1. 2013;16;65-76A Negative Correlation Between Hyperalgesia and Analgesia in Patients with Chronic Radicular Pain: Is Hydromorphone Therapy a Double-Edged Sword?
   Prospective Evaluation
   Erica Suzan, MSc, Elon Eisenberg, MD, Roi Treister, PhD, May Haddad, MSc, and Dorit Pud, PhD.

BACKGROUND: 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).

OBJECTIVES: 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.

STUDY DESIGN: Prospective evaluation

SETTING: Interdisciplinary Pain Clinic at a referral Health Care Campus

METHODS: 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.

RESULTS: 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).

LIMITATIONS: The nonrandomized, open-label, prospective evaluation.

CONCLUSION: 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.