First described over 100 years ago, the concept of opioid-induced hyperalgesia (OIH) suffuses nearly all aspects of pain management. OIH has gained prominence as a contributing factor for opioid tolerance and long-term treatment failure. The primary objective of this study was to delineate the effect of opioid dose and treatment duration on pain intensity and unpleasantness ratings following a standardized pain stimulus.

Among former heroin addicts in methadone maintenance programs, pain tolerance appears to be a more sensitive indicator of OIH than pain threshold, and cold pain a more reliable measure than electrical pain. The authors evaluated the effect of opioid dose and duration of therapy on a standardized, clinical pain stimulus--the subcutaneous administration of local anesthetic (LA) before an interventional pain management procedure.

Three hundred fifty-five patients scheduled for an interventional pain management procedure, plus 27 volunteers, without pain or analgesic therapy, underwent an identical standardized subcutaneous injection without a subsequent procedure. The standardized subcutaneous LA injection was performed using a 25-ga needle and 1 mL 1% lidocaine to raise a small skin wheal. Before injection, subjects were asked to rate their pain score using a 0-10 numeric pain rating scale. Immediately after the injection, subjects were asked to rate both their pain and their sensation of unpleasantness.

For those patients taking opioids, their regular dose was converted to oral morphine equivalents according to standard accepted guidelines. The oral morphine equivalents dose (MED) was then converted to a number on an escalating 6-point scale determined by a review of 100 medical records designed to stratify "high" and "low" dose opioid therapy for the authors' pain clinic.

A total of 282 patients participated in this study, including the controls. In addition to the 2 parameters above, other clinical and demographic data were collected for analysis, including age, sex, procedure, location of pain, procedure location, duration of pain, duration of opioid therapy, opioid regimen, and procedure numerical pain rating score.

The daily MED ranged or from 7.5 mg to over 3,000 mg among opioid therapy subjects. Subjects using intermediate or high doses of opioids (≥ 30 MED) were found to have higher preinjection pain scores than patients using no opioids. Excluding control subjects, neither the location of pain nor the injection location differed between treatment groups.

When only patients receiving opioids were considered, neither type (pain or unpleasantness) nor the location of the pain and unpleasantness of the injection was associated with any outcome variable. However, when data from all study subjects were analyzed, differences in pain and unpleasantness scores were noted for both type and location, where thoracic region injections were more likely to be perceived as painful or unpleasant than those in the pelvis.

Both mean postinjection pain intensity and unpleasantness scores were significantly higher in opioid therapy patients than in patients treated exclusively with the nonopioid analgesics, or in control subjects. These differences were independent of type of procedure, location of procedure, pain duration, pain location, and gender.

The results observed in this study are generally consistent with those demonstrated in previous studies involving heroin addicts in methadone maintenance programs and in surgical patients. These findings provide yet another piece of evidence supporting the possible presence of OIH in subjects using opioid therapy, and may complement the data generated using experimental pain conditions on this topic.