Alpha Blockers and neurogenic inflammation

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Thanks to Dr Shoskes for alerting me to this. This casts a new light on how alpha blockers may work.

BJU Int. 2008 Mar;101 Suppl 3:2-6.

The concept of neurogenic inflammation.

Geppetti P, Nassini R, Materazzi S, Benemei S.
Department of Critical Care Medicine and Surgery, Clinical Pharmacology Unit, University of Florence, Florence, Italy. [email protected]

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.

PMID: 18307678 [PubMed - indexed for MEDLINE]