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Presence of a reduced opioid response in interleukin‐6 knock out mice
Author(s) -
Bianchi Mauro,
Maggi Roberto,
Pimpinelli Federica,
Rubino Tiziana,
Parolaro Daniela,
Poli Valeria,
Ciliberto Gennaro,
Panerai Alberto E.,
Sacerdote Paola
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00563.x
Subject(s) - opioid , receptor , endogenous opioid , nociception , morphine , endocrinology , medicine , opioid peptide , endogeny , beta endorphin , opioid receptor , pharmacology , chemistry
Cytokines are known to influence neuronal functions. The purpose of this study was to investigate the putative role of the cytokine interleukin‐6 (IL‐6) in the pathways involved in opioid‐mediated responses, by using IL‐6‐deficient mice. We reported that with a thermal stimulus IL‐6‐knock‐out (IL‐6KO) mice presented nociceptive thresholds similar to those measured in their controls. However, they showed a reduced analgesic response both to the restraint stress and to the administration of low doses of morphine. Hypothalamic levels of the opioid peptide β‐endorphin were significantly higher in IL‐6KO mice than they were in their controls. The development of tolerance to the analgesic effect of morphine was more rapid in IL‐6‐deficient mice than in wild‐type controls. Binding experiments showed that the number of opioid receptors in the midbrain, but not in the hypothalamus, decreased in IL‐6KO mice. Autoradiographic binding analysis revealed that the density of μ receptors diminished while the δ‐opioid receptors did not. These results suggest that IL‐6 is necessary for a correct development of neuronal mechanisms involved in the response to both endogenous and exogenous opiates.