title: The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception.
abstract: The systemic administration of opioids can be used for their strong analgesic effect. However, extensive activation of opioid receptors (ORs) beyond the targeted tissue can cause dysphoria, pruritus, and constipation. Therefore, selective activation of peripheral ORs present in the afferent fibers of the targeted tissue can be considered a superior strategy in opioid analgesia to avoid potential adverse effects. The purpose of this study was to clarify the role of peripheral kappa opioid receptors (kORs) in arthritic pain for the possible use of peripheral ORs as a target in anti-nociceptive therapy. We administered U50488 or nor-BNI/DIPPA, a selective agonist or antagonist of kOR, respectively into arthritic rat knee joints induced using 1% carrageenan. After the injection of U50488 or U50488 with nor-BNI or DIPPA into the inflamed knee joint, we evaluated nociceptive behavior as indicated by reduced weight-bearing on the ipsilateral limbs of the rat and recorded the activity of mechanosensitive afferents (MSA). In the inflamed knee joint, the intra-articular application of 1μM, 10nM, or 0.1nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1μM and 10nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1μM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20μM nor-BNI or 10μM DIPPA significantly blocked the inhibitory effects of 1μM U50488 on nociceptive behavior and MSA activity in the inflamed knee joint. These results implicate that peripheral kORs can contribute to anti-nociceptive processing in an inflamed knee joint.
authors.affiliation: Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul 136-701, South Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Moon
authors.affiliation: Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul 136-701, South Korea.
authors.forename: Eui Ho
authors.initials: EH
authors.lastname: Park
authors.affiliation: Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul 136-701, South Korea.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Suh
authors.affiliation: Department of Orthopedic Surgery, Konkuk University School of Medicine, Chungju, South Korea.
authors.forename: Duk Hwan
authors.initials: DH
authors.lastname: Ko
authors.affiliation: Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul 136-701, South Korea.
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Department of Physiology, College of Medicine and Neuroscience Research Institute, Korea University, Seoul 136-701, South Korea. Electronic address: heehan@korea.ac.kr.
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Han
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000378:metabolism / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D007249:Inflammation; D007719:Knee Joint / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D059225:Nociception / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects; D010146:Pain; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
keywords: Carrageenan-induced arthritis; Peripheral kappa opioid receptor; Single nerve recording; U50488; Weight-bearing; nor-BNI/DIPPA