Up-regulation of ORL-1 receptors in spinal tissue of allodynic rats after sciatic nerve injury

• Published in: European journal of pharmacology Vol. 447; no. 1; pp. 59 - 65
• Main Authors: Briscini, Luca, Corradini, Laura, Ongini, Ennio, Bertorelli, Rosalia
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28-06-2002; Elsevier
• Subjects: Allodynia; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Animals; Biological and medical sciences; Constriction, Pathologic; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Ganglia, Spinal - metabolism; Injections, Spinal; Male; Medical sciences; Morphine - administration & dosage; Morphine - pharmacology; Nervous system (semeiology, syndromes); Neurology; Neuropathic pain; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nociceptin; Nociceptin Receptor; Nociceptin/orphanin FQ; Opioid Peptides - administration & dosage; Opioid Peptides - pharmacology; ORL1 receptor splice variant; Pain - metabolism; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Physical Stimulation; Protein Isoforms; Protein Precursors - biosynthesis; Protein Precursors - genetics; Rats; Rats, Sprague-Dawley; Receptors, Opioid - biosynthesis; Receptors, Opioid - genetics; Receptors, Opioid, mu - biosynthesis; Receptors, Opioid, mu - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Sciatic Nerve - pathology; Sciatic Neuropathy - metabolism; Spinal Cord - drug effects; Spinal Cord - metabolism; Up-Regulation; Allodynia; Nociceptin/orphanin FQ; Neuropathic pain; ORL1 receptor splice variant; Nociception; Nervous system diseases; Spinal cord; Pathophysiology; Rat; Treatment efficiency; Rodentia; Central nervous system; Peripheral neuropathy; Intrathecal administration; Nociceptin; Vertebrata; Chemotherapy; Mammalia; Analgesic; Pain; Treatment; N/OFQ receptor; Animal; Peripheral nerve disease; Mechanism of action; Sciatic nerve
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01833-2

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 μ-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.