Reduced nerve injury-induced neuropathic pain in kinin B-1 receptor knock-out mice

Reduced nerve injury-induced neuropathic pain in kinin B-1 receptor knock-out mice

Author Ferreira, Juliano Google Scholar
Beirith, Alessandra Google Scholar
Mori, Marcelo A S Autor UNIFESP Google Scholar
Araujo, Ronaldo C. Google Scholar
Bader, Michael Google Scholar
Pesquero, Joao Bosco Autor UNIFESP Google Scholar
Calixto, Joao B Google Scholar
Institution Universidade Federal de Santa Catarina (UFSC)
Universidade Federal de São Paulo (UNIFESP)
Univ Mogi Cruzes
Max Delbruck Ctr Mol Med
Abstract Injury to peripheral nerves often results in a persistent neuropathic pain condition that is characterized by spontaneous pain, allodynia, and hyperalgesia. Nerve injury is accompanied by a local inflammatory reaction in which nerve-associated and immune cells release several pronociceptive mediators. Kinin B-1 receptors are rarely expressed in nontraumatized tissues, but they can be expressed after tissue injury. Because B-1 receptors mediate chronic inflammatory painful processes, we studied their participation in neuropathic pain using receptor gene-deleted mice. in the absence of neuropathy, we found no difference in the paw-withdrawal responses to thermal or mechanical stimulation between B-1 receptor knock-out mice and 129/J wild-type mice. Partial ligation of the sciatic nerve in the wild-type mouse produced a profound and long-lasting decrease in thermal and mechanical thresholds in the paw ipsilateral to nerve lesion. Threshold changed neither in the sham-operated animals nor in the paw contralateral to lesion. Ablation of the gene for the B-1 receptor resulted in a significant reduction in early stages of mechanical allodynia and thermal hyperalgesia. Furthermore, systemic treatment with the B-1 selective receptor antagonist des-Arg(9)-[Leu(8)]-bradykinin reduced the established mechanical allodynia observed 7-28d after nerve lesion in wild-type mice. Partial sciatic nerve ligation induced an upregulation in B-1 receptor mRNA in ipsilateral paw, sciatic nerve, and spinal cord of wild-type mice. Together, kinin B-1 receptor activation seems to be essential to neuropathic pain development, suggesting that an oral-selective B-1 receptor antagonist might have therapeutic potential in the management of chronic pain.
Keywords neuropathic pain
B-1 receptor
Language English
Date 2005-03-02
Published in Journal of Neuroscience. Washington: Soc Neuroscience, v. 25, n. 9, p. 2405-2412, 2005.
ISSN 0270-6474 (Sherpa/Romeo, impact factor)
Publisher Soc Neuroscience
Extent 2405-2412
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000227343800026

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