抄録
It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. Here, we found that chronic pain caused a dramatic down-regulation of μ-opioid receptor function to activate its coupling with G-proteins of ventral tegmental area (VTA), and produced of the suppression of morphine-induced rewarding effect. Using the fluoro-gold (FG) microinjection into the VTA, numerous FG-labeled cells were detected in the lateral preoptic nucleus (LPO) and dorsolateral hypothalamus (DMH) of nerve-ligated rats. Subpopulations of β-endorphin-positive fibers in the LPO and DMH were co-labeled by FG. Furthermore, we found that chronic pain caused a dramatic down-regulation of cortical δ-opioid receptor function to activate its coupling with G-proteins, which is associated with the increased δ-opioid receptor phospholylation, and produced anxiety-like behaviors in mice, as characterized by both the light-dark and elevated plus-maze tests. These data provide direct evidence that the endogenous opioid-containing neuron projecting from the pain processing regions may be continuously activated by nerve ligation, resulting in the long-lasting down-regulation of μ- or δ-opioid receptors. This phenomenon may lead to the suppression of the morphine-induced rewarding effect and emotional disorders including aggravated anxiety under chronic pain-like state. [J Physiol Sci. 2006;56 Suppl:S50]
