How Should the Use of Opioids Be Regulated to Motivate Better Clinical Practice?

This article describes historical and political reasons for-and devastating consequences of-US opioid prescribing policy since the 1990s, which has restricted opioid prescribing for pain less than for treating opioid use disorder (OUD) treatment. This article considers merits and drawbacks of a new diagnostic category and proposes a regulatory and clinical framework for prescribing long-term opioid therapy for pain and for prescribing opioids to treat OUD.

How Should Risks and Benefits of Short-Acting Opioids Be Evaluated in the Care of Inpatients With OUD?

Severe opioid withdrawal, risk of patient-initiated discharge, and some inpatients' use of unregulated substances prompt clinical and ethical questions considered in this commentary on a case. Short-acting opioids can be used to manage inpatients' pain and opioid use disorder (OUD) withdrawal symptoms. Including evidence-based interventions-such as naloxone kits, substance use equipment, and supervised consumption-in some inpatients' care plans may make those patients safer and reduce their risk of death. These and other strategies align with clinicians' ethical duties to minimize harms and maximize benefits for inpatients with OUD.

Exploring the effect of wound related pain on psychological stress, inflammatory response, and wound healing.

AIMS AND OBJECTIVES: The relationship between pain and poor healing is intricate, potentially mediated by psychological stress and aberrations in inflammatory response. The purpose of this study was to examine the biopsychosocial model of pain by assessing the relationships between pain, stress, inflammation and healing in people with chronic wounds. DESIGN: This was a 4-week prospective observational study to explore the relationship of pain, stress, inflammation and wound healing in a convenience sample of patients with chronic wounds in a chronic care hospital in Canada. METHODS: Only subjects over 18 with chronic wounds were recruited into the study. Chronic wounds were defined by the duration of wounds for more than 4 weeks of various aetiologies including wounds caused by pressure injuries, venous disease, arterial insufficiency, surgery or trauma and diabetic neuropathy. Participants were evaluated for pain by responding to the Brief Pain Inventory-Short Form, the McGill Pain Questionnaire-Short Form and the Leeds Assessment of Neuropathic Symptoms and Signs scale. Stress was measured by the Perceived Stress Scale (PSS). All wounds were assessed with the Pressure Ulcer Scale for Healing tool. The levels of matrix metalloproteinases were analysis by obtaining wound fluid from all participants. RESULTS: A total of 32 individuals with chronic wounds participated in the study. Correlation analysis indicated pain severity was positively and significantly related to pain interference, McGill Pain Questionnaire scores, neuropathic pain and matrix metalloproteinase levels. Logistic regression was used to determine the predictors for high or low perceived stress. The only significant variable that contributed to the stress levels was BPI-I. Results suggested that participants who experienced higher levels of pain interference also had an increased odds to report high level of stress by 1.6 times controlling for all other factor in the model. CONCLUSION: Pain is a complex biopsychosocial phenomenon affecting quality of life in people with chronic wounds. Results of this study identified a significant relationship between pain, stress and wound healing.

Disordered but effective: short linear motifs as gene therapy targets for hyperexcitability disorders.

Multiple approaches have targeted voltage-gated sodium (Nav) channels for analgesia. In this issue of the JCI, Shin et al. identified a peptide aptamer, NaViPA1, carrying a short polybasic motif flanked by serine residues in a structurally disordered region of loop 1 in tetrodotoxin-sensitive (TTX-S) but not tetrodotoxin-resistant (TTX-R) channels. NaViPA1h inhibited TTX-S NaV channels and attenuated excitability of sensory neurons. Delivery of NaViPA1 in vivo via adeno-associated virions restricted its expression to peripheral sensory neurons and induced analgesia in rats. Targeting of short linear motifs in this manner may provide a gene therapy modality, with minimal side effects due to its peripherally-restricted biodistribution, which opens up a therapeutic strategy for hyperexcitability disorders, including pain.

Psychosocial Characteristics by Pain Presence and Limitations Among Older Adults.

PURPOSE: To compare psychosocial outcomes of older adults according to pain experience. METHOD: Using cross-sectional 2021 data from the National Health and Aging Trends Study, we examined psychosocial characteristics in older adults (N = 3,376) divided into three groups: no pain, pain without activity limitations, and activity-limiting pain. RESULTS: In multiple regression models, older adults with activity-limiting pain compared to those without pain had significantly higher depression, anxiety, and fear of falling, as well as reduced positive affect, self-realization, self-efficacy, resilience, and social participation. Older adults with non-activity-limiting pain had significantly higher social participation than those without pain, but no differences in self-realization, self-efficacy, or resilience. CONCLUSION: Pain is strongly associated with all psychosocial outcomes, especially in older adults with activity-limiting pain. Future research should examine the impact of self-realization, self-efficacy, resilience, and social participation on activity limitations. [Journal of Gerontological Nursing, 50(7), 27-34.].

