Neuromuscular electrical stimulation to combat cognitive aging in people with spinal cord injury: protocol for a single case experimental design study.

INTRODUCTION: Individuals with spinal cord injury (SCI) can experience accelerated cognitive aging. Myokines (factors released from muscle cells during contractions), such as brain-derived neurotrophic factor (BDNF), are thought to have beneficial effects on cognition. Neuromuscular electrical stimulation (NMES) was shown to elicit a large release of myokines. However, the effects of NMES on cognitive function have not been studied. OBJECTIVE: To present the study protocol for a clinical trial evaluating the effects of NMES aimed at improving cognition and BDNF. METHODS: A replicated randomized three-phases single-case experimental design (SCED) with sequential multiple baseline time series and a single-armed prospective trial will be conducted with 15 adults with chronic SCI (> 12 months after injury) above L1 neurological level undergoing 30-min quadriceps NMES, 3 days per week for 12 weeks. MAIN STUDY ENDPOINTS: Primary endpoint is cognitive performance (assessed by a smartphone test) conducted three times per week during the baseline phase with random duration of 3 to 8 weeks, the intervention phase of 12 weeks, and the follow-up phase of 3 weeks after a no measurement rest period of 12 weeks. Secondary endpoints are changes in BDNF levels and cognitive performance measured before the baseline period, before and after intervention and after a 12 weeks follow-up. CONCLUSION: This will be the first study investigating the effects of 12 weeks NMES on both cognition and BDNF levels in individuals with SCI. The SCED results provide information on individual treatment effect courses which may direct future research. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05822297, 12/01/2023).

Pavlovian-to-instrumental transfer in individuals with chronic pain.

Avoidance of pain has been argued to be key factor leading pain events to chronic disability. In this respect, research has focused on investigating the working mechanisms of avoidance's acquisition. Avoidance of painful stimuli has been traditionally studied using a combination of Pavlovian and Instrumental procedures. However, such approach seems to go against real-life scenarios where avoidance is commonly acquired more readily. Using a novel pain avoidance paradigm, we tested whether pain avoidance can be installed in absence of associations between a cue and pain omission, and whether such avoidance differs between pain patients and healthy controls. Participants first learned to avoid painful stimuli by pressing a grip bar. Then, they passively encountered pairings of one geometrical shape with pain and of another geometrical shape without pain. Lastly, participants encountered the geometrical shapes while being able to use the grip bar. Results showed that participants pressed the bar more vigorously when encountering the previously pain-related shape compared to the pain-unrelated shape. This effect did not seem to differ between pain patients and healthy control. Our study could inspire a new way in measuring avoidance in pain, possibly paving the way to better understanding how avoidance is installed in chronic pain.

The Activity Management Inventory for Pain (AMI-P): Initial Development and Validation of a Questionnaire Based on Operant Learning and Energy Conservation Models of Activity Management.

OBJECTIVES: Activity management is an important treatment component in chronic pain programs. However, there are shortcomings in measures of this construct, leading to inconsistencies in research findings. Here, we describe the development of the Activity Management Inventory for Pain (AMI-P). MATERIALS AND METHODS: The AMI-P was developed by a group of international researchers with extensive expertise in both chronic pain and activity management. The initial evaluation of the AMI-P items included 2 studies that were both conducted in Canadian tertiary pain care centers. RESULTS: The resulting 20-item measure has 3 behavior scales (Rest, Alternating Activity, and Planned Activity), and 4 goal scales (Feel Less Pain, Get More Done, Complete the Task, and Save Energy). The behavior scales evidenced marginal to good internal consistency and test-retest reliability, and a moderate positive association with an existing pacing measure. The Rest and Alternating Activity scales were associated with greater pain interference, the Alternating Activity and Planned Activity scales were associated with less satisfaction with social roles, and the Planned Activity scale was associated with fewer depressive symptoms. The Alternating Activity scale increased significantly from pretreatment to posttreatment. All goal scales were positively associated with all behavior scales. The Feel Less Pain goal scale was positively associated with measures of avoidance and pain interference, while the Get More Done goal scale was negatively associated with measures of depressive symptoms and overdoing. DISCUSSION: The findings support the reliability and validity of the AMI-P scales, while also highlighting the complexity and multidimensional aspects of activity management.

Reconceptualizing sensitization in pain: back to basics.

Fillingim RB. Redefining sensitization could be a sensitive issue. PAIN Rep 2024;9:e1126.

A randomized controlled trial of graded exposure treatment (GET living) for adolescents with chronic pain.

ABSTRACT: Graded exposure treatment (GET) is a theory-driven pain treatment that aims to improve functioning by exposing patients to activities previously feared and avoided. Combining key elements of GET with acceptance-based exposure, GET Living (GL) was developed for adolescents with chronic pain (GL). Based on robust treatment effects observed in our single-case experimental design pilot trial of GL (NCT01974791), we conducted a 2-arm randomized clinical trial comparing GL with multidisciplinary pain management (MPM) comprised of cognitive behavioral therapy and physical therapy for pain management (NCT03699007). A cohort of 68 youth with chronic musculoskeletal pain (M age 14.2 years; 81% female) were randomized to GL or MPM. Owing to COVID-19 restrictions, 54% of participants received zoom video delivered care. Assessments were collected at baseline, discharge, as well as at 3-month and 6-month follow-up. Primary outcomes were self-reported pain-related fear and avoidance. Secondary outcomes were child functional disability and parent protective responses to child pain. As hypothesized, GL improved in primary and secondary outcomes at 3-month follow-up. Contrary to our superiority hypothesis, there was no significant difference between GL and MPM. Patients reported both GL and MPM (in person and video) as credible and were highly satisfied with the treatment experience. Next steps will involve examining the single-case experimental design data embedded in this trial to facilitate an understanding of individual differences in treatment responses (eg, when effects occurred, what processes changed during treatment within the treatment arm). The current findings support GET Living and MPM for youth with chronic pain.

Reliability and Validity of the Avoidance of Daily Activities Photo Scale for Patients With Shoulder Pain (ADAP Shoulder Scale).

OBJECTIVE: The Avoidance of Daily Activities Photo Scale for Patients With Shoulder Pain (ADAP Shoulder Scale) was developed to assess pain-related avoidance behavior during daily activities in people with shoulder pain. However, its measurement properties must be verified according to international guidelines. As such, this study investigated the following 4 measurement properties of the ADAP Shoulder Scale: reliability, measurement errors, convergent validity, and floor and ceiling effects. METHODS: The sample comprised 100 individuals with chronic shoulder pain (43 men and 57 women; mean duration of symptoms of 29.7 [SD = 89.0] months; mean age of 44.9 [SD = 15.9] years). The mean test-retest reliability range was 5 days via the intraclass correlation coefficient (ICC). Measurement errors included the standard error of measurement and the minimal detectable change. Convergent validity was analyzed by applying the Pearson correlation with the Tampa Scale for Kinesiophobia, Pain Catastrophizing Scale, and Shoulder Pain and Disability Index. RESULTS: The ADAP Shoulder Scale showed excellent test-retest reliability, both in all domains and in the total score [ICC(2,1) = 0.94; 95% CI = 0.92-0.96]. The standard errors of measurement for the free-movement, high-effort, and self-care domains were 8.1%, 6.0%, and 7.6%, respectively. The minimal detectable change for the total score of the ADAP Shoulder Scale was 16.0%. The total score of the ADAP Shoulder Scale was low to moderately correlated with the total scores of the Tampa Scale for Kinesiophobia (r = 0.52), Pain Catastrophizing Scale (r = 0.30), and Shoulder Pain and Disability Index (r = 0.72). No floor or ceiling effects were detected in the total score. CONCLUSION: The ADAP Shoulder Scale is a reliable, valid instrument for assessing avoidance behavior in adults who have chronic shoulder pain and are not athletes. IMPACT: This study provides evidence that the ADAP Shoulder Scale is appropriate for clinical and practical use in people with chronic shoulder pain.

In search of conditioned pain: an experimental analysis.

