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We also hypothesize that one type of cancer pain, the breakthrough pain, can be attributable to receptor-mediated interaction of opioids with tumor cells and intratumoral leukocytes. Surprisingly, long-term opioid treatment shares the same neuroinflammatory potential responsible for the chronicity of both cancer and non-cancer pain; thus, resulting in paradoxical worsening rather than relieving pain. This paradox has upset the world of pain therapy, with neuroinflammation now being a main target of emerging therapies.Protective ventila