Human Studies

Acupuncture is one of the therapeutic resources used for the management of chronic pain. Variability in outcome measurements in randomized clinical trials of non-oncologic chronic pain (RCT-NOCP) generates inconsistencies in determining effects of treatments. The objective of this survey was to assess the adherence to the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in the measurement of RCT-NOCP of acupuncture. This methodological research made a systematic search for eligible studies from different sources of information. Eligible studies included those with number of patients ≥100, who randomized and allocated patients with chronic non-oncologic pain to be treated with acupuncture or with "sham" acupuncture, or non-acupuncture. This research included the recommendations for IMMPACT in the measurement of RCT-NOCP: presence of outcomes pain, physical function, emotional state and improvement perception of patient, the source of the outcome information pain and the tools used to measure such domains. From a total of 1,386 studies, 24 were included in this survey. Eleven studies presented low risk of bias. Pain outcome was measured in 23 studies, physical function in 22 studies, emotional state in 14 studies and improvement perception of patient in one study. As for the pain outcome, the patient was the information source in 50% of the studies. The measurement tools recommended for IMMPACT were included in eight studies (35%) that evaluated pain, one study that evaluated the emotional state (7%), and one study that evaluated the improvement perception and satisfaction of patient. It was observed that studies which did not adhere to the recommendations had more favorable results for acupuncture in the outcome pain. This study concludes that randomized clinical trials that used acupuncture to manage chronic pain failed to adhere to IMMPACT recommendations. Clinical societies and IMMPACT do not share the same recommendations. This fact reflects in the diversity of outcomes and instruments adopted in the studies, making it difficult to compare the results.

Visceroception is a complex phenomenon comprising the sensation, interpretation, and integration of sensations along the gut-brain axis, including pain or defecatory urgency. Stress is considered a crucial risk factor for the development and maintenance of disorders of gut-brain signaling, which are characterized by altered visceroception. Although the broad role of stress and stress mediators in disturbed visceroception is widely acknowledged, the putative contribution of chronic stress to variations in normal visceroception remains incompletely understood. We aimed to elucidate the role of chronic stress in shaping different facets of visceroception. From a well-characterized, large sample of healthy men and women (N = 180, 50% female), volunteers presenting with low (n = 57) and elevated (n = 61) perceived chronic stress were identified based on the validated Trier Inventory for Chronic Stress (TICS). Visceral sensitivity together with perceived and recalled intensity and defecatory urgency induced by repeated rectal distensions was experimentally assessed, and compared between low and elevated stress groups. Subgroups were compared regarding state anxiety and salivary cortisol concentrations across experimental phases and with respect to psychological measures. Finally, in the full sample and in chronic stress subgroups, a recall bias in terms of a discrepancy between the perception of experimentally-induced symptoms and their recall was tested. Participants with elevated chronic stress presented with increased state anxiety and higher cortisol concentrations throughout the experimental phases compared to the group with low chronic stress. Group differences in visceral sensitivity were not evident. The elevated stress group perceived significantly higher urgency during the stimulation phase, and recalled substantially higher feelings of urgency induced by rectal distensions, while perceived and recalled intensity were comparable between groups. Volunteers with elevated stress exhibited a recall bias in terms of a higher recall relative to mean perception of urgency, whereas no such bias was observed for the intensity of experimental visceral stimulation. Our findings in healthy men and women provide first evidence that the troublesome symptom of urgency might be particularly modifiable by chronic stress and support the relevance of memory biases in visceroception. These results may help to disentangle the impact of chronic stress on altered visceroception in disturbances of gut-brain communication.

Successfully predicting the susceptibility of individuals to placebo analgesics will aid in developing more effective pain medication and therapies, as well as aiding potential future clinical use of placebos. In pursuit of this goal, we analyzed healthy and chronic pain patients' patterns of responsiveness during conditioning rounds and their links to conditioned placebo analgesia and the mediating effect of expectation on those responses. We recruited 579 participants (380 healthy, 199 with temporomandibular disorder [TMD]) to participate in a laboratory placebo experiment. Individual pain sensitivity dictated the temperatures used for high- and low-pain stimuli, paired with red or green screens, respectively, and participants were told there would be an analgesic intervention paired with the green screens. Over two conditioning sessions and one testing session, participants rated the painfulness of each stimulus on a visual analogue scale from 0 to 100. During the testing phase, the same temperature was used for both red and green screens to assess responses to the placebo effect, which was defined as the difference between the average of the high-pain-cue stimuli and low-pain-cue stimuli. Delta scores, defined as each low-pain rating subtracted from its corresponding high-pain rating, served as a means of modeling patterns of conditioning strength and placebo responsiveness. Latent class analysis (LCA) was then conducted to classify the participants based on the trajectories of the delta values during the conditioning rounds. Classes characterized by persistently greater or increasing delta scores during conditioning displayed greater placebo analgesia during testing than those with persistently lower or decreasing delta scores. Furthermore, the identified groups' expectation of pain relief acted as a mediator for individual placebo analgesic effects. This study is the first to use LCA to discern the relationship between patterns of learning and the resultant placebo analgesia in chronic pain patients. In clinical settings, this knowledge can be used to enhance clinical pain outcomes, as chronic pain patients with greater prior experiences of pain reduction may benefit more from placebo analgesia.

Fatigue is commonly reported by people with chronic pain. The purpose of the current study was to examine Acceptance and Commitment Therapy (ACT), based on the Psychological Flexibility (PF) model, for fatigue in chronic pain. This study included 354 adults attending an interdisciplinary ACT-oriented treatment for chronic pain. T-tests and analyses of clinically meaningful change were used to investigate participant improvements in fatigue interference after the treatment. Pearson's correlations and hierarchical regressions were conducted to investigate associations between improvement in fatigue interference and improvements in PF processes. Finally, mixed effects models were used to explore associations between baseline fatigue interference and changes in treatment outcome measures. Participants improved in fatigue interference (d=.37), pain, some PF processes, and daily functioning (d=.18-1.08). 39.7% of participants demonstrated clinically meaningfully improvements in fatigue interference. Changes in fatigue interference was associated with changes in pain, PF processes and daily functioning, |r|= .20-.46. Change in fatigue interference was associated with change in pain acceptance independent of change in pain, β=-.36, p<.001. However, baseline fatigue interference did not predict any treatment outcome. Overall, people with fatigue appeared to benefit from the ACT-oriented interdisciplinary treatment for chronic pain, and relatively higher levels of fatigue did not appear to impede this benefit. ACT-based treatments may benefit people with chronic pain and fatigue. Future studies including experimental designs, and studies investigating other PF processes, are needed to better understand the utility of ACT for co-morbid fatigue and pain.