• David Z Yang, Billy Sin, Joshua Beckhusen, Dawei Xia, Rebecca Khaimova, and Ilia Iliev.
• Division of Pharmacy Practice, LIU Pharmacy (Arnold and Marie Schwartz College of Pharmacy), The Brooklyn Hospital Center, Brooklyn, NY.
• Am J Ther. 2019 May 1; 26 (3): e397-e405.

BackgroundOpioid-induced hyperalgesia (OIH) is a phenomenon that causes an increased pain sensitization and perception of pain to noxious stimuli secondary to opioid exposure. While this clinical effect has been described in the surgical setting, it is unclear if OIH occurs in the nonsurgical setting.Study QuestionTo review the available literature which evaluated OIH in nonsurgical settings.Data SourcesA comprehensive literature search was performed using PubMed (January 1946-July 2017) using a variety of keywords for OIH. This review included randomized controlled trials with objectives to identify OIH in the nonsurgical setting. The clinical outcomes of interest were identification of OIH, adverse events, and impact of OIH on opioid consumption.ResultsThe search identified 8 studies that fulfilled the criteria. Six studies enrolled healthy male volunteers, 1 study used chronic low-back patients, and another used heroin-dependent treatment-seeking adults. Studies used various opioids and dosages, including remifentanil, alfentanil, fentanyl, morphine, methadone, and buprenorphine. Three primary experimental pain induction models were used to evaluate for OIH. Measured outcomes included hyperalgesia area, pain threshold, and pain tolerance. All 5 studies that used the electrical stimulation model identified OIH as a significant outcome. However, only 2 of 5 studies using the cold pressor model and 1 of 3 studies using the heat pressor model identified OIH. None of the trials explored clinical outcomes, such as effects on opioid consumption.ConclusionsMost included studies identified OIH as a significant outcome within the nonsurgical setting. However, due to conflicting conclusions and various limitations, the clinical impact of OIH could not be assessed. Clinicians should monitor for effects of OIH in the nonoperative setting because there is insufficient evidence from the available literature to conclude that OIH is consistently observed in this setting.

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