Operant conditioning of enhanced pain sensitivity by heat-pain titration

Operant conditioning mechanisms have been demonstrated to be important in the development of chronic pain. Most experimental studies have investigated the operant modulation of verbal pain reports with extrinsic reinforcement, such as verbal reinforcement. Whether this reflects actual changes in the subjective experience of the nociceptive stimulus remained unclear. This study replicates and extends our previous demonstration that enhanced pain sensitivity to prolonged heat-pain stimulation could be learned in healthy participants through intrinsic reinforcement (contingent changes in nociceptive input) independent of verbal pain reports. In addition, we examine whether different magnitudes of reinforcement differentially enhance pain sensitivity using an operant heat-pain titration paradigm. It is based on the previously developed non-verbal behavioral discrimination task for the assessment of sensitization, which uses discriminative down- or up-regulation of stimulus temperatures in response to changes in subjective intensity. In operant heat-pain titration, this discriminative behavior and not verbal pain report was contingently reinforced or punished by acute decreases or increases in heat-pain intensity. The magnitude of reinforcement was varied between three groups: low (N1=13), medium (N2=11) and high reinforcement (N3=12). Continuous reinforcement was applied to acquire and train the operant behavior, followed by partial reinforcement to analyze the underlying learning mechanisms. Results demonstrated that sensitization to prolonged heat-pain stimulation was enhanced by operant learning within 1h. The extent of sensitization was directly dependent on the received magnitude of reinforcement. Thus, operant learning mechanisms based on intrinsic reinforcement may provide an explanation for the gradual development of sustained hypersensitivity during pain that is becoming chronic.     

Efficacy of dronabinol as an adjuvant treatment for chronic pain patients on opioid therapy.

We assessed the efficacy of dronabinol (Marinol capsules; Solvay Pharmaceuticals, Brussels, Belgium), a synthetic Delta(9)-THC (tetrahydrocannabinol), in 30 patients taking opioids for chronic pain to determine its potential analgesic effects as an adjuvant treatment. Phase I of this 2-phase study was a randomized, single-dose, double-blinded, placebo-controlled, crossover trial in which subjects were randomly administered either 10 mg or 20 mg of dronabinol or identical placebo capsules over the course of three, 8-hour visits. Baseline self-report measures, hourly ratings of pain intensity, pain relief, pain bothersomeness, treatment satisfaction, mood, side effects, and blood serum levels were obtained. Phase II was an extended open-label titrated trial of dronabinol as add-on medication to patients on stable doses of opioids. Results of the Phase I study showed that patients who received dronabinol experienced decreased pain intensity and increased satisfaction compared with placebo. No differences in benefit were found between the 20 mg and 10 mg doses. In the Phase II trial, titrated dronabinol contributed to significant relief of pain, reduced pain bothersomeness, and increased satisfaction compared with baseline. The incidence of side effects was dose-related. Overall, the use of dronabinol was found to result in additional analgesia among patients taking opioids for chronic noncancer pain. PERSPECTIVE: This study examines the effect of adding a cannabinoid to the regimen of patients with chronic pain who report significant pain despite taking stable doses of opioids. The results of our preliminary study suggest that dronabinol, a synthetic THC, may have an additive effect on pain relief.     

Environmental and interoceptive influences on chronic low back pain behavior

The operant conditioning theory states that environmental stimuli greatly influence chronic pain behavior. In contrast, the hypochondriasis theory states that pain behavior is the result of an intensified pain perception which is part of a more general augmentation and amplification of normal bodily sensations. The operant theory predicts that pain behavior (operationalized as poorer endurance on the part of chronic low back pain patients as compared to the endurance of control subjects in a series of 6 working-to-tolerance treadmill tests) will decrease when no verbal or non-verbal feedback for treadmilling behavior is given. This hypothesis could not be confirmed in the present study. The hypochondriasis theory predicts that chronic pain patients will report more bodily sensations, both at rest and after treadmill exercises. This hypothesis was strongly supported by the findings of the present study.     

