HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Diagnosing and managing prescription opioid use disorder in patients prescribed opioids for chronic pain in Australian general practice settings: a qualitative study using the theory of Planned Behaviour.

BACKGROUND: Chronic pain is a debilitating and common health issue. General Practitioners (GPs) often prescribe opioids to treat chronic pain, despite limited evidence of benefit and increasing evidence of harms, including prescription Opioid Use Disorder (pOUD). Australian GPs are worried about the harms of long-term opioids, but few are involved in the treatment of pOUD. There is little research on GPs' experiences diagnosing and managing pOUD in their chronic pain patients. METHODS: This qualitative research used semi-structured interviews and a case study to investigate GPs' experiences through the lens of the Theory of Planned Behaviour (TPB). TPB describes three factors, an individual's perceived beliefs/attitudes, perceived social norms and perceived behavioural controls. Participants were interviewed via an online video conferencing platform. Interviews were transcribed verbatim and thematically analysed. RESULTS: Twenty-four GPs took part. Participants were aware of the complex presentations for chronic pain patients and concerned about long-term opioid use. Their approach was holistic, but they had limited understanding of pOUD diagnosis and suggested that pOUD had only one treatment: Opioid Agonist Treatment (OAT). Participants felt uncomfortable prescribing opioids and were fearful of difficult, conflictual conversations with patients about the possibility of pOUD. This led to avoidance and negative attitudes towards diagnosing pOUD. There were few positive social norms, few colleagues diagnosed or managed pOUD. Participants reported that their colleagues only offered positive support as this would allow them to avoid managing pOUD themselves, while patients and other staff were often unsupportive. Negative behavioural controls were common with low levels of knowledge, skill, professional supports, inadequate time and remuneration described by many participants. They felt OAT was not core general practice and required specialist management. This dichotomous approach was reflected in their views that the health system only supported treatment for chronic pain or pOUD, not both conditions. CONCLUSIONS: Negative beliefs, negative social norms and negative behavioural controls decreased individual behavioural intention for this group of GPs. Diagnosing and managing pOUD in chronic pain patients prescribed opioids was perceived as difficult and unsupported. Interventions to change behaviour must address negative perceptions in order to lead to more positive intentions to engage in the management of pOUD.

Measurement properties of the Regular Physical Exercise Adherence Scale (REPEAS) in individuals with chronic pain.

OBJECTIVE: To examine the measurement properties of the Regular Physical Exercise Adherence Scale (REPEAS) in Brazilians with chronic pain. METHODS: Cross-sectional and longitudinal design (washout period for reliability). The study was conducted in two Brazilian states, Maranhão and São Paulo, and included Brazilian adults, irregular exercisers, former exercisers or non-exercise practitioners, aged 18 to 59 years and with chronic pain. The instruments used in this study were: the REPEAS, the Numerical Pain Rating Scale (NPRS), the Baecke Habitual Physical Activity Questionnaire (BHPAQ), the Pain Self-Efficacy Questionnaire (PSEQ), and the Roland-Morris Disability Questionnaire for general pain (RMDQ-g). The evaluation focused on structural validity, construct validity, reliability (with standard error of measurement and minimum detectable change), internal consistency, and floor and ceiling effects. RESULTS: The two-dimensional structure was tested through confirmatory factor analysis, which resulted in adequate fit indeces: chi-square values/degrees of freedom = 1.541, Tucker-Lewis Index = 0.966, comparative fit index = 0.974, root mean square error of approximation = 0.074, and standardized root mean square residual = 0.068. Additionally, satisfactory factor loadings (> 0.40) were obtained. Test-retest reliability and internal consistency were adequate for the environmental factors domain (intraclass correlation coefficient [ICC] = 0.79, Cronbach's alpha = 0.88) and the personal factors domain (ICC = 0.97, Cronbach's alpha = 0.93). In hypothesis testing for construct validity, we observed a significant correlation with magnitude below 0.30 of the environmental factors domain of the REPEAS with RMDQ-g, PSEQ and sport domain of the BHPAQ. For the personal factors domain, we observed a significant correlation with a magnitude of 0.30 to 0.50 with RMDQ-g, PSEQ, and sport domain of the BHPAQ, and below 0.30 with leisure domain of the BHPAQ. No floor or ceiling effects were found for the REPEAS domains. CONCLUSION: The REPEAS is a valid instrument with a two-dimensional internal structure consisting of 12 items. It has a reliable construct and is suitable for use in the clinical and epidemiological context for adults with chronic pain in Brazil.

