Kinin B1 receptors contributes to acute pain following minor surgery in humans.
BACKGROUND
Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels.


RESULTS
Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor.


CONCLUSIONS
These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the early phase of inflammation and inflammatory pain. The up-regulation of B1 receptors may contribute to acute inflammatory pain through TRPV1 activation.
Hamza
May
M
NINR/NIH, 10 Center drive, Bethesda, MD 20892, USA.
Wang
Xiao-Min
XM
Adam
Albert
A
Brahim
Jaime S
JS
Rowan
Janet S
JS
Carmona
Gilberto N
GN
Dionne
Raymond A
RA
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001920:Bradykinin / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D020910:Ketorolac / Q000494:pharmacology; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D043782:Receptor, Bradykinin B2 / Q000235:genetics*; D050916:TRPV Cation Channels / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D001920:Bradykinin; D020910:Ketorolac