Regulation of two rat mas-related genes in a model of neuropathic pain.
The mas-related gene (Mrg) family is a large family of G-protein-coupled receptors which are variable in number depending on species. The so-called sensory-neuron-specific receptors (SNSRs) make up a subset of the Mrg family, and several of these have been implicated in nociceptive processes. To verify their specific localization in sensory ganglia, we have determined the expression patterns of two of them, rMrgA and rMrgC, in a panel of rat tissues. The quantitative PCR results in the rat tissue panel indicate that, while several non-neuronal tissues contain significant levels of mRNA for both receptors, these two receptors are most highly expressed in dorsal root ganglia and trigeminal ganglia. Given this, we have examined the effects of spinal nerve ligation (SNL) on the expression of these genes. Peripheral neuropathy induced by ligation of spinal nerves at L5 and L6 resulted in a pronounced mechanical allodynia. These behavioral changes in tactile sensitivity were accompanied by significant decreases (10- to 100-fold) in the mRNA expression of both rMrgA and rMrgC exclusively in the L5 and L6 dorsal root ganglia ipsilateral to the SNL. In situ hybridization studies demonstrated that this decrease did not result from neuronal loss but rather from a reduction in the hybridization signals for rMrgC over small-to-medium diameter L5 and L6 dorsal root ganglia neurons. While the functional implications of the altered regulation of rMrgA and rMrgC in neuropathic pain models remain unclear, the results suggest that therapeutics targeting these receptors may have limited utility.
Gustafson
Eric L
EL
Department of Discovery Technologies, Schering-Plough Research Institute, Kenilworth, NJ, USA. eric.gustafson@spcorp.com
Maguire
Maureen
M
Campanella
Marilena
M
Tarozzo
Glauco
G
Jia
Yuping
Y
Dong
Xiao-Wei
XW
Laverty
Maureen
M
Murgolo
Nicholas
N
Priestley
Tony
T
Reggiani
Angelo
A
Monsma
Frederick
F
Beltramo
Massimo
M
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000502:physiology*; D017403:In Situ Hybridization / Q000379:methods; D008026:Ligation / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D009475:Neurons, Afferent / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled