PAIN OUT: an international acute pain registry supporting clinicians in decision making and in quality improvement activities.

RATIONALE, AIMS AND OBJECTIVES: Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. METHODS: PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery. RESULTS: The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. CONCLUSION: PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

Investigating dose-dependent effects of placebo analgesia: a psychophysiological approach.

Investigating dose-dependent effects of placebo analgesia (PA) in laboratory subjects undergoing pain testing, we evaluated 2 hypotheses: (1) greater expectancy for relief produces greater PA, and (2) cued expectancy for relief triggered by a predictive cue leads to more enhanced analgesia than does passive expectancy (no predictive cue). We used conditioning procedures in which 84 subjects experienced reduced stimulation intensity following the application of purported analgesic creams to the 2 experimental fingers, while the control finger received the same levels of stimulation as in the baseline block. The dose of placebos was manipulated by creating 2 levels of expectations for relief. The form of expectation (cued vs uncued) was also manipulated by a predictive cue specifying the next finger to be stimulated. Subjective reports and psychophysiological responses served as critical indicators for evaluating impacts of the placebo manipulation on subsequent pain processing. The dose-dependent PA was unambiguously demonstrated by the predicted ordering of the 3 fingers (ie, manipulated expectation levels) in terms of both response sensitivity and average response magnitude, in mixed-effects analysis of 3 outcome indicators (evoked potential, skin conductance response, pain report). Greater expectation for relief led to both (1) greater reductions in the average dependent variable slope (response sensitivity) as a function of stimulus intensity, and (2) greater reductions in average response magnitude. Unexpectedly, uncued expectation led to a slightly larger PA than did cued expectation. The study provided clear evidence that PA can occur in a "dose"-dependent manner, mediated by the levels of expectancy for pain relief.

Toward validation of pain measurement tools for children: a pilot study.

We undertook to explore the validity of pain measurement tools for use in children in the postoperative period. The general approach was to determine the extent to which a measurement tool conformed with the clinical expectations about pain in the postoperative period; namely, that pain is low prior to surgery, increases following surgery, decreases with pain medication and decreases over time following surgery. In children aged 6 months to 3 years, we evaluated the CHEOPS and Observer pain scales. In children 3-6 years of age, we used the CHEOPS, Observer and Faces scale. In children 6-12 years of age, we studied the CHEOPS, Faces and visual analogue scales. In all instances, each of the scales conformed with the clinical expectations about pain following surgery. In addition, these scales were correlated with each other. Within the limitations of the measurement techniques used, these data provide support for the validity of the measurement tools evaluated.

Enhancement of morphine analgesia by fenfluramine in subjects receiving tailored opioid infusions.

We evaluated the ability of fenfluramine, a serotonin releaser, to increase the analgesic potency of morphine administered by tailored i.v. infusion. Ten normal volunteers participated in 4 test sessions, involving different treatments on different days: (1) oral placebo/saline infusion, (2) oral placebo/morphine infusion, (3) oral fenfluramine (60 mg)/saline infusion, and (4) oral fenfluramine/morphine infusion. Subjects experienced repetitive painful dental electrical stimuli at strong but tolerable intensities during testing. On the 2 test days involving morphine, the opioid was administered by a computer-pump system that used individual pharmacokinetic parameters to achieve consecutive, steady plasma concentrations near target values of 16, 32 and 64 ng morphine/ml; each morphine concentration plateau was maintained for 45 min. On the saline infusion days, our procedures were identical to morphine test days except that the infused fluid contained no drug. For all sessions outcome measures included subject ratings of pain intensity, dental evoked potential (EP) amplitude, and visual analog scale (VAS) ratings of subjective side-effect intensities (nausea, alertness, dizziness, itching, mood). We obtained these measures during baseline and at each morphine concentration plateau or at corresponding times during saline infusions. Fenfluramine significantly increased the analgesic potency of morphine during the opioid infusion, while fenfluramine alone produced borderline analgesic effects. Fenfluramine alone decreased alertness slightly, but did not significantly increase morphine side effects. Thus, we conclude that fenfluramine enhances the analgesic potency of morphine without a parallel increase in opioid side-effect potency.

Self-administration of morphine in bone marrow transplant patients reduces drug requirement.

