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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

2008; Elsevier BV; Volume: 433; Issue: 1 Linguagem: Inglês

10.1016/j.neulet.2007.12.042

1872-7972

Keiichi Niikura, Minoru Narita, Daiki Okutsu, Yuri Tsurukawa, Kana Nanjo, Kana Kurahashi, Yasuhisa Kobayashi, Tsutomu Suzuki,

Pharmacological Effects of Natural Compounds

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 mu-opioid peptide beta-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 beta-endorphin. In contrast, thermal hyperalgesia and pain-like behaviors were not affected in beta-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 beta-endorphin.