A model linking emotional dysregulation in neurodivergent people to the proprioceptive impact of joint hypermobility.

Emotional feelings are putatively ascribed to central representation of bodily states in the context of expectation and uncertainty in both internal state and external world. Neurodivergent people are more likely to experience co-occurring mental health challenges, although mechanistic insights underpinning this association are scarce. We therefore undertook a study to test whether imprecise processing of proprioceptive error signals may underlie the connection between neurodivergence and emotional dysregulation. In a cohort of people with complex chronic conditions, including chronic pain/fatigue, and complex trauma, and in a comparison group, we assessed presence of neurodivergence, variant connective tissue manifested through joint hypermobility, and emotional dysregulation. We present a data-informed conceptual model showing that variant connective tissue determines whether proprioceptive surprise is linked with emotional dysregulation in neurodivergent individuals. We suggest that future research in this area may have important clinical implications for the interaction of mental and physical wellbeing in neurodivergent people. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Brief behavioral intervention for chronic pain in integrated primary care: What are we waiting for?

Despite high rates of pain-related concerns among primary care patients and associated increases in health care costs (Gore et al., 2012; Mills et al., 2016), psychological or behavioral treatments that are well suited for use in integrated primary care (IPC) settings remain sparsely implemented. Psychological treatment for chronic pain has been recommended for many years (Darnall, 2021; Institute of Medicine (US) Committee on Advancing Pain Research, Care and Education, 2011; Kligler et al., 2018), and the emphasis on the application of nonpharmacological treatment has intensified following concerns about opioid safety. There is abundant empirical support for the use of psychological treatment for chronic pain, such as cognitive behavioral therapy (CBT) in specialty settings (Williams et al., 2021). The evidence to support the use of "brief treatments" in IPC is in a comparatively early stage. The limited state of the research might suggest that brief behavioral intervention for chronic pain is years away from being ready for translation to everyday clinical practice. But why wait? We therefore conducted a focused narrative review of peer-reviewed research on brief psychotherapy for chronic pain in adults that could be feasibly employed in IPC settings through more widely adopted models, such as primary care behavioral health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding public perceptions and discussions on diseases involving chronic pain through social media: cross-sectional infodemiology study.

BACKGROUND: Chronic pain is a highly prevalent medical condition that negatively impacts quality of life and is associated with considerable functional disability. Certain diseases, such as fibromyalgia, headache, paraplegia, neuropathy, and multiple sclerosis, manifest with chronic pain. OBJECTIVE: The aim of this study is to examine the number and type of tweets (original or retweet) related to chronic pain, as well as to analyze the emotions and compare the societal impact of the diseases under study. METHODS: We investigated tweets posted between January 1, 2018, and December 31, 2022, by Twitter users in English and Spanish, as well as the generated retweets. Additionally, emotions were extracted from these tweets and their diffusion was analyzed. Furthermore, the topics most frequently discussed by users were collected. RESULTS: A total of 72,874 tweets were analyzed, including 44,467 in English and 28,407 in Spanish. Paraplegia represented 23.3% with 16,461 of the classified tweets, followed by headache and fibromyalgia with 15,337 (21.7%) and 15,179 (21.5%) tweets, respectively. Multiple sclerosis generated 14,781 tweets (21%), and the fewest tweets were related to neuropathy with 8,830 tweets (12.5%). The results showed that the primary emotions extracted were "fear" and "sadness." Additionally, the reach and impact of these tweets were investigated through the generated retweets, with those related to headaches showing the highest interest and interaction among users. CONCLUSION: Our results underscore the potential of leveraging social media for a better understanding of patients suffering from chronic pain and its impact on society. Among the most frequently encountered topics are those related to treatment, symptoms, or causes of the disease. Therefore, it is relevant to inform the patient to prevent misconceptions regarding their illness.

