Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia

Abstract

Background and objectives: This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia (OIH).

Methods: Twenty patients on long-term opioid therapy with suspected OIH were recruited along with 20 healthy controls. Pressure pain threshold, Pain50, a measure of intermediate suprathreshold pressure pain sensitivity, and tolerance levels were evaluated. As a secondary outcome, changes in pressure pain sensitivity after intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed.

Results: There were no significant differences in pain measures between healthy controls and patients. However, there was an association between higher doses of opioids and having a lower pain tolerance (r = -0.46, P = 0.041) and lower Pain50 (r = -0.46, P = 0.044), which was consistent with the hypothesis. Patients on more than 100 mg oral morphine equivalents displayed decreased pressure pain tolerance compared with patients taking less than 100 mg oral morphine equivalents (P = 0.042). In addition, male patients showed a hyperalgesic response to fentanyl administration, which was significant for the Pain50 measure (P = 0.002).

Conclusions: Whereas there were no differences between patients suspected of having OIH and the healthy controls, the finding that higher doses of opioids were associated with more sensitivity suggests that dose might be an important factor in the development of hyperalgesia. In addition, male patients demonstrated a hyperalgesic response after a bolus of fentanyl. Future studies are needed to develop better diagnostics for detecting hyperalgesia in the clinical setting.

Conflict of interest statement

Disclosures: Dr. Brummett receives research funding from Neuros Medical, Inc. (Willoughby Hills, OH) and is a consultant for Tonix Pharmaceuticals (New York, NY). Dr. Hassett has received research funding from and has been a consultant for Bristol-Myers Squibb (New York, NY) and Pfizer (New York, NY). Dr. Harte has received research funding from Cerephex (Palo Alto, CA), Forest Laboratories (New York, NY), and Merck (White House Station, NJ); and serves as a consultant for Pfizer (New York, NY), Analgesic Solutions (Natick, MA), Regeneron (Tarrytown, NY), and deCode Genetics (Reykjavik, Iceland). Dr. Harte is co-inventor of the MAST device used in this study. For the remaining authors, no potential conflicts were declared.

Figures

Figure 1. Relationship between baseline quantitative sensory testing (QST) outcomes and opioid dose

The relationship between the three baseline QST outcomes and the total opioid dose (oral morphine equivalents [OME]) in patients with suspected opioid induced hyperalgesia.

Figure 2. Baseline quantitative sensory testing results in healthy controls and patients

Patients were divided by dose to those with average daily dosing above and below 100mg oral morphine equivalents (OME). There were no differences between healthy controls and either patient group; however, the patients in the >100 mg OME were significantly more sensitive for tolerance and showed similar trends for threshold and Pain50. When observing all 3 groups, a pattern was observed to show patients 100 mg OME being more pain sensitive when compared to the healthy controls.

Figure 3. Change in quantitative sensory testing (QST) after the fentanyl challenge

The figure shows the changes in the 3 QST outcomes when subtracting the post-fentanyl challenge results from the post-placebo challenge. Male patients demonstrated a hyperalgesic response to the fentanyl challenge (change score