Antihyperalgesic effects of vanilloid-1 and bradykinin-1 receptor antagonists following spinal cord injury in rats.
OBJECTIVE
The authors previously discovered that genes for the bradykinin-1 (B1) receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des-Arg9,Leu8]-bradykinin) antagonists on TH in animals following SCI.


METHODS
The rats were subjected to contusion SCI and then divided into groups in which TH did or did not develop. The animals from both groups were given either AMG9810, Lys-(Des-Arg9,Leu8)-bradykinin, or the drug-specific vehicle (control groups). Animals were tested for TH preinjury and at regular intervals after SCI by using the hindlimb withdrawal latency test.


CONCLUSIONS
The administration of AMG9810 likely improves TH as a result of a generalized analgesic effect, whereas the effect of Lys-(Des-Arg9,Leu8)-bradykinin appears more specific to the reversal of TH. This information has potential usefulness in the development of treatment strategies for post-SCI neuropathic pain.
Rajpal
Sharad
S
Department of Neurological Surgery, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
Gerovac
Tiffany A
TA
Turner
Nicholas A
NA
Tilghman
Jessica I
JI
Allcock
Bradley K
BK
McChesney
Shannon L
SL
Miranpuri
Gurwattan S
GS
Park
Seung W
SW
Resnick
Daniel K
DK
D000178:Acrylamides / Q000494:pharmacology*; D000818:Animals; D065168:Bradykinin Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007609:Kallidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000150:complications*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D065168:Bradykinin Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D007609:Kallidin; C052787:kallidin, des-Arg(10)-