On Natality: Beginning to Be Limited.

Through the personal reflection on chronic pain, the author engages the question of how clinicians and their patients manage various forms of loss within the clinical encounter. The notion of developmental grief is introduced as a stepping-stone from phallicism to genitality, whereby the capacity to grieve and thus tolerate limitedness enables growth. Hannah Arendt's concept of natality is offered as a hopeful corrective to the resistance to accepting limitations.

The Chronic Wound-Related Pain Model: Holistic Assessment and Person-Centered Treatment.

Chronic wound-related pain is a complex biopsychosocial experience that is experienced spontaneously at rest and exacerbated during activities. Tissue debridement, trauma at dressing change, increased bioburden or infection, exposure of periwound skin to moisture, and related treatment can modulate chronic wound-related pain. Clinicians should consider multimodal and multidisciplinary management approach that take into account the biology, emotions, cognitive thinking, social environment, and other personal determinants of pain. Unresolved pain can have a significant impact on wound healing, patients' adherence to treatment, and individual's quality of life.

Beyond pain: the influence of psychological factors on functional status in fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is characterised by chronic widespread pain, often associated with fatigue, sleep disturbance, cognitive and mood impairment. Pain is a complex and multidimensional experience that significantly impacts personal, social, and professional functioning. Psychological factors related to chronic pain include catastrophising and self-efficacy in managing the painful condition. Therefore, this study explores the influence of chronic pain and related psychological factors on functional outcomes in FM patients. METHODS: In this study, 91 Italian patients with FM were assessed using an online questionnaire. The questionnaire included instruments to assess pain, such as the Numerical Rating Scale (NRS) and the Brief Pain Inventory (BPI), psychological characteristics, such as the Pain Self-Efficacy Questionnaire (PSEQ) and the Pain Catastrophizing Scale (PCS), and health-related quality of life with the 12-item Short Form Survey (SF-12). Multiple regression models were run, using the Interference subscale of the BPI and the physical and mental components of the SF-12 as outcomes, and the NRS, PCS and PSEQ scales as predictors. RESULTS: Our analysis revealed that in our model, both PCS and PSEQ were significant predictors of BPI-Interference (PCS: ß=0.29; p=0.001; PSEQ: ß=-0.36; p<0.001); NRS and PSEQ significantly predicted SF-12-Physical score (NRS: ß=-0.32; p=<0.001; PSEQ: ß=.50; p<0.001); PCS was found to be the only significant predictor of SF-12-Mental scores (ß=-0.53; p<0.001). CONCLUSIONS: Our results suggested that psychological variables such as catastrophic thinking and self-efficacy play a significant role in determining daily functioning and physical and mental health status in FM patients, showing greater influence than pain intensity.

Systematic review and narrative synthesis of the experiences of individuals with chronic pain participating in digital pain management interventions.

