Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury.
Nociceptin, acting through the opioid receptor-like 1 (ORL1) receptor, produces anti-nociception in several models of neuropathy. We examined the involvement of the ORL1 receptor system in the allodynia developed after sciatic nerve ligation. Allodynic rats were selected by the von Frey hair and treated intrathecally with nociceptin or morphine. The peptide induced dose-dependent anti-allodynic activities, while morphine was effective at the higher dose only. By the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, the two described ORL1 receptor isoforms were up-regulated in the allodynic animals, but unmodified in non-allodynic rats. Both short and long ORL1 receptor mRNA isoforms increased in the ipsilateral lumbar enlargement (by 50% and 100%, respectively), while 50% and 60% increases were found in the ipsilateral L5-L6 dorsal root ganglia, respectively. No significant changes were observed for either the nociceptin precursor or mu-opioid receptor expression. Thus, the ORL1 receptor system seems to regulate the mechano-allodynia that developed after nerve damage, suggesting its potential role in the treatment of neuropathic pain.
Briscini
Luca
L
Schering-Plough Research Institute, San Raffaele Science Park, Via Olgettina, 58, 20132-, Milan, Italy.
Corradini
Laura
L
Ongini
Ennio
E
Bertorelli
Rosalia
R
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003251:Constriction, Pathologic; D005727:Ganglia, Spinal / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D010812:Physical Stimulation; D020033:Protein Isoforms; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000096:biosynthesis* / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000473:pathology*; D020426:Sciatic Neuropathy / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D009020:Morphine; D018847:Opioid Peptides; D020033:Protein Isoforms; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C121527:prepronociceptin; C000722285:Oprl1 protein, rat