Author |
Ferreira, Juliano
![]() Beirith, Alessandra ![]() Mori, Marcelo A S ![]() ![]() Araujo, Ronaldo C. ![]() Bader, Michael ![]() Pesquero, Joao Bosco ![]() ![]() Calixto, Joao B ![]() |
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
allodynia hyperalgesia B-1 receptor kinin bradykinin |
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 |
Origin |
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Access rights | Open access ![]() |
Type | Article |
Web of Science ID | WOS:000227343800026 |
URI | http://repositorio.unifesp.br/handle/11600/28193 |
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