BACKGROUND: The use of digital pain management interventions has grown since the Covid 19 pandemic. The aim of this study was to systematically review and synthesise evidence from qualitative studies regarding the experiences of individuals with chronic pain participating in digital pain management interventions in primary care and community settings. METHODS: Fourteen databases were searched, as well as citation tracking and hand-searching reference lists of included articles. The latest search was completed by 07/07/2023. Qualitative studies of patient and carer perspectives of digital pain management interventions for adults aged 18 and over with non-malignant chronic pain were included. All studies were appraised for quality using the Critical Appraisal Skills Programme Qualitative Checklist. A narrative synthesis approach was used to synthesise the findings. Normalisation Process Theory was used to understand how individuals with chronic pain make sense of digital pain management interventions and incorporate knowledge, skills and strategies learnt into their day-to-day lives. RESULTS: Eleven studies, encompassing both digital applications for use on smartphones/ mobile devices and user-directed online modular programmes, were included in the synthesis. Three main themes and related subthemes were identified from the included studies: 1) Making sense of the digital intervention (Subthemes: Tailoring to user's needs; Human contact and support; Accessibility of the digital intervention; Personal and environmental factors affecting engagement with digital interventions); 2) Initiating and Maintaining Behaviour Change (Subthemes: Planning activity; Being active); and 3) Personal Growth (Subthemes: Gaining understanding and skills; Gaining and acting on feedback; Negotiating a new relationship with pain). CONCLUSION: Recommendations. The key recommendations from our findings are that digital pain management interventions should provide: Specific and tailored information for individual participants.Focus on changing attitudes and behaviours and reframing perceptions of pain.Structured goal setting with prompts to review goals.Potential healthcare professional support alongside the digital intervention.Limitations of the review. To reduce bias, it would have been preferable for more than one author to independently fully analyse each paper and to identify themes and sub-themes. Instead, the identified themes and sub-themes were discussed with two other authors in the team (ES, LW) to reach a consensus view on final themes and sub-themes. One author (JS) received a Research Internship and Research Initiation Award funded by NIHR Applied Research Collaboration (ARC) Wessex (https://www.arc-wx.nihr.ac.uk/) and NHS England (https://www.england.nhs.uk/). The protocol for this review was registered with the National Institute of Health Research (NIHR) PROSPERO international database for registering systematic reviews (PROSPERO Registration Number CRD42021257768).

"What helps your back pain?" A qualitative analysis of pain management strategies in opioid-treated adults with chronic low back pain.

OBJECTIVE: The purpose of this qualitative analysis was to better understand what pain management strategies adults with opioid-treated chronic low back pain (CLBP) found most helpful. DESIGN: A subgroup of participants from a larger randomized control trial of two psychological interventions were asked: "What helps your back pain?" at baseline and 12 months (exit) in brief, video-recorded interviews. Videos were analyzed using qualitative thematic content analysis utilizing Transana™. SETTING: Participants were recruited from the community and outpatient clinics in three United States sites. PARTICIPANTS: Seventy-nine adults with long-term (≥3 months) opioid-treated (≥15 mg/day morphine equivalent) CLBP. MAIN OUTCOME MEASURE(S): Participants' baseline and exit qualitative responses to the question "What helps your back pain?" RESULTS: At baseline, participants identified medication (n = 63), body position (n = 59), thermal application (n = 50), physical activity (n = 49), and stretching (n = 24) as the CLBP management strategies they found helpful. At exit, the reports of medication (n = 55), physical activity (n = 41), and stretching (n = 21) were often considered helpful for CLBP and remained relatively stable, while position (n = 36) and thermal application (n = 35) strategies were mentioned less frequently and psychological strategies (n = 29) were mentioned more frequently (up from n = 5) compared to baseline. CONCLUSIONS: Over time, the reports of medication and active pain management strategies, eg, physical activity, remained stable, while the reports of some passive pain management strategies, eg, position and thermal, declined over time. Increased use of psychological strategies implies that study interventions were incorporated as useful pain self-management strategies.

Substance P's Impact on Chronic Pain and Psychiatric Conditions-A Narrative Review.