ABSTRACT: There is an ongoing debate about whether pain can be classically conditioned, but surprisingly, evidence is scarce. Here, we report 3 experiments investigating this idea. In a virtual reality task, healthy participants were approached and touched near or on their hand with a coloured pen (blue or yellow). During acquisition, participants learned that one of the colours of the pen (CS+) was predictive of a painful electrocutaneous stimulus (ECS) whereas the other coloured pen (CS-) was not. During the test phase, more frequent reports of experiencing an US when none was delivered ("false alarm") for the CS+ vs CS- qualified as evidence of conditioned pain. Notable differences between experiments were that the US was delivered when the pen touched a spot between the thumb and index finger (experiment 1; n = 23), when it virtually touched the hand (experiment 2; n = 28) and when participants were informed that the pen caused pain rather than simply predicting something (experiment 3; n = 21). The conditioning procedure proved successful in all 3 experiments: Self-reported fear, attention, pain, fear, and US expectancy were higher ( P < 0.0005) for the CS+ than the CS-. There was no evidence for conditioned pain in experiment 1, but there was some evidence in experiments 2 and 3. Our findings indicate that conditioned pain may exist, albeit most likely in rare cases or under specific situations. More research is needed to understand the specific conditions under which conditioned pain exists and the underlying processes (eg, response bias).

Experimental Pain Picture System (EPPS): Development and Validation.

Pain-related pictures are useful for studying how individuals respond to pain-related stimulation. Such pictures can occasionally be found in databases for affective pictures. However, a validated database specifically for pain-related pictures is not available yet. In 2 experiments (N = 185 and 103, respectively), we developed and validated the Experimental Pain Pictures System (EPPS). In both experiments, negative valence, arousal, and painfulness ratings were compared between neutral-, sad-, and pain-related pictures. The pain-related pictures represented both deep and superficial somatic pain. Across the 2 experiments, pain-related pictures were judged as more negative, arousing, and painful than neutral pictures and more painful than sad pictures. The final EPPS contains 50 pictures of different painful events considered moderately to highly painful by participants. The EPPS is a valuable tool for studying pain-related responses, as it gives researchers a choice among many validated pictures depicting different types of pain, increasing the comparability between studies. PERSPECTIVE: This article presents the validation of the experimental pain pictures system, which consists of a set of pain-related pictures. The experimental pain pictures system is composed of pictures depicting different types of pain. Participants rated all the pictures as being negative, arousing, and painful.

The effect of high versus low cognitive load on the development of nociceptive hypersensitivity: The roles of sympathetic arousal, sex and pain-related fear.

BACKGROUND: According to limited-capacity theories of attention, less attentional resources remain available when engaging in a high- versus a low-demanding cognitive task. This may reduce the perceived intensity and the evoked cortical responses of concomitant nociceptive stimuli. Whether and how the competition for limited attentional resources between a cognitive task and pain impacts the development of long-lasting hypersensitivity is unclear. METHODS: Eighty-four healthy participants were randomized into a low or high cognitive load group. Low-frequency electrical stimulation (LFS) of the skin was used to induce secondary hypersensitivity. We hypothesized that performing the high-load task during LFS would reduce the development of hypersensitivity. We examined whether painfulness, nonpain-related sympathetic arousal, or sex related to hypersensitivity, by assessing intensity and unpleasantness of mechanical pinprick stimulation. During task execution, we recorded steady-state evoked potentials evoked by LFS and skin conductance level for sympathetic arousal. Afterwards, participants reported task difficulty and LFS-related fear. For the primary outcomes, we used mixed analysis of variances. RESULTS: The results confirmed the difference in cognitive load. Although LFS successfully induced hypersensitivity, the high-load task did not reduce its development. Next, the steady-state evoked potentials did not differ between groups. Hypersensitivity correlated positively with pain-related fear and negatively with skin conductance level before LFS, despite the lack of group differences in skin conductance level. We did not find any sex differences in hypersensitivity. CONCLUSIONS: These results do not confirm that high cognitive load or sex modulate hypersensitivity, but show associations with pain-related fear and non-pain-related sympathetic arousal. SIGNIFICANCE: Previous research has mainly focused on cognitive load effects on the perception of acute painful stimuli. Yet this study extends our understanding by investigating cognitive load effects on the development of long-lasting secondary hypersensitivity, a common aspect in numerous persistent pain conditions. As cognitive tasks are presented during a painful procedure inducing secondary hypersensitivity, we test the long-lasting effects of cognitive load. Additionally, we used psychophysiological measurements to explored potential underlying mechanisms involving limited attentional resources and sympathetic arousal.

Better Together. Group versus individual Cognitive-Behavioral Therapy for tinnitus: A Multiple-Baseline Single-Case Experimental Design.

