Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence, Italy. pierangelo.geppetti@unifi.it
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
authors.forename: Romina
authors.initials: R
authors.lastname: Nassini
authors.forename: Serena
authors.initials: S
authors.lastname: Materazzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Benemei
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000473:pathology; D053448:Prostatism / Q000188:drug therapy* / Q000473:pathology; D011472:Prostatitis / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use*; D051381:Rats; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy / Q000473:pathology
chemical_list: D000317:Adrenergic alpha-Antagonists; D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D011799:Quinazolines; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; C047638:alfuzosin