Substance P (SP) plays a crucial role in pain modulation, with significant implications for major depressive disorder (MDD), anxiety disorders, and post-traumatic stress disorder (PTSD). Elevated SP levels are linked to heightened pain sensitivity and various psychiatric conditions, spurring interest in potential therapeutic interventions. In chronic pain, commonly associated with MDD and anxiety disorders, SP emerges as a key mediator in pain and emotional regulation. This review examines SP's impact on pain perception and its contributions to MDD, anxiety disorders, and PTSD. The association of SP with increased pain sensitivity and chronic pain conditions underscores its importance in pain modulation. Additionally, SP influences the pathophysiology of MDD, anxiety disorders, and PTSD, highlighting its potential as a therapeutic target. Understanding SP's diverse effects provides valuable insights into the mechanisms underlying these psychiatric disorders and their treatment. Further research is essential to explore SP modulation in psychiatric disorders and develop more effective treatment strategies.

Measuring Pain-related Behavioral Inhibition and Behavioral Activation System Responses: Further Validity Evidence for the Pain Responses Scale.

OBJECTIVES: The Pain Responses Scale and its Short Form (PRS-SF) were recently developed to assess the affective, behavioral, and cognitive responses to pain based on the behavioral inhibition system (BIS) and behavioral activation system (BAS) model of chronic pain. The purpose of this study was to provide additional tests of the psychometric properties of the PRS-SF in a new sample of individuals with chronic pain. METHODS: A sample of Spanish adults (N = 190) with chronic non-cancer pain completed a translated version of the PRS-SF and a battery of questionnaires measuring validity criteria hypothesized the be associated with BIS and BAS activation, including measures of sensitivity to punishment, sensitivity to reward, pain intensity, pain interference, catastrophizing, and pain acceptance. RESULTS: Confirmatory factor analysis supported a 4-factor structure for the PRS-SF assessing despondent, escape, approach, and relaxation responses (S-B χ 2 [5] = 1.49, Comparative Fit Index = 0.99, Non-Normed Fit Index = 0.99, root-mean-square error of approximation = 0.051, Akaike Information Criterion = 4113.66), with marginal internal consistency for 1 scale (relaxation) and adequate to good internal consistency for the others. The pattern of associations found between the PRS-SF Scale scores and the validity criterion supports the validity of the instrument. CONCLUSION: The results provide additional support for the validity of the 4 PRS-SF Scale scores, and the reliability of 3 of the scales. If these findings are replicated in future research, investigators may wish to administer more items from the original Relaxation Scale when assessing this domain to ensure adequate reliability for this scale. The other items from the PRS-SF assessing despondent, escape, and approach responses appear to provide at least adequate reliability. When used in this way, the PRS-SF may be used to measure BIS and BAS responses to pain to: (1) provide further tests of the BIS-BAS model of chronic pain and/or (2) understand the potential mediating effects of BIS and BAS responses on the effects of psychological pain treatments to help determine which specific responses are most responsible for the benefits of treatment, and, therefore, which responses should be specifically targeted to enhance treatment response.

Chronic pain in children and young people with cerebral palsy: a narrative review of challenges, advances, and future directions.

BACKGROUND: Cerebral palsy (CP), the most common physical disability of childhood, is often accompanied by a range of comorbidities including pain. Pain is highly prevalent in children and young people with CP, yet has been poorly understood, inaccurately assessed, and inadequately managed in this vulnerable population. This narrative review presents recent research advances for understanding and managing pain in children and young people with CP, focusing on chronic pain, and highlights future research directions. MAIN BODY: Pain prevalence rates in CP vary due to different methodologies of studies. Recent systematic reviews report up to 85% of children experience pain; higher in older children, females, and those with dyskinesia and greater motor impairment. Research examining the lived experience perspectives of children and their families demonstrate that even those with mild motor impairments have pain, children want to self-report pain where possible to feel heard and believed, and management approaches should be individualized. Notably, many children with cognitive and communication impairments can self-report their pain if adjustments are provided and they are given a chance. Past inadequacies of pain assessment in CP relate to a focus on pain intensity and frequency with little focus on pain interference and coping, a lack of tools appropriate for the CP population, and an assumption that many children with cognitive and/or communication limitations are unable to self-report. Recent systematic reviews have identified the most reliable and valid assessment tools for assessing chronic pain. Many were not developed for people with CP and, in their current form, are not appropriate for the spectrum of physical, communication, and cognitive limitations seen. Recently, consensus and co-design in partnership with people with lived experience and clinicians have identified tools appropriate for use in CP considering the biopsychosocial framework. Modifications to tools are underway to ensure feasibility and applicability for the spectrum of abilities seen. CONCLUSION: Recent research advances have improved our understanding of the prevalence, characteristics and lived experience of chronic pain, and refined assessment methods in children and young people with CP. However, the very limited evidence for effective and novel management of chronic pain in this population is where research should now focus.