OBJECTIVES: Chronic tinnitus is effectively treated through cognitive-behavioral therapy (CBT). Both group and individual CBT for tinnitus are effective, but no study has directly compared the two. The current study explores group versus individual CBT for tinnitus. DESIGN: A multiple-baseline single-case experimental design was employed to observe changes within/between individual and group treatments. Six participants started a 10-week CBT protocol and were equally divided into individual or group treatment. Participants were exchanged between treatments at random time points. Diary data included 14 variables on tinnitus experience (e.g. annoyance and distraction) and wellbeing (e.g. happiness and stress). Five male participants (59- to 67-year-old) completed treatment. RESULTS: Randomization tests comparing means between individual and group treatments did not reveal significant differences. Analysis of data overlap and trend (Tau-U) revealed minor significant improvements for seven variables (50%) in group treatment as compared to individual treatment. Diminished happiness and activity levels were observed in participants who went from group to individual treatment. CONCLUSIONS: Low effect sizes and homogeneity of sample restrict the generalizability of data. Group CBT indicated potential benefits when compared to individual CBT. Social learning may be an underlying process in group delivery boosting tinnitus recovery. Findings are limited to male patients with chronic disabling tinnitus.

Fear influences phantom sound percepts in an anechoic room.

Aims and hypotheses: In an environment of absolute silence, researchers have found many of their participants to perceive phantom sounds (tinnitus). With this between-subject experiment, we aimed to elaborate on these research findings, and specifically investigated whether-in line with the fear-avoidance model of tinnitus perception and reactivity-fear or level of perceived threat influences the incidence and perceptual qualities of phantom sound percepts in an anechoic room. We investigated the potential role of individual differences in anxiety, negative affect, noise sensitivity and subclinical hearing loss. We hypothesized that participants who experience a higher level of threat would direct their attention more to the auditory system, leading to the perception of tinnitus-like sounds, which would otherwise be subaudible, and that under conditions of increased threat, narrowing of attention would lead to perceptual distortions. Methods: In total, N = 78 normal-hearing volunteers participated in this study. In general, the study sample consisted of young, mostly female, university students. Their hearing was evaluated using gold-standard pure tone audiometry and a speech-in-noise self-test (Digit Triplet Test), which is a sensitive screening test to identify subclinical hearing loss. Prior to a four-minute stay in an anechoic room, we randomized participants block design-wise in a threat (N = 37) and no-threat condition (N = 41). Participants in the threat condition were deceived about their hearing and were led to believe that staying in the room would potentially harm their hearing temporarily. Participants were asked whether they perceived sounds during their stay in the room and rated the perceptual qualities of sound percepts (loudness and unpleasantness). They were also asked to fill-out standardized questionnaires measuring anxiety (State-Trait Anxiety Inventory), affect (Positive and Negative Affect Schedule) and noise sensitivity (Weinstein Noise Sensitivity Scale). The internal consistency of the questionnaires used was verified in our study sample and ranged between α = 0.61 and α = 0.90. Results: In line with incidence rates reported in the literature, 74% of our participants reported having heard tinnitus-like sounds in the anechoic room. Speech-in-noise identification ability was comparable for both groups of participants. The experimental manipulation of threat was proven to be effective, as indicated by significantly higher scores on a Threat Manipulation Checklist among participants in the threat condition as compared to those in the no-threat condition (p < 0.01). Nevertheless, participants in the threat condition were as likely to report tinnitus percepts as participants in the no-threat condition (p = 1), and tinnitus percepts were not rated as being louder (p = 0.76) or more unpleasant (p = 0.64) as a function of level of threat. For participants who did experience tinnitus percepts, a higher level of threat was associated with a higher degree of experienced unpleasantness (p < 0.01). These associations were absent in those who did not experience tinnitus. Higher negative affect was only slightly associated with higher ratings of tinnitus unpleasantness (p < 0.01). Conclusion: Whereas our threat manipulation was successful in elevating the level of fear, it did not contribute to a higher percentage of participants perceiving tinnitus-like sounds in the threat condition. However, higher levels of perceived threat were related to a higher degree of perceived tinnitus unpleasantness. The findings of our study are drawn from a rather homogenous participant pool in terms of age, gender, and educational background, challenging conclusions that are applicable for the general population. Participants generally obtained normophoric scores on independent variables of interest: they were low anxious, low noise-sensitive, and there was little evidence for the presence of subclinical hearing loss. Possibly, there was insufficient variation in scores to find effects.

