Neuropathic Pain-Like Behavior after Brachial Plexus Avulsion in Mice: The Relevance of Kinin B 1 and B 2 Receptors

• Published in: The Journal of neuroscience Vol. 28; no. 11; pp. 2856 - 2863
• Main Authors: Quintão, Nara L. M., Passos, Giselle F., Medeiros, Rodrigo, Paszcuk, Ana F., Motta, Fabiana L., Pesquero, João B., Campos, Maria M., Calixto, João B.
• Format: Journal Article
• Language: English
• Published: 12-03-2008
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.4389-07.2008

The relevance of kinin B
1
(B
1
R) and B
2
(B
2
R) receptors in the brachial plexus avulsion (BPA) model was evaluated in mice, by means of genetic and pharmacological tools. BPA-induced hypernociception was absent in B
1
R, but not in B
2
R, knock-out mice. Local or intraperitoneal administration of the B
2
R antagonist Hoe 140 failed to affect BPA-induced mechanical hypernociception. Interestingly, local or intraperitoneal treatment with B
1
R antagonists, R-715 or SSR240612, dosed at the time of surgery, significantly reduced BPA-evoked mechanical hypernociception. Intrathecal or intracerebroventricular administration of these antagonists, at the surgery moment, did not prevent the hypernociception. Both antagonists, dosed by intraperitoneal or intrathecal routes (but not intracerebroventricularly) 4 d after the surgery, significantly inhibited the mechanical hypernociception. At 30 d after the BPA, only the intracerebroventricular treatment effectively reduced the hypernociception. A marked increase in B
1
R mRNA was observed in the hypothalamus, hippocampus, thalamus, and cortex at 4 d after BPA and only in the hypothalamus and cortex at 30 d. In the spinal cord, a slight increase in B
1
R mRNA expression was observed as early as at 2 d. Finally, an enhancement of B
1
R protein expression was found in all the analyzed brain structures at 4 and 30 d after the BPA, whereas in the spinal cord, this parameter was augmented only at 4 d. The data provide new evidence on the role of peripheral and central kinin B
1
R in the BPA model of neuropathic pain. Selective B
1
R antagonists might well represent valuable tools for the management of neuropathic pain.