Conceptualisations of pain amongst resettled Nepali-speaking Bhutanese adults in rural and regional Australia.

INTRODUCTION: Nepali-speaking Bhutanese refugees have been subject to one of the largest resettlement programs in the world and experience higher rates of chronic pain when compared to the general population. The purpose of this study was to explore qualitative conceptualisations of chronic pain among a group of Nepali-speaking Bhutanese adults with a refugee background who relocated to rural and regional Australia. METHODS: Participants included 22 individuals (females n=15) with chronic pain, who took part in structured qualitative focus groups exploring their experiences of chronic pain. Data were analysed using thematic analysis and five main themes were developed. RESULTS: The themes were: (1) pain is persistent and creates suffering, (2) pain is subjective and poorly understood, (3) pain is a biomedical problem that needs to be solved, (4) pain is complex and more than a biomedical problem, and (5) coping with pain is multi-faceted.Some participants viewed pain through a predominantly biomedical lens, and some recognised social and psychological factors as contributors to pain. Overwhelmingly, the participants believed pain is complex and multifaceted, requiring active and passive strategies for management, some of which are culturally informed. CONCLUSION: The experiences of resettled Nepali-speaking Bhutanese refugees living with pain are important to elucidate to improve healthcare inequalities among this marginalised group. This research will inform future assessment guidelines and treatment programs for Nepali-speaking Bhutanese adults living with chronic pain.

Comparative analysis of centrally mediated and inflammatory pain experiences amongst patients diagnosed with rheumatoid arthritis: A multimethods study.

BACKGROUND: The identification of pain originating from distinct biological processes may lead to individualised pain treatment. In this study, we aimed to explore the pain experiences of patients with rheumatoid arthritis (RA), differentiating between those predominantly exhibiting features of peripheral inflammatory versus centrally mediated pain. METHODS: Through a multimethods approach we (i) quantitatively analysed the differences in pain descriptors between patients diagnosed with RA experiencing peripheral inflammatory and centrally mediated pain, utilising the Short Form-McGill Pain Questionnaire which includes the pain visual analogue scale (VAS) and (ii) qualitatively explored their subjective pain experiences grounded in the biopsychosocial model, commonly applied in chronic pain. RESULTS: Participants with centrally mediated pain reported higher pain scores on the VAS, used a wider range of pain descriptors, and a higher proportion selected each descriptor compared to those with inflammatory pain (p < .001). The qualitative analysis revealed the centrally mediated pain group's experiences were overwhelming and relentless, struggling to precisely articulate the nature of their pain. In contrast, individuals with inflammatory pain expressed their pain in more tangible terms and shared their adaptive and coping strategies. Importantly, both groups revealed the substantial psychological, functional and social impacts of their pain, highlighting the often 'invisible' and misunderstood nature of their symptoms. CONCLUSION: This study has gained a deeper insight into the pain experiences of patients living with RA, particularly in differentiating between centrally mediated and inflammatory types of pain, potentially facilitating a more individualised approach to pain treatment. PATIENT CONTRIBUTION: Patients actively participated in the study conception and design. This engagement includes collaboration with key stakeholders, such as members of the National Rheumatoid Arthritis Society and Patient Research Partners (PRPs), who provided continuous feedback and guidance throughout the research process. Specifically, the qualitative element was coproduced with two PRPs, who were involved in co-leading the focus groups and data analysis.