Real-time and video-recorded pain assessment in beef cattle: clinical application and reliability in young, adult bulls undergoing surgical castration.

Bovine pain assessment relies on validated behavioral scales related to normal and pain-related behaviors. This study investigated the reliability and applicability of real-time and video-recorded pain assessment, and their agreement, in young, adult bulls undergoing surgical castration. Ten Nelore and nine Angus bulls underwent general anesthesia and surgical castration. Three-minute real-time observations and simultaneous videos were recorded at - 48 h (M0), before sedation, under fasting (M1), after surgery, 3 h after sternal recumbency (M2), after rescue analgesia (M3) and at 24 h (M4). Animals received morphine (after M2), dipyrone (after M3), and flunixin meglumine after surgical castration (M4). Two trained evaluators assessed real-time (n = 95) and video-recorded time-points (n = 95) using the Unesp-Botucatu Cattle Pain Scale (UCAPS). Both assessment methods inferred 'very good' reliability (≥ 0.81) with minimal bias, however, video-recorded assessment (4.33 ± 2.84) demonstrated slightly higher scores compared to real-time (3.08 ± 2.84). The results from this study suggest that UCAPS can be used in real-time or video-recorded to assess pain and guide analgesic therapy in cattle.

Associations between adverse childhood experiences and pain in middle-aged and older adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Effects of different exercise types and cycles on pain and quality of life in breast cancer patients: A systematic review and network meta-analysis.

PURPOSE: To determine the effect of different combinations of different exercise modalities with different training cycles on the improvement of quality of life and pain symptoms in breast cancer patients. METHODS: The databases PubMed, Web of Science, Embase, and Scopus were searched through a computer network with a search deadline of 23 August 2023. Two researchers independently screened the literature, extracted data and performed methodological quality assessment of the included literature, and then performed the corresponding statistical analyses and graphing using stata17.0. RESULTS: Thirty-six randomized control trial (RCT) studies involving 3003 participants and seven exercise modalities were included. Most of the exercise modalities improved patients' quality of life compared to usual care, with long-term aerobic combined with resistance exercise [SMD = 0.83,95% CI = 0.34,1.33,p = 0.001] and YOGA [SMD = 0.61,95% CI = 0.06,1.16,p = 0.029] treatments having a significant effect. For pain and fatigue-related outcome indicators, the treatment effect was not significant for all exercise modalities included in the analysis compared to the control group, but tended to be beneficial for patients. CONCLUSION: Long-term aerobic combined with resistance exercise was the most effective in improving quality of life and fatigue status in breast cancer patients, and aerobic exercise was more effective in improving pain symptoms in breast cancer patients.

Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

BACKGROUND: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. METHODS: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. RESULTS: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. CONCLUSIONS: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Psychopathy, pain, and pain empathy: A psychophysiological study.

The present study examined whether people higher in psychopathy experienced less self-reported and psychophysiological nociceptive pressure than people lower in psychopathy. We also examined whether psychopathy affects empathy for others' pain via self-reported and psychophysiological measures. Three hundred and sixty-nine students (18-78 years; M = 26, SD = 9.34) were screened for psychopathic traits using the Youth Psychopathy Inventory (YPI). Stratified sampling was used to recruit 49 adults residing in the highest (n = 23) and lowest (n = 26) 20% of the psychopathy spectrum. Using skin conductance response (SCR) and self-report responses, participants responded to individually adjusted intensities of pneumatic pressure and others' pain images and completed self-reported psychopathy and empathy measures (Triarchic Psychopathy Measure, TriPm; Interpersonal Reactivity Index, IRI). People higher in psychopathy self-reported feeling less nociceptive pressure compared to people lower in psychopathy, yet we did not find any differences in SCR to nociceptive pressure. However, when viewing other people in pain, the high psychopathy group displayed lower SCR and lower self-reported empathy compared to those lower in psychopathy. Our results suggest psychopathic traits relate to problems empathising with others' pain, as well as the perception of nociceptive pressure. We also show support for the theory of dual harm which has been receiving increasing attention. Consequently, psychopathy interventions should focus both on recognising and empathising with the pain of others.

Empathy incites a stable prosocial decision bias.

Empathy toward suffering individuals serves as potent driver for prosocial behavior. However, it remains unclear whether prosociality induced by empathy for another person's pain persists once that person's suffering diminishes. To test this, participants underwent functional magnetic resonance imaging while performing a binary social decision task that involved allocation of points to themselves and another person. In block one, participants completed the task after witnessing frequent painful stimulation of the other person, and in block two, after observing low frequency of painful stimulation. Drift-diffusion modeling revealed an increased initial bias toward making prosocial decisions in the first block compared with baseline that persisted in the second block. These results were replicated in an independent behavioral study. An additional control study showed that this effect may be specific to empathy as stability was not evident when prosocial decisions were driven by a social norm such as reciprocity. Increased neural activation in dorsomedial prefrontal cortex was linked to empathic concern after witnessing frequent pain and to a general prosocial decision bias after witnessing rare pain. Altogether, our findings show that empathy for pain elicits a stable inclination toward making prosocial decisions even as their suffering diminishes.

