Fig. 1. A model of the neuroadaptive changes underlying expression and recovery of opioid-induced hyperalgesia (OIH) has been suggested by Celerier  et al . 37,Antinociceptive (  white bars ) and pronociceptive (  black bars ) systems are in balance at a low level of neuronal activity before the exposure to opioids. Pronociceptive systems become upregulated as a result of opioid exposure, which is reflected by the development of OIH. Upregulation of antinociceptive systems is associated with the discontinuation of opioid exposure, which results in the offset of OIH. However, recovery from OIH is the result of a new equilibrium between pronociceptive and antinociceptive systems that occurs at high level of neuronal activity. The high-level balance between pronociceptive and antinociceptive systems may be prone to derangements, which in a clinical context may build the basis for a long-term vulnerability to pain. From Celerier  et al. 37; used with permission, copyright 2001 by the Society for Neuroscience.