Neuropathic pain-like behavior after brachial plexus avulsion in mice: the relevance of kinin B1 and B2 receptors.
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.
Quintão
Nara L M
NL
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, CEP 88049-900, Florianópolis, Brazil. narafarmaco@yahoo.com.br
Passos
Giselle F
GF
Medeiros
Rodrigo
R
Paszcuk
Ana F
AF
Motta
Fabiana L
FL
Pesquero
João B
JB
Campos
Maria M
MM
Calixto
João B
JB
D000818:Animals; D001917:Brachial Plexus / Q000187:drug effects / Q000293:injuries* / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*
D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; C120984:R 715; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D001920:Bradykinin