Role of kinin B1 and B2 receptors in a rat model of neuropathic pain.
Kinin B1 and B2 receptor (R) gene expression (mRNA) is increased in the sensory system after peripheral nerve injury. This study measured the densities of B1R and B2R binding sites in the spinal cord and dorsal root ganglia (DRG) by quantitative autoradiography, and evaluated the effects of two selective non-peptide antagonists at B1R (LF22-0542) and B2R (LF16-0687) on pain behavior after partial ligation of the left sciatic nerve. Increases of B1R binding sites were seen in superficial laminae of the ipsi- and contralateral spinal cord at 2 and 14 days while B2R binding sites were increased on the ipsilateral side at 2 days and on both sides at 14 days. In DRG, B1R and B2R binding sites were significantly increased at 2 days (ipsilateral) and 14 days on both sides. Whereas tactile allodynia started to develop progressively from 2 to 25 days post-ligation, the occurrence of cold allodynia and thermal hyperalgesia became significant from day 8 and day 14 post-ligation, respectively. At day 21 after sciatic nerve ligation, thermal hyperalgesia was blocked by LF22-0542 (10 mg/kg, s.c.) and LF16-0687 (3 mg/kg, s.c.), yet both antagonists had no effect on tactile and cold allodynia. Data highlight the implication of both kinin receptors in thermal hyperalgesia but not in tactile and cold allodynia associated with peripheral nerve injury. Hence LF22-0542 and LF16-0687 present therapeutic potential for the treatment of some aspects of neuropathic pain.
Petcu
M
M
Département de Physiologie, Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
Dias
J P
JP
Ongali
B
B
Thibault
G
G
Neugebauer
W
W
Couture
R
R
D000178:Acrylamides / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D005650:Fumarates / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology*; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000502:physiology*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*
D000178:Acrylamides; D005650:Fumarates; C403051:LF 16-0687; C512396:N-((4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)methyl)-2-(2-(((4-methoxy-2,6-dimethylphenyl) sulfonyl)methylamino)ethoxy)-N-methylacetamide, fumarate; D011804:Quinolines; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2