Bone marrow transplant recipients were randomly assigned to receive morphine by either continuous infusion (32 patients) or self-administration of small boluses (patient-controlled analgesia (PCA), 26 patients) for control of chemoradiotherapy-induced oral mucositis pain. All patients received morphine for a minimum of 9 days and most required morphine for at least 14 days. Patients rated their pain and side-effect intensity daily using visual analogue scales. Patient pain ratings did not differ between the groups although PCA patients used only 53% as much morphine as the continuous infusion group. Tolerance did not develop in the PCA group; in patients receiving continuous infusion morphine dosage continued to increase throughout the study while pain scores remained constant, indicating that tolerance had developed. Nausea, alertness and respiratory rate measurements did not differ between groups. PCA appeared more effective than the hospital staff determined treatment at delivering the least amount of morphine required to produce maximal pain relief. Patients self-administering morphine did not appear to restrict morphine intake in order to minimize opioid side-effects.

Naloxone fails to reverse pain thresholds elevated by acupuncture: acupuncture analgesia reconsidered.

We were unable to demonstrate the reversal of dental acupunctural analgesia following the injection of 0.4 mg naloxone using evoked potential methodology. Since our findings differed from those of Mayer, Price and Rafii who used pain threshold methods, we attempted to replicate their study. Subjects who demonstrated acupunctural analgesia during electrical stimulation of the LI-4 point on the hands received either 1.2 mg naloxone or normal saline under double blind conditions. Pain thresholds elevated by acupuncture failed to reverse when naloxone was given. Review of experimental design issues, other related human subjects research, and animal studies on acupunctural analgesia provided little convincing evidence that endorphins play a significant role in acupunctural analgesia. Because endorphins can be released in response to a stressor, endorphin presence sometimes correlates with acupunctural treatment in animal studies and some human studies, especially those involving pain patients. The primary analgesia elicited by acupunctural stimulation seems to involve other mechanisms.

Comparative effects of acupuncture in Japan and the United States on dental pain perception.

The effect of low frequency electrical acupunctural stimulation on the perception of induced dental pain were compared in two cultural settings. Twenty Japanese and 20 American subjects (consisting of 10 Caucasians and 10 second or third generation Japanese) were tested in two functionally identical laboratories, one at Tottori University in Yonago, Japan and the other at the University of Washington. Each subject underwent a control and an acupuncture session on separate days wtih subjects counterbalanced for carry-over order effects. Sensory decision theory (SDT) analysis demonstrated a significant reduction in perceptual capability and an increased bias against reporting stimuli as painful following the acupuncture as treatment which was performed bilaterally at traditional facial points. No significant differences between groups in alteration of perceptual capability, bias or pain threshold were demonstrated, indicating that the cultural and racial differences studied did not influence responses to acupuncture in a laboratory setting.

Event-related potential correlates of analgesia; comparison of fentanyl, acupuncture, and nitrous oxide.

This study was undertaken to determine whether different analgesic treatments result in a common change in the event-related potentials (ERP) elicited during painful dental stimulation. The effects of electrical acupuncture delivered at 2 Hz to LI-4, the opiate fentanyl 0.1 mg i.v., and the inhalation analgesia mixture of 33% nitrous oxide in oxygen were examined in volunteers undergoing painful tooth pulp stimulation. ERPs were recorded at vertex and subjects provided reports of pain intensity. Discriminant function analysis was used to determine which subset of the pain report and ERP variables could best discriminate baseline from treatment conditions without regard to specificity of treatment. Together with pain report, amplitude of the ERP positive deflection at 250 msec was a significant indicator of analgesia across the 3 treatments. Other changes specific to the individual treatments were also observed. Since the 250 msec amplitude measure was not redundant statistically with pain report, the ERP data provided significant new information about analgesia even though pain report was a very sensitive measure. Pain report alone could account for 48% of the variance across treatments while ERP measures alone accounted for 34%.

On "the lateralization of pain".

The hypothesis put forth by Merskey and Watson [16] that pain, when lateralized, occurs more often on the left was tested in a sample of 264 patients seen at the University of Washington Pain Service. Contrary to the hypothesis, pain occurred with equal frequency on the left and the right. No differences were observed between patients with left and right lateralized pain on the MMPI, IBQ or Zung depression scales. The discrepancy between these findings and those of Merskey and Watson probably reflects differences in the populations studied, differences in the conventions used to define pain laterality, and the fact that the multiple statistical tests on a single sample used by Merskey and his colleagues lead to a large probability of obtaining spuriously significant results.

Evoked potential assessment of acupunctural analgesia: attempted reversal with naloxone.

