The effect of deletion of the orphan G-protein coupled receptor (GPCR) gene MrgE on pain-like behaviours in mice

被引:16
作者
Cox, Peter J. [1 ]
Pitcher, Tom [1 ]
Trim, Steven A. [1 ]
Bell, Christine H. [1 ]
Qin, Wenning [2 ]
Kinloch, Ross A. [1 ]
机构
[1] Pfizer Global Res & Dev, Discovery Biol, Pain Therapeut, Sandwich CT13 9NJ, Kent, England
[2] Pfizer Global Res & Dev, Genet Modified Models Ctr Emphasis, Groton, CT 06340 USA
关键词
D O I
10.1186/1744-8069-4-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The orphan GPCR MrgE is one of an extended family of GPCRs that are expressed in dorsal root ganglia (DRG). Based on these expression patterns it has been suggested that GPCRs like MrgE may play a role in nociception however, to date, no direct supporting evidence has emerged. We generated mutant mice lacking MrgE and examined the effects of deletion of this gene in three pain behavioural models. The effect of MrgE gene deletion on expression of Mrgs and genes involved in sensory neurone function was also investigated. Results: The absence of MrgE had no effect on the development of pain responses to a noxious chemical stimulus or an acute thermal stimulus. However, in contrast, the development but not the maintenance of neuropathic pain was affected by deletion of MrgE. The expression of Mrg genes was not significantly affected in the MrgE knockout (KO) mice with the sole exception of MrgF. In addition, the expression of 77 of 84 genes involved in sensory neuron development and function was also unaffected by deletion of MrgE. Of the 7 genes affected by MrgE deletion, 4 have previously been implicated in nociception. Conclusion: The data suggests that MrgE may play a role in selective pain behavioural responses in mice.
引用
收藏
页数:7
相关论文
共 21 条
[1]   The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways [J].
Akopian, AN ;
Souslova, V ;
England, S ;
Okuse, K ;
Ogata, N ;
Ure, J ;
Smith, A ;
Kerr, BJ ;
McMahon, SB ;
Boyce, S ;
Hill, R ;
Stanfa, LC ;
Dickenson, AH ;
Wood, JN .
NATURE NEUROSCIENCE, 1999, 2 (06) :541-548
[2]   The involvement of spinal bovine adrenal medulla 22-like peptide, the proenkephalin derivative, in modulation of nociceptive processing [J].
Cai, Meifang ;
Chen, Tingjun ;
Quirion, Remi ;
Hong, Yanguo .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2007, 26 (05) :1128-1138
[3]   Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain [J].
Chen, CL ;
Broom, DC ;
Liu, Y ;
de Nooij, JC ;
Li, Z ;
Cen, CA ;
Samad, OA ;
Jessell, TM ;
Woolf, CJ ;
Ma, QF .
NEURON, 2006, 49 (03) :365-377
[4]   Modulation of ion channels and synaptic transmission by a human sensory neuron-specific G-protein-coupled receptor, SNSR4/mrgX1, heterologously expressed in cultured rat neurons [J].
Chen, HM ;
Ikeda, SR .
JOURNAL OF NEUROSCIENCE, 2004, 24 (21) :5044-5053
[5]   MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal excitability [J].
Crozier, Robert A. ;
Ajit, Seena K. ;
Kaftan, Edward J. ;
Pausch, Mark H. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (16) :4492-4496
[6]   A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons [J].
Dong, XZ ;
Han, SK ;
Zylka, MJ ;
Simon, MI ;
Anderson, DJ .
CELL, 2001, 106 (05) :619-632
[7]   Detection of static and dynamic components of mechanical allodynia in rat models of neuropathic pain: are they signalled by distinct primary sensory neurones? [J].
Field, MJ ;
Bramwell, S ;
Hughes, J ;
Singh, L .
PAIN, 1999, 83 (02) :303-311
[8]   Recent advances in mammalian RFamide peptides: The discovery and functional analyses of PrRP, RFRPs and QRFP [J].
Fukusumi, Shoji ;
Fujii, Ryo ;
Hinuma, Shuji .
PEPTIDES, 2006, 27 (05) :1073-1086
[9]   Sensory central neuron-specific receptor activation elicits and peripheral nociceptive effects in rats [J].
Grazzini, E ;
Puma, C ;
Roy, MO ;
Yu, XH ;
O'Donnell, D ;
Schmidt, R ;
Dautrey, S ;
Ducharme, J ;
Perkins, M ;
Panetta, R ;
Laird, JMA ;
Ahmad, S ;
Lembo, PMC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (18) :7175-7180
[10]   Regulation of two rat mas-related genes in a model of neuropathic pain [J].
Gustafson, EL ;
Maguire, M ;
Campanella, M ;
Tarozzo, G ;
Jia, YP ;
Dong, XW ;
Laverty, M ;
Murgolo, N ;
Priestley, T ;
Reggiani, A ;
Monsma, F ;
Beltramo, M .
MOLECULAR BRAIN RESEARCH, 2005, 142 (01) :58-64