The role of intolerance of uncertainty when solving the exploration-exploitation dilemma.

When making behavioral decisions, individuals need to balance between exploiting known options or exploring new ones. How individuals solve this exploration-exploitation dilemma (EED) is a key research question across psychology, leading to attempting to disentangle the cognitive mechanisms behind it. A potential predictive factor of performance in an EED is intolerance of uncertainty (IU), an individual difference factor referring to the extent to which uncertain situations are reported to be aversive. Here, we present the results of a series of exploratory analyses in which we tested the relationship between IU and performance in an EED task. For this, we compiled data from 3 experiments, in which participants received the opportunity to exploit different movements in order to avoid a painful stimulus and approach rewards. For decomposing performance in this task, we used different computational models previously employed in studies on the EED. Then, the parameters of the winning model were correlated with the scores of participants in the IU scale. Correlational and cluster analyses, within both frequentists and Bayesian frameworks, did not provide strong evidence for a relation between EED and IU, apart from the decay rate and the subscale "tendency to become paralyzed in the face of uncertainty". Given the theoretical relation between EED and IU, we propose research with different experimental paradigms.

Review article: exclude or expose? The paradox of conceptually opposite treatments for irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut-brain interaction (DGBI) maintained by interacting biological, psychological, and social processes. Interestingly, there are two contrasting yet evidence-based treatment approaches for reducing IBS symptoms: exclusion diets such as those low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) and exposure-based cognitive-behavioural therapy (CBT). Exclusion diets recommend patients avoid foods thought to be symptom-inducing, whereas exposure-based CBT encourages patients to expose themselves to foods. AIMS: To address the paradox of conceptually opposite exclusion diets and exposure-based CBT for IBS. METHODS: In this conceptual review, we describe the rationale, practical implementation, evidence base and strengths and weaknesses of each treatment. We conducted up-to-date literature search concerning the low FODMAP diet and CBT, and performed a secondary analysis of a previously conducted trial to illustrate a key point in our review. RESULTS: The low FODMAP diet has demonstrated efficacy, but problems with adherence, nutritional compromise, and heightened gastrointestinal-specific anxiety raise caution. Exposure-based CBT has demonstrated efficacy with substantial evidence for gastrointestinal-specific anxiety as a key mechanism of action. Mediation analysis also showed that increased FODMAP intake mediated decreased symptom severity in exposure-based CBT. However, there is minimal evidence supporting which treatment "works best for whom" and how these approaches could be best integrated. CONCLUSIONS: Even though exclusion diets and exposure-based CBT are conceptually opposite, they each have proven efficacy. Clinicians should familiarise themselves with both treatments. Further research is needed on predictors, mechanisms and moderators of treatment outcomes.

Error Processing and Pain: A New Perspective.

Errors put organisms in danger. Upon error commission, error processing allows for the updating of behavior that proved ineffective in light of the current context and goals, and for the activation of behavioral defensive systems. Pain, on the other hand, signals actual or potential danger to one's physical integrity and, likewise, motivates protective behavior. These parallels suggest the existence of cross-links between pain and error processing but so far their relationship remains elusive. In this review, we tie together findings from the field of pain research with those from electroencephalography studies on error processing [specifically the Error Related Negativity (ERN) and Positivity (Pe)]. More precisely, we discuss 3 plausible associations: Firstly, pain may enhance error processing as it increases error salience. Secondly, persons fearful of pain may be particularly vigilant towards painful errors and thus show a stronger neural response to them. Thirdly, the ERN as a component of the neural response to error commission is considered an endophenotype of threat sensitivity. As high sensitivity to pain threats is known to incite avoidance behavior, this raises the intriguing possibility that neural signatures of error processing predict pain-related protective behaviors, such as avoidance. We propose an integration of these findings into a common framework to inspire future research. PERSPECTIVE: Inspired by research in anxiety disorders, we discuss the potential bi-directional relationships between error processing and pain, and identify future directions to examine the neural and psychological processes involved in acute and chronic pain and respective avoidance behavior.