The effects of electrical acupunctural stimulation (2 Hz) on pain judgments and evoked potentials are reported for two experiments using dental dolorimetry. In the first experiment subjects received acupuncture at points located in the same neurologic segment as the test tooth. In the second experiment subjects received acupuncture at points on the hands located on acupuncture meridians. In both instances acupuncture resulted in a reduction in pain intensity and smaller evoked potential amplitudes, but naloxone neither reversed the analgesia nor did it affect the evoked potentials. A pilot study was carried out to determine whether manual rather than electrical stimulation would produce an analgesia reversible by naloxone, but it failed to do so. These findings contribute to the growing evidence that acupunctural stimulation significantly reduces pain sensibility in volunteers undergoing dolorimetric testing, but they do not support the hypothesis that endorphin release is a mechanism by which acupuncture exerts analgesia.

Dental dolorimetry for human pain research: methods and apparatus.

Electrical stimulation of human tooth pulp provides a means of safely producing human pain in the laboratory. This paper describes a dolorimetry and data collection system for stimulating volunteers, recording responses and analyzing data. The system allows multilevel stimulation in pseudorandom sequences and analysis of results using the methods of Sensory Decision Theory. It consists of modified commercial equipment, specially designed circuitry, an interface, and a programmable calculator. Fundamental problems and safety considerations for electrical dental stimulation are reviewed. Reliability of stimulation and response measurement is discussed.

Brain evoked potentials are functional correlates of induced pain in man.

Electrical potentials evoked by 5 intensities of painful dental stimulation were recorded at the scalp. During testing, volunteers indicated subjective painfulness by verbal pain ratings and visual analogue scales. Evoked potentials (EPs) to each intensity, observed between 50 and 400 msec, were characterized by 4 waveform components. The peak-to-peak amplitudes, but not the peak latencies, of all 4 EP components systematically increased with increased stimulation. The amplitudes of the two earlier components correlated with stimulus intensity when the effect of subjective painfulness was controlled, but this was not the case for the later components. In contrast, the amplitudes of the two later components were associated with subjective painfulness but not with stimulus intensity. A strong linear relationship was observed between subjective painfulness and peak-to-peak amplitude for the EP component observed between 175 and 260 msec. The data suggest that the earlier EP components may reflect sensory transmission processes while the later components indicate brain activity when pain is perceived.

Illness behavior and depression compared in pain center and private practice patients.

Recent descriptions of illness behavior and personality factors in chronic pain patients reflect patient populations at clinics dealing with refractory, multiple referral pain problems. Pain patients from the University of Washington Pain Center were compared with patients from a private practice clinic with regard to illness behavior and depression. Private practice patients were significantly less depressed, showed less conviction of disease, general hypochondriasis, affect disturbance and were less somatically focussed than the Pain Center patients. Physicians in general practice treating pain patients should avoid forming stereotypes of chronic pain patients based on the experiences of referral clinics, for such characterizations may lead them to weigh psychologic factors too heavily in diagnosis.

Effects of doxepin on perception of laboratory-induced pain in man.

Beneficial effects have been observed in University of Washington Pain Clinic patients treated with tricyclic antidepressants, but such effects occur much earlier than predicted mood elevation. A laboratory investigation of pain perception was employed to test the hypothesis that doxepin, a tricyclic antidepressant, has analgesic properties. Healthy, normal volunteers were tested over a 4-week period during which they repeatedly performed Sensory Decision Theory tasks while undergoing painful dental stimulation. Doxepin and a placebo were administered after baseline measurement for 4 weeks under double blind conditions. No significant changes due to drug administration were observed in detection threshold or sensory sensitivity indices, but response bias against reporting the stimuli as painful changed dramatically after subjects began ingesting capsules. This effect was evident in both drug and placebo groups, and it was maintained across repeated weeks of testing. These observations suggest that the instructions given patients when the drug is administered have a profound effect on pain report.

Pain, depression, and illness behavior in a pain clinic population.

The relationship between depression, illness behavior and persistent pain was studied in 100 patients referred to the University of Washington Hospital Pain Clinic. The instruments used were the Illness Behavior Questionnaire (IBQ) and the Levine-Pilowsky Depression Questionnaire (LPD). To delineate those aspects of illness behavior characteristic of the Pain Clinic group, their scores were compared to those attained on the IBQ by a Family Medicine Clinic sample. The Pain Clinic group showed greater conviction of disease and somatic preoccupation than the comparison group. Further, they were reluctant to consider their health problems in psychologic terms, and denied current life problems. The Pain Clinic group's performance on the LPD indicated a low degree of depressive affect overall and few patients manifesting a depressive syndrome. The association between IBQ and depression scores suggests that the predominant clinical pattern presented by pain clinic patients is best characterized as a form of "abnormal illness behavior".