TY - JOUR
T1 - The contribution of activated peripheral kappa opioid receptors (kORs) in the inflamed knee joint to anti-nociception
AU - Moon, Sun Wook
AU - Park, Eui Ho
AU - Suh, Hye Rim
AU - Ko, Duk Hwan
AU - Kim, Yang In
AU - Han, Hee Chul
N1 - Funding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (grant number 2010-0013485 ) and the Brain Korea 21 Project (Grant no. F16SN23D2101 ), and partially supported by Chung Yang, Cha Young Sun, M. D. and Jang Hi Joo Yeu Sa Memorial Fund (Grant no. 2014-R-01 ).
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 1 μM, 10 nM, or 0.1 nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1 μM and 10 nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1 μM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20 μM nor-BNI or 10 μM DIPPA significantly blocked the inhibitory effects of 1 μM 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.
AB - 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 1 μM, 10 nM, or 0.1 nM U50488 resulted in a significant reduction in nociceptive behavior. In addition, 1 μM and 10 nM U50488 decreased MSA activity. However, in a non-inflamed knee joint, 1 μM U50488 had no effect on MSA activity. Additionally, intra-articular pretreatment with 20 μM nor-BNI or 10 μM DIPPA significantly blocked the inhibitory effects of 1 μM 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.
KW - Carrageenan-induced arthritis
KW - Peripheral kappa opioid receptor
KW - Single nerve recording
KW - U50488
KW - Weight-bearing
KW - nor-BNI/DIPPA
UR - http://www.scopus.com/inward/record.url?scp=84978818299&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2016.06.048
DO - 10.1016/j.brainres.2016.06.048
M3 - Article
C2 - 27378583
AN - SCOPUS:84978818299
VL - 1648
SP - 11
EP - 18
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -