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Pain Physician. 2013 Jan;16(1):65-76.

A negative correlation between hyperalgesia and analgesia in patients with chronic radicular pain: is hydromorphone therapy a double-edged sword?

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  • 1The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Institute of Pain Medicine, Rambam Health Care Campus, Haifa, Israel.



Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Yet, unconfirmed evidence suggests that chronic exposure to opioids may cause hypersensitivity to pain, a phenomenon known as opioid-induced hyperalgesia (OIH).


The current preliminary prospective study was aimed to explore the relationship between experimental OIH and clinical opioid induced analgesia (OIA) in a model of experimental OIH in patients with chronic radicular pain using intermediate-term opioid therapy.


Prospective evaluation


Interdisciplinary Pain Clinic at a referral Health Care Campus


Thirty patients with chronic neuropathic (radicular) pain were assessed prior to and following 4 weeks of an individually titrated dose of oral hydromorphone treatment (4-20 mg/d). The assessments included an evaluation of experimental OIH by testing for heat pain intensity and cold pain tolerance and an assessment of OIA by completing pain and disability questionnaires.


Hydromorphone was found to induce hyperalgesia, as measured by an elevation of phasic heat pain intensity (P < 0.05). At the same time, hydromorphone caused significant clinical analgesic effects. There was a notable reduction in average daily pain scores (primary analgesic outcome) of 26 Visual Analog Scale (0-100) points. A significant negative correlation was found between OIH and all OIA measures (r = -0.389, P < 0.05 for the primary analgesic outcome). Hydromorphone dosage was positively correlated with OIH (P < 0.01, r = 0.467) and negatively correlated with OIA parameters (r = -0.592, P < 0.01 for the primary analgesia outcome).


The nonrandomized, open-label, prospective evaluation.


A 4-week regimen of open-label hydromorphone therapy results in a dose-dependent OIH, which negatively correlates with its analgesic effect. Future randomized, controlled, and blinded studies are needed to verify these preliminary results. 

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