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The bradykinin B 1 receptor antagonist BI 113823 reverses inflammatory hyperalgesia by desensitization of peripheral and spinal neurons
Author(s) -
Schuelert N.,
Just S.,
Corradini L.,
Kuelzer R.,
Bernloehr C.,
Doods H.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.573
Subject(s) - hyperalgesia , bradykinin , nociception , receptor , pharmacology , medicine , receptor antagonist , peripheral , antagonist , neuropeptide , freund's adjuvant , inflammation
Abstract Background Bradykinin is a neuropeptide released after tissue damage which plays an important role in inflammatory pain. The up‐regulation of the bradykinin B 1 receptor in response to inflammation makes it an attractive target for drug development. Aim was to investigate if the selective B 1 receptor antagonist BI 113823 reduces inflammation‐induced mechanical hyperalgesia and if the effect is mediated via peripheral and/or spinal B1 receptor antagonism. Methods Electrophysiological recordings of peripheral afferents and spinal neurons were combined with behavioural experiments to better understand the underlying mechanisms of B 1 receptor antagonism. Experiments were performed 24 h after injection of complete Freund's adjuvant ( CFA ) or saline into the paw of W istar rats. A gene expression analysis for the B 1 receptor was performed in different tissues. BI 113823 was administered orally or intrathecally to assess effects on CFA ‐induced hyperalgesia. Peripheral afferents of the saphenous nerve as well as spinal wide dynamic range ( WDR ) and nociceptive‐specific ( NS ) neurons were recorded, and mechanosensitivity was measured before and after BI 113823 administration. Results BI 113823 reduced CFA ‐induced mechanical hyperalgesia when administered orally or intrathecally. An increased B 1 receptor gene expression was found in peripheral and spinal neural tissue. BI 113823 significantly reduced mechanosensitivity of peripheral afferents and spinal NS neurons, but had no effect on WDR neurons. Conclusion The selective bradykinin B 1 receptor antagonist BI 113823 reduces CFA ‐induced mechanical hyperalgesia which is mediated via antagonism of peripheral as well as spinal bradykinin B 1 receptors. The selective modulation of CFA ‐sensitized spinal NS neurons by BI 113823 could be a promising property for the treatment of inflammatory pain.