Retarded disengagement from pain cues: the effects of pain catastrophizing and pain expectancy

The role of operant conditioning for the development and maintenance of chronic pain was examined in 30 chronic back pain patients (CBP) and 30 matched healthy controls. Half of each group was reinforced for increased, half for decreased pain reports while EEG, EOG, heart rate, skin conductance and muscle tension levels were recorded. Both groups showed similar learning rates, however, the CBP patients displayed slower extinction of both the verbal and the cortical (N150) pain response. In addition, the CBP group displayed prolonged elevated electromyogram levels to the task. These data suggest that CBP patients are more easily influenced by operant conditioning factors than healthy controls and this susceptibility may add to the maintenance of the chronic pain problem.     

The effects of slow breathing on affective responses to pain stimuli: An experimental study

This study examined whether breathing rate affected self-reported pain and emotion following thermal pain stimuli in women with fibromyalgia syndrome (FM: n = 27) or age-matched healthy control women (HC: n = 25). FM and HC were exposed to low and moderate thermal pain pulses during paced breathing at their normal rate and one-half their normal rate. Thermal pain pulses were presented in four blocks of four trials. Each block included exposure to both mild and moderate pain trials, and periods of both normal and slow paced breathing. Pain intensity and unpleasantness were recorded immediately following each pain trial, and positive and negative affect were assessed at the end of each block of trials. Compared to normal breathing, slow breathing reduced ratings of pain intensity and unpleasantness, particularly for moderately versus mildly painful thermal stimuli. The effects of slow breathing on pain ratings were less reliable for FM patients than for HCs. Slow versus normal breathing decreased negative affect ratings following thermal pain pulses for both groups, and increased positive affect reports, but only for healthy controls with high trait negative affect. Participants who reported higher levels of trait positive affect prior to the experiment showed greater decreases in negative affect as a result of slow versus normal breathing. These experimental findings provide support for prior reports on the benefits of yogic breathing and mindful Zen meditation for pain and depressed affect. However, chronic pain patients may require more guidance to obtain therapeutic benefit from reduced breathing rates.     

Physiotherapy for patients with chronic pain: An operant-behavioural approach

The aim of this study was to demonstrate a physiotherapy application of operant-behavioural theoretical principles for patients with chronic pain. The goals of treatment from this theoretical orientation were to decrease pain behaviours and suffering and to improve function. The treatment programme incorporated members from a number of disciplines, including physicians, physiotherapists and psychologists, over the course of 3 weeks. Four female patients with intractable, heterogeneous chronic pain complaints comprised the sample. Each subject was studied in a single-case format, using a multiple-baseline design. Standardised measures of function, exercise tolerance and pain were collected the first, second and third week of treatment for each subject. The data were analysed graphically. Clinically significant reductions in degree of suffering were noted for three subjects; pain intensity either increased or remained constant for all subjects. There were improvements in several of the function and exercise tolerance measures for three subjects between the first and third week measurements. The results of these case studies demonstrate the potential and efficacy of applying operant-behavioural principles to physiotherapy for reduction of suffering and improvement in physical functioning.     

Mechanical and heat hyperalgesia highly predict clinical pain intensity in patients with chronic musculoskeletal pain syndromes

Multiple abnormalities in pain processing have been reported in patients with chronic musculoskeletal pain syndromes. These changes include mechanical and thermal hyperalgesia, decreased thresholds to mechanical and thermal stimuli (allodynia), and central sensitization, all of which are fundamental to the generation of clinical pain. Therefore, we hypothesized that quantitative sensory tests may provide useful predictors of clinical pain intensity of such patients. Our previous studies of fibromyalgia (FM) patients have shown statistically significant correlations of quantitative sensory test results with clinical pain intensity, including mechanical spatial summation, number of pain areas, wind-up, and wind-up aftersensations. Although these tests predicted up to 59% of the variance in FM clinical pain intensity, their expense and technical complexities limited widespread use in clinical practice and trials. Thus, we developed practical tests of primary (mechanical) and secondary (heat) hyperalgesia that also strongly predict clinical pain intensity in patients with chronic musculoskeletal pain disorders. Thirty-six individuals with FM, 24 with local musculoskeletal pain, and 23 normal controls underwent testing of mechanical and heat hyperalgesia at the shoulders and hands. All subjects rated experimental pains using an electronic visual analog scale. Using either heat or pressure pain ratings as well as tender point counts and negative affect as predictors, up to 49.4% of the patients' variance of clinical pain intensity could be estimated. Results of this study emphasize the important contributions of peripheral and central factors to both local and widespread chronic pain. Overall, measures of mechanical and heat hyperalgesia in combination with tender point and negative affect provided powerful predictors of clinical pain intensity in chronic musculoskeletal pain patients that can be readily used in clinical practice and trials. PERSPECTIVE: Simple tests of mechanical and heat hyperalgesia can predict large proportions of the variance in clinical pain intensity of chronic musculoskeletal pain patients and thus are feasible to be included in clinical practice and clinical trials.     

