Implication of endogenous β-endorphin in the inhibition of the morphine-induced rewarding effect by the direct activation of spinal protein kinase C in mice

• Published in: Neuroscience letters Vol. 433; no. 1; pp. 54 - 58
• Main Authors: Niikura, Keiichi, Narita, Minoru, Okutsu, Daiki, Tsurukawa, Yuri, Nanjo, Kana, Kurahashi, Kana, Kobayashi, Yasuhisa, Suzuki, Tsutomu
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 05.03.2008; Elsevier
• Subjects: Analgesics; Animals; beta-Endorphin - genetics; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Enzyme Activation - genetics; Enzyme Activators - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hyperalgesia - chemically induced; Hyperalgesia - enzymology; Hyperalgesia - genetics; Injections, Spinal; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphine; Morphine - pharmacology; Morphine Dependence - enzymology; Morphine Dependence - genetics; Morphine Dependence - physiopathology; Narcotics - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - genetics; Neuropathic pain-like state; Neuropharmacology; Pain - enzymology; Pain - genetics; Pain - physiopathology; Pharmacology. Drug treatments; Protein kinase C; Protein Kinase C - metabolism; Reward; Spinal Cord - drug effects; Spinal Cord - enzymology; Vertebrates: nervous system and sense organs; β-Endorphin; Neuropathic pain-like state; Morphine; Protein kinase C; β-Endorphin; Enzyme; Transferases; Rodentia; Opiates; Narcotic analgesic; Neuropeptide; Opioid peptide; Vertebrata; Mammalia; Pain; Mouse; Animal
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.12.042

It has often been proposed that opioid addiction does not arise as a consequence of opioid treatment for pain. Recently, we demonstrated that activated protein kinase C (PKC) in the spinal cord associated with chronic pain-like hyperalgesia suppressed the morphine-induced rewarding effect in mice. In the present study, we investigated whether a gene deletion for an endogenous μ-opioid peptide β-endorphin could affect pain-like behavior and the suppression of the morphine-induced rewarding effect by the direct activation of PKC in the spinal cord. We found that activation of spinal PKC by intrathecal (i.t.) treatment with phorbol 12,13-dibutyrate (PDBu), a specific PKC activator, caused thermal hyperalgesia, pain-like behaviors and suppression of the morphine-induced rewarding effect. This suppression of morphine reward was eliminated in mice that lacked β-endorphin. In contrast, thermal hyperalgesia and pain-like behaviors were not affected in β-endorphin knockout mice. These results suggest that the activation of PKC in the spinal cord may play an essential role in the suppression of the morphine-induced rewarding effect in mice with neuropathic pain through the constant release of β-endorphin.