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Reg Anesth Pain Med. Author manuscript; available in PMC 2016 November 01. Published in final edited form as: Reg Anesth Pain Med. 2015 ; 40(6): 687–693. doi:10.1097/AAP.0000000000000315.

Pressure Pain Sensitivity in Patients With Suspected OpioidInduced Hyperalgesia

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Ronald A. Wasserman, MD, Afton L. Hassett, PsyD, Steven E. Harte, PhD, Jenna Goesling, PhD, Herbert L. Malinoff, MD, Daniel W. Berland, MD, Jennifer Zollars, BA, Stephanie E. Moser, PhD, and Chad M. Brummett, MD Division of Pain Research and the Back and Pain Center, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan

Abstract Background and Objectives—This study was designed to test whether a brief quantitative sensory testing (QST) assessment could be used to detect hyperalgesia in patients with suspected opioid-induced hyperalgesia. Methods—Twenty patients on long-term opioid therapy with suspected opioid-induced hyperalgesia were recruited along with and 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 following intravenous administration of placebo (saline) and fentanyl (1.5 μg/kg) were assessed.

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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 >100 mg oral morphine equivalents (OME) displayed decreased pressure pain tolerance compared to patients taking 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.

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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 < 0) when compared with healthy males and female patients.

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Table 1

Baseline descriptive data

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Healthy Controls

Patients

N = 20

N = 20

P-value

Demographics Age

29.2 (13.2)

44.5 (9.2)

< 0.001

Sex (% Male)

50%

35%

0.337

Race (% Caucasian)

61%

95%

0.022

Pain Severity (BPI)

0.1 (0.2)

6.2 (1.3)

< 0.001

Neuropathic pain (PainDETECT)

0.3 (1.0)

19.7 (7.4)

< 0.001

Fibromyalgia Survey Score

1.1 (1.2)

14.2 (7.6)

< 0.001

Catastrophizing

1.5 (2.7)

17.8 (8.4)

< 0.001

Depressive symptoms (HADS)

0.9 (1.1)

9.2 (3.8)

< 0.001

Pain Phenotype

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Anxiety symptoms (HADS)

1.5 (1.7)

9.4 (3.7)

< 0.001

Fatigue (PROMIS)

10.1 (1.0)

24.3 (5.2)

< 0.001

Sleep (PROMIS)

12.3 (3.0)

33.3 (5.7)

< 0.001

The patient group was significantly older and had a higher percentage of Caucasians. As expected, the patient group also reported a significantly worse pain phenotype. Note: Means and standard deviations are presented for continuous variables, and percentages are presented for dichotomous variables. Mean differences assessed using t-test, and percent differences were assessed using the chi-square test. BPI = Brief Pain Inventory; HADS = Hospital Anxiety and Depression Scale; PROMIS = Patient Reported Outcomes Measurement Information System.

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Table 2

Quantitative Sensory Testing Results

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There were no differences detected in the mean (standard deviation) quantitative sensory testing (QST) results between suspected opioid-induced hyperalgesia (OIH) patients and healthy controls. Healthy

Patients

N = 20*

N = 20

P-value

Threshold

3.0 (1.2)

2.7 (1.4)

0.432

Pain50

5.3 (1.4)

5.7 (1.5)

0.489

Tolerance

6.1 (1.2)

6.5 (1.6)

0.353

Threshold

2.6 (1.1)

2.9 (1.5)

0.499

Pain50

4.9 (1.7)

5.7 (1.7)

0.130

Tolerance

5.8 (1.7)

6.6 (1.8)

0.173

Threshold

3.0 (1.3)

3.6 (1.9)

0.328

Pain50

5.6 (2.0)

6.0 (2.0)

0.589

Tolerance

6.4 (1.9)

6.9 (2.0)

0.422

Baseline QST

Post-placebo QST

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Post-fentanyl QST

All quantitative sensory testing (QST) values listed are kg/cm2. *

Note that 2 healthy participants do not have data included for placebo & fentanyl QST.

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Table 3

Baseline Tolerance, Threshold, and Pain50 controlling for age and gender

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In this multivariate linear regression model controlling for age and sex, there were no differences between healthy controls and patients for measures of evoked pain. Threshold Coefficient

SE

P-value

Participant type

0.37

0.47

0.439

Age

-0.05

0.02

0.012

Sex

-0.11

0.39

0.786

Intercept

4.41

0.61

Pressure Pain Sensitivity in Patients With Suspected Opioid-Induced Hyperalgesia.

This study was designed to test whether a brief quantitative sensory testing assessment could be used to detect hyperalgesia in patients with suspecte...
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