The natural course of chronic benign pain in childhood and adolescence: a two-year population-based follow-up study

STUDY OBJECTIVE: To assess the course of chronic benign pain in childhood and adolescence longitudinally.Setting. Cohort of children with chronic pain recruited from the open population. PATIENTS: A cohort of 987 children and adolescents aged 0-18 years with chronic pain (continuous or recurrent pain>3 months), who were identified in a previous population-based prevalence study, were approached for a two-year follow-up study. Subjects were asked to keep a 3-week diary on their pain and to fill out questionnaires about background factors, pain and pain-related consequences. This assessment was repeated annually for two years. RESULTS: At baseline, 254 subjects reported chronic benign pain; of these, 124 (48%) and 77 (30%) subjects still experienced chronic benign pain at one-year and two-year follow-up, respectively. Except for the estimated pain intensity, which decreased marginally, pain remained stable over the follow-up period. Minor changes occurred in the consequences of pain; the main changes were a decrease of the impact of pain on the child's behavior, social functioning and use of health care. Subjects with persistent pain (9.4%) differed from those with non-persistent pain in frequency, history and location of the pain, emotional problems and their mother's health. CONCLUSIONS: Chronic benign pain in childhood and adolescence is common, and seems to persist in a considerable proportion (30-45%), although pain generally does not deteriorate over time.     

A randomized, placebo-controlled trial of bupropion sustained release in chronic low back pain.

Clinical trials of the efficacy of antidepressant drugs in patients with chronic low back pain have had mixed results, possibly because of the different mechanisms of action of the drugs that have been studied. Because bupropion has a mechanism of action that differs from other antidepressants and has shown efficacy in neuropathic pain, a randomized, placebo-controlled, 2-period crossover trial was conducted to evaluate its efficacy in subjects with chronic low back pain. The primary efficacy variable was mean daily diary pain intensity ratings, and secondary pain intensity and relief outcomes included weekly pain intensity ratings, the McGill Pain Questionnaire (MPQ) Present Pain Intensity scale, pain relief ratings, and satisfaction with pain relief ratings. Adverse events were also assessed throughout the trial. Analyses were performed of an intention-to-treat sample of 44 patients, only 3 of whom met criteria for neuropathic low back pain. Daily and weekly pain intensity ratings, the MPQ Present Pain Intensity scale, and pain relief ratings were not significantly different following treatment with bupropion sustained release (SR) vs. placebo. These results suggest that bupropion SR was not significantly better than placebo in the treatment of patients with non-neuropathic chronic low back pain. PERSPECTIVE: Antidepressant medications that have both noradrenergic and serotonergic effects appear to have greater efficacy in patients with chronic low back pain than those with only serotonergic activity. We studied bupropion because it inhibits the reuptake of both norepinephrine and dopamine, but found no evidence of efficacy in patients with non-neuropathic chronic low back pain.     

The relationship between activity and chronic back pain

Thirty chronic back pain patients participated in a study of the relationship between activity level and pain intensity. Activity is presumed to cause increases in pain. If this is true, then chronic sufferers should regulate their activities so that when they have pain, they should avoid participating in activities. This assumption was examined by comparing pain intensity with several measures of activity. The activity measures ranged from global reports to observed behaviour. The results showed that patients do report a connection between activity and pain on a global interview question, and patients with much pain tend to make lower ratings of ability to participate in daily activities. However, no significant correlation was found between pain intensity and actual activity levels as measured by self-monitoring or observed behaviour in a test situation. These findings provide little support for the idea that activity level is directly related to chronic pain intensity and they underscore the importance of comprehensive behavioural assessment.     

Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain

The objectives of the study were (1) to carry out a systematic review to assess the analgesic efficacy and the adverse effects of acupuncture compared with placebo for back and neck pain and (2) to develop a new tool, the Oxford Pain Validity Scale (OPVS), to measure validity of findings from randomized controlled trials (RCTs), and to enable ranking of trial findings according to validity within qualitative reviews. Published RCTs (of acupuncture at both traditional and non-traditional points) were identified from systematic searching of bibliographic databases (e.g. MEDLINE) and reference lists of retrieved reports. Pain outcome data were extracted with preference given to standardized outcomes such as pain intensity. Information on adverse effects was also extracted. All included trials were scored using a five-item 0-16 point validity scale (OPVS). The individual RCTs were ranked according to their OPVS score to enable more weight to be placed on the trials of greater validity when drawing an overall conclusion about the efficacy of acupuncture for relieving neck and back pain. Statistical analyses were carried out on the OPVS scores to assess the relationship between trial finding (positive or negative) and validity. Thirteen RCTs met the inclusion criteria. Five trials concluded that acupuncture was effective, and eight concluded that it was not effective for relieving back or neck pain. There was no obvious difference between the findings of trials using traditional and non-traditional points. Using the new OPVS scale, the validity scores of the included trials ranged from 4 to 14. There was no significant relationship between OPVS score and trial finding (positive versus negative). Authors' conclusions did not always agree with their data. We drew our own conclusions (positive/negative) based on the data presented in the reports. Re-analysis using our conclusions showed a significant relationship between OPVS score and trial finding, with higher validity scores associated with negative findings. OPVS is a useful tool for assessing the validity of trials in qualitative reviews. With acupuncture for chronic back and neck pain, we found that the most valid trials tended to be negative. There is no convincing evidence for the analgesic efficacy of acupuncture for back or neck pain.     

A psychophysiological causal model of pain report validity.

The validity of the pain report is vitally important but difficult to assess because pain is a personal experience. Human laboratory research affords an opportunity to investigate validity because one can measure the consistency and sensitivity of pain ratings produced in response to known stimuli. This article presents 2 levels of evidence characterizing the validity of the pain report measure. The within-subject agreement of pain report with known stimulus variation quantifies the criterion validity, or accuracy, of the measure. Causal modeling defines a second, between-subject, level of construct validity by suggesting a psychophysiological mechanism determining the observed individual variation in accuracy. We analyzed pain rating data obtained in a laboratory study where 100 subjects (56 men and 44 women) experienced varied levels of painful fingertip electrical stimulation, delivered in random order across 144 trials. Unknown to the subjects, there were only 3 stimulus intensities. Accuracy, defined operationally as the proportion of variance in pain report explained by stimulus level, ranged from 0.07 to 0.91 with a median of 0.64. Hypothesized determinants of accuracy comprised current intensity, event-related late near field evoked potentials, skin conductance response, heart rate, and pupil diameter change. We limited the evoked potential measures to the amplitude of the negative peak at 150 msec (N150amp) and combined the latter 3 measures to form a single index of overall sympathetic nervous system arousal (Arousal). Although men chose higher stimulus levels for the experiment and had higher Arousal than did women, their mean pain reports and their Accuracy did not differ from those of female subjects. We constructed a sequence of path analysis models designed to clarify the causal contributions of current intensity, N150amp, and Arousal, and to determine whether these relationships differ in men and women. The final model revealed a direct causal chain. Stimulus current determined the amplitude of N150amp (possibly an indicator of attention). N150amp in turn determined Arousal, and Arousal emerged as the sole determinant of the Accuracy of the pain report. In addition, this latter effect differed across the sexes. Men who experienced higher levels of Arousal gave more accurate pain reports than those who had lower levels, but women who had higher levels of Arousal gave less accurate pain reports than those with lower levels. Thus construct validation emerged, not from direct stimulus-response correlation, but from the elucidation of a causal chain that related stimulus to response.     

Biofeedback of somatosensory event-related potentials: can individual pain sensations be modified by biofeedback-induced self-control of event-related potentials?

