Gene expression profiling of melanocortin system in neuropathic rats supports a role in nociception.
The melanocortin (MC) system is involved in several biological functions. Its possible role in nociception has recently attracted attention in the field. Published data suggest that melanocortin antagonists are analgesic and agonists are hyperalgesic. Gene expression information about the MC system components (receptor, agonist and antagonist) in pain relevant areas is at present limited. To deepen our knowledge, we studied the expression of MC system components in nai;ve, sham and neuropathic rat spinal cord and dorsal root ganglia (DRG) by PCR and quantitative real-time PCR. MC4 receptor, proopiomelanocortin (POMC) and agouti-related protein (AgRP) transcripts were detected in both spinal cord and DRG, whereas MC3 receptor was detected only in the spinal cord. To study the relationship between the MC system and chronic pain, we used the chronic constriction injury model and gene expression analysis was performed in rats showing both tactile allodynia and thermal hyperalgesia. MC4 and POMC transcript were upregulated in the spinal cord of neuropathic rats, whereas MC3 and AgRP expression were unaffected. Thus, this study demonstrates for the first time the presence of AgRP in the spinal cord and DRG, suggesting that it could play a role in the regulation of MC system activity. In addition, the upregulation of POMC and MC4, in parallel with the presence of tactile allodynia and thermal hyperalgesia, further supports the idea of MC system involvement in nociception.
Beltramo
Massimiliano
M
Schering-Plough Research Institute, San Raffaele Biomedical Science Park, Via Olgettina 58, 20132 Milan, Italy. massimiliano.beltramo@spcorp.com
Campanella
Marilena
M
Tarozzo
Glauco
G
Fredduzzi
Silva
S
Corradini
Laura
L
Forlani
Angelo
A
Bertorelli
Rosalia
R
Reggiani
Angelo
A
D054369:Agouti-Related Protein; D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D000521:alpha-MSH / Q000378:metabolism*
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C470053:Mc3r protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin