Premium
Altered opioid‐mediated control of the spinal release of dynorphin and met‐enkephalin in polyarthritic rats
Author(s) -
Ballet Sébastien,
Mauborgne Annie,
Hamon Michel,
Cesselin François,
Collin Elisabeth
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/1098-2396(20000915)37:4<262::aid-syn3>3.0.co;2-6
Subject(s) - medicine , dynorphin , agonist , enkephalin , opioid , endocrinology , pharmacology , neurotransmission , opioid peptide , receptor
Previous studies showed that spinal opioidergic neurotransmission is markedly altered in the polyarthritic rat, a model of chronic inflammatory pain. Present investigations aimed at assessing possible changes in opioid‐mediated control of the spinal outflow of met‐enkephalin (ME) and dynorphin (DYN) in these animals. Intrathecal (i.t.) perfusion under halothane anesthesia showed that polyarthritis was associated with both a 40% decrease in the spinal outflow of ME‐like material (MELM) and a 90% increase in that of DYNLM. Local treatment with the μ‐opioid agonist DAGO (10 μM i.t.) inhibited equally (‐30%) the MELM outflow in polyarthritic and control rats, whereas the δ agonist DTLET (10 μM i.t.) also reduced the peptide outflow in controls (‐27%) but enhanced it in polyarthritic animals (+56%). On the other hand, both DAGO (10 μM i.t.) and DTLET (10 μM i.t.) decreased (‐40 and ‐49%) DYNLM outflow in polyarthritic rats, but were inactive in controls. Finally, neither MELM outflow nor that of DYNLM were affected by the κ‐agonist U50488H (10 μM i.t.) in both groups of rats. In all cases, the changes due to active agonists could be prevented by specific antagonists which were inactive on their own except the κ antagonist nor‐binaltorphimine (10 μM i.t.) that decreased (‐38%) DYNLM outflow in polyarthritic rats. These data indicate that functional changes in spinal opioid receptors may promote enkephalinergic neurotransmission and reduce dynorphinergic neurotransmission in polyarthritic rats, thereby contributing to the analgesic efficacy of opioids in inflammatory pain. Synapse 37:262–272, 2000. © 2000 Wiley‐Liss, Inc.