This study investigates the effects of biofeedback based upon event-related brain potentials evoked by nociceptive electrical stimuli. In a visual and monetary feedback paradigm, 10 subjects received positive feedback within one training session when systematically showing two different behavior patterns: one pattern correlated with a decrease (down-training) and one with an increase (up-training) of the peak-to-peak size of the N150-P260 complex, respectively. Training conditions were changed randomly from trial to trial over 300 trials. All subjects achieved control on both behavior patterns resulting in a simultaneous modification of the size of this complex according to the training conditions. Furthermore, the individual pain report measured with a visual analogue scale was altered in accordance with the biofeedback-induced behavioral modifications. A decrease in subjective pain report was achieved after down-training while an increase was observed after the up-training.     

Expressive dimensions of pain catastrophizing: An observational study in adolescents with chronic pain

Investigated was the relationship between pain catastrophizing and pain intensity in adolescents suffering from chronic pain (n = 38) and the extent to which they expressed communicative pain and pain-related protective behaviours. Adolescents were observed on video performing a 2-Min Walk Test (2MWT). Behaviours were coded on videotape. The adolescents’ verbalizations about the 2MWT were also rated by their parents. Analyses revealed that higher levels of catastrophic thinking about pain were associated with higher levels of facial pain expressions and verbalizations about their pain experience, beyond the effects of age, gender, pain duration and pain intensity. Pain-related protective behaviours did not vary with the adolescents’ level of pain catastrophizing, but varied with pain intensity. The findings corroborate the functional distinctiveness of different types of pain behaviours. The results are discussed in terms of the processes linking (1) catastrophizing to communicative pain behaviours and (2) pain to pain-related protective behaviours.     

Effect of Iyengar yoga therapy for chronic low back pain

Low back pain is a significant public health problem and one of the most commonly reported reasons for the use of Complementary Alternative Medicine. A randomized control trial was conducted in subjects with non-specific chronic low back pain comparing Iyengar yoga therapy to an educational control group. Both programs were 16 weeks long. Subjects were primarily self-referred and screened by primary care physicians for study of inclusion/exclusion criteria. The primary outcome for the study was functional disability. Secondary outcomes including present pain intensity, pain medication usage, pain-related attitudes and behaviors, and spinal range of motion were measured before and after the interventions. Subjects had low back pain for 11.2+/-1.54 years and 48% used pain medication. Overall, subjects presented with less pain and lower functional disability than subjects in other published intervention studies for chronic low back pain. Of the 60 subjects enrolled, 42 (70%) completed the study. Multivariate analyses of outcomes in the categories of medical, functional, psychological and behavioral factors indicated that significant differences between groups existed in functional and medical outcomes but not for the psychological or behavioral outcomes. Univariate analyses of medical and functional outcomes revealed significant reductions in pain intensity (64%), functional disability (77%) and pain medication usage (88%) in the yoga group at the post and 3-month follow-up assessments. These preliminary data indicate that the majority of self-referred persons with mild chronic low back pain will comply to and report improvement on medical and functional pain-related outcomes from Iyengar yoga therapy.     

Investigation of central pain processing in shoulder pain: converging results from 2 musculoskeletal pain models

Recent reports suggest deficits in conditioned pain modulation (CPM) and enhanced suprathreshold heat pain response (SHPR) potentially play a role in the development of chronic pain. The purpose of this study was to investigate whether central pain processing was altered in 2 musculoskeletal shoulder pain models. The goals of this study were to determine whether central pain processing: 1) differs between healthy subjects and patients with clinical shoulder pain; 2) changes with induction of exercise-induced muscle pain; and 3) changes 3 months after shoulder surgery. Fifty-eight patients with clinical shoulder pain and 56 age- and sex-matched healthy subjects were included in these analyses. The healthy cohort was examined before inducing EIMP, and 48 and 96 hours later. The clinical cohort was examined before shoulder surgery and 3 months later. CPM did not differ between the cohorts, however; SHPR was elevated for patients with shoulder pain compared to healthy controls. Induction of acute shoulder pain with EIMP resulted in increased shoulder pain intensity but did not change CPM or SHPR. Three months following shoulder surgery, clinical pain intensity decreased but CPM was unchanged from preoperative assessment. In contrast, SHPR was decreased and showed values comparable with healthy controls at 3 months. Therefore, the present study suggests that: 1) clinical shoulder pain is associated with measurable changes in central pain processing; 2) exercise-induced shoulder pain did not affect measures of central pain processing; and 3) elevated SHPR was normalized with shoulder surgery. Collectively our findings support neuroplastic changes in pain modulation were associated with decreases in clinical pain intensity only, and could be detected more readily with thermal stimuli. PERSPECTIVE: Longitudinal studies involving quantitative sensory testing are rare. In exploring 2 musculoskeletal shoulder pain models (exercise-induced muscle pain and surgical pain), conditioned pain modulation was unchanged from pre- to post-assessment in both models. Suprathreshold heat pain response decreased after shoulder surgery and was comparable to healthy controls, suggesting this measure may be sensitive to decreases in clinical pain intensity.     

A comparison of models describing reports of disability associated with chronic pain.

We examined pain-related disability from two perspectives. A disability model, suggesting that disability is a direct consequence of pain, is compared with a symptom perception model emphasizing individual differences in perception and report of physical symptoms. Disability estimates (reported activity interference and employment status) were obtained from a sample of 179 patients with chronic pain. Using multiple regression analyses, we showed that distress, symptom reporting, and pain intensity accounted for comparable levels of variance in reports of activity interference. When we controlled for distress, the frequency of reporting physical symptoms made the largest contribution to prediction of this kind of disability (14%). Neither symptom report or pain intensity was useful in predicting the more objective disability criterion of employment status. Results were interpreted as probable evidence against a disability model of pain-related disability and suggest the relative importance of individual cognitive differences in symptom responsivity.     

Comparative reliability and validity of chronic pain intensity measures.

Reliable and valid measures of pain are essential for conducting research on chronic pain. The purpose of this longitudinal study was to compare the reliability and validity of several measures of pain intensity. One hundred twenty-three patients with chronic pain were administered telephone interview versions of 0-10 scales of current, worst, least and average pain, immediately prior to beginning a multidisciplinary treatment program. The measures were administered again to these subjects 2 weeks (n=108), 1 month (n=106) and 2 months (n=105) after the end of treatment. The validity (defined as ability to detect changes in pain intensity over the course of treatment up to the 2-month follow-up assessment) and reliability (defined as stability over time in the 2 months after treatment) of these four measures and of composite combinations of these measures were examined. Contrary to prediction, the composite measures did not show a statistically significant superiority to the individual ratings in terms of their ability to detect change in pain intensity from pre-treatment to various points after treatment. The composite scores did, however, show greater stability than did the individual ratings after treatment. The practical conclusions of this study are; (1), individual 0-10 pain intensity ratings have sufficient psychometric strengths to be used in chronic pain research, especially research that involves group comparison designs with relatively large sample sizes, but, (2), composites of 0-10 ratings may be more useful when maximal reliability is necessary, (e.g. in studies with relatively small sample sizes, or in clinical settings where monitoring of changes in pain intensity in individuals is needed).     

Chronic postsurgical pain after nitrous oxide anesthesia

Nitrous oxide is an antagonist at the N-methyl-d-aspartate receptor and may prevent the development of chronic postsurgical pain. We conducted a follow-up study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA) trial patients to evaluate the preventive analgesic efficacy of nitrous oxide after major surgery. The ENIGMA trial was a randomized controlled trial of nitrous oxide-based or nitrous oxide-free general anesthesia in patients presenting for noncardiac surgery lasting more than 2 hours.Using a structured telephone interview, we contacted all ENIGMA trial patients recruited in Hong Kong (n = 640). We recorded the severity of postsurgical pain of at least 3 months’ duration that was not due to disease recurrence or a pre-existing pain syndrome, using the modified Brief Pain Inventory. The impact of postsurgical pain on quality of life was also measured. Pain intensity, opioid and other analgesic requirements during the first week of surgery, were retrieved from the trial case report form and medical records. A total of 46 (10.9%) patients reported pain that persisted from the index surgery, and 39 (9.2%) patients had severe pain. In addition, patients with chronic pain rated poorly in all attributes of the quality-of-life measures compared with those who were pain free. In a multivariate analysis, nitrous oxide decreased the risk of chronic postsurgical pain. In addition, severe pain in the first postoperative week, wound complication, and abdominal incision increased the risk of chronic pain. In conclusion, chronic postsurgical pain was common after major surgery in the ENIGMA trial. Intraoperative nitrous oxide administration was associated with a reduced risk of chronic postsurgical pain.