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However, antinociceptive tolerance and dependence may develop with long\u2010term use of these drugs. It was found that \u03bc\u2010opioid receptors can interact with \u03b4\u2010opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking \u03b4\u2010opioid receptors. Recent studies have shown that \u03bc\u2010 and \u03b4\u2010opioid receptors are co\u2010expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of \u03bc\u2010opioid receptors with \u03b4\u2010opioid receptors in the nociceptive afferents is facilitated by the stimulus\u2010induced cell\u2010surface expression of \u03b4\u2010opioid receptors, and contributes to morphine tolerance. 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