The role of CNSNMDA receptors and nitric oxide in visceral hyperalgesia

被引:20
作者
Coutinho, SV [1 ]
Urban, MO [1 ]
Gebhart, GF [1 ]
机构
[1] Univ Iowa, Coll Med, Dept Pharmacol, Iowa City, IA 52242 USA
关键词
inflammation; colorectal distension; NMDA receptor; N-nitro-L-arginine methyl ester (L-NAME); rostral ventromedial medulla;
D O I
10.1016/S0014-2999(01)01331-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The studies summarized here document the role of NMDA receptors and nitric oxide in the lumbosacral spinal cord and rostral ventromedial medulla in the maintenance of visceral hyperalgesia. Experiments were conducted in rats in which drugs were administered into either the lumbosacral intrathecal space or directly into the rostral ventromedial medulla. The visceral stimulus was noxious colorectal distension, administered before and 3 h after intracolonic instillation of either saline or 25% zymosan. The visceromotor response to colonic distension was quantified and found to be significantly enhanced in rats in which the colon had previously been treated with zymosan. Enhanced responses to distension were attenuated dose-dependently by intrathecal administration of the NMA receptor channel blocker MK-801 and by inhibition of the neuronal isoform of nitric oxide synthase (nNOS). In corresponding studies wherein drugs were administered directly into the rostral ventromedial medulla, NMDA receptor antagonism and NOS inhibition dose-dependently attenuated exaggerated responses to colonic distension. Taken together, these data suggest that zymosan-produced visceral hyperalgesia is influenced both at the level of the spinal cord and rostral ventromedial medulla, and that descending facilitatory influences from the rostral ventromedial medulla are important to the maintenance of visceral hyperalgesia. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:319 / 325
页数:7
相关论文
共 41 条
[1]  
AANONSEN LM, 1987, J PHARMACOL EXP THER, V243, P9
[3]   EFFECTS OF INTRACOLONIC ACETIC-ACID ON RESPONSES TO COLORECTAL DISTENSION [J].
BURTON, MB ;
GEBHART, GF .
BRAIN RESEARCH, 1995, 672 (1-2) :77-82
[4]  
Coutinho S V, 2000, Prog Brain Res, V129, P375
[5]   A role for spinal nitric oxide in mediating visceral hyperalgesia in the rat [J].
Coutinho, SV ;
Gebhart, GF .
GASTROENTEROLOGY, 1999, 116 (06) :1399-1408
[6]   Role of glutamate receptors and nitric oxide in the rostral ventromedial medulla in visceral hyperalgesia [J].
Coutinho, SV ;
Urban, MO ;
Gebhart, GF .
PAIN, 1998, 78 (01) :59-69
[7]   Intracolonic zymosan produces visceral hyperalgesia in the rat that is mediated by spinal NMDA and non-NMDA receptors [J].
Coutinho, SV ;
Meller, ST ;
Gebhart, GF .
BRAIN RESEARCH, 1996, 736 (1-2) :7-15
[8]  
DIBIASI S, 1994, ANAT REC, V240, P131
[9]   ACTIVITY-DEPENDENT NEURONAL PLASTICITY FOLLOWING TISSUE-INJURY AND INFLAMMATION [J].
DUBNER, R ;
RUDA, MA .
TRENDS IN NEUROSCIENCES, 1992, 15 (03) :96-103
[10]  
FIELDS HL, 1994, TXB PAIN, P309