Technology-Based Music Interventions to Reduce Anxiety and Pain Among Patients Undergoing Surgery or Procedures: Systematic Review of the Literature.

BACKGROUND: Hospitalized patients undergoing surgery or procedures may experience negative symptoms. Music is a nonpharmacological complementary approach and is used as an intervention to reduce anxiety, stress, and pain in these patients. Recently, music has been used conveniently in clinical situations with technology devices, and the mode of providing music is an important factor in technology-based music interventions. However, many reviews have focused only on the effectiveness of music interventions. OBJECTIVE: We aimed to review randomized controlled trials (RCTs) of technology-based music interventions for reducing anxiety and pain among patients undergoing surgery or procedures. We examined the clinical situation, devices used, delivery methods, and effectiveness of technology-based music interventions in primary articles. METHODS: The search was performed in the following 5 electronic databases: PubMed, MEDLINE (OvidSP), CINAHL complete, PSYCINFO, and Embase. This systematic review focused on technology-based music interventions. The following articles were included: (1) RCTs, (2) studies using interactive technology (eg, smartphones, mHealth, tablets, applications, and virtual reality), (3) empirical studies reporting pain and anxiety outcomes, and (4) English articles published from 2018 to 2023 (as of January 18, 2023). The risk of bias was assessed using the Cochrane Risk of Bias tool version 2. RESULTS: Among 292 studies identified, 21 met the inclusion criteria and were included. Of these studies, 9 reported that anxiety scores decreased after music interventions and 7 reported that pain could be decreased before, during, and after procedures. The methodology of the music intervention was important to the results on anxiety and pain in the clinical trials. More than 50% (13/21, 62%) of the studies included in this review allowed participants to select themes themselves. However, it was difficult to distinguish differences in effects depending on the device or software used for the music interventions. CONCLUSIONS: Technology-based music interventions could help reduce anxiety and pain among patients undergoing surgery or procedures. The findings of this review could help medical teams to choose a practical methodology for music interventions. Future studies should examine the effects of advanced technology-based music interventions using smart devices and software that promote interactions between medical staff and patients.

Eosinophils in hidradenitis suppurativa patients exhibit pro-inflammatory traits, implicating a potential pathogenic role in the disease.

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA+ eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.

Smoking Is Independently Associated with Increased Pain Severity and Interference in Patients with Traumatic Spinal Cord Injury.

Previous studies have shown a relationship between cigarette use and pain but never in the setting of traumatic spinal cord injury (TSCI). Therefore, the objectives of this study were to (1) determine whether smokers with TSCI experience increased pain compared with nonsmokers with TSCI and (2) determine whether smokers with TSCI experience worse functional outcomes than nonsmokers with TSCI. A retrospective analysis of the National Spinal Cord Injury Statistical Center database was performed. Pain severity, interference, and functional outcomes were compared between 514 nonsmokers and 124 smokers with American Spinal Injury Association (ASIA) C/D TSCI. Smokers reported higher scores for pain severity and interference compared with nonsmokers. These findings were significant on multivariable analysis. Smokers also reported higher rates of job loss compared with nonsmokers, but this finding was not significant on multivariable analysis. Smoking may be an independent risk factor for increased pain severity and interference in the setting of TSCI. (Journal of Surgical Orthopaedic Advances 33(2):103-107, 2024).

Aetiologies of Leg Pain among Patients Presenting to a Vascular Surgery Clinic.

OBJECTIVE: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023. METHODOLOGY: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma. RESULTS: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital. KEY WORDS: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

Cold therapy and pain relief after hot-iron disbudding in dairy calves.

Even when pain control is implemented, calves may experience pain for days after hot-iron disbudding. Whether calves seek pain relief post-disbudding offers a novel approach to assessing pain in these animals. By employing an approach-aversion paradigm, we explored the ability of cold therapy to provide immediate pain relief in disbudded calves. Calves were habituated to the manual placement of a cool or ambient pack on their forehead for a short duration simultaneous to milk reward consumption, prior to disbudding. Calves were then disbudded under local anaesthesia (procaine) and analgesia (meloxicam), and responses to the packs were observed over subsequent days. Individual calves were consistently exposed to either cool or ambient packs in different halves of a two-sided experimental pen, allowing for the testing of approach-aversion and conditioned place preference. We found calves approached milk rewards quicker and maintained contact for longer when receiving cold therapy compared to the ambient control. However, calves did not display any conditioned preference for the pen where they received the cool pack. These results add to the growing evidence of lasting pain following disbudding procedures and suggests that cold therapy provides some form of pain relief post-disbudding. Future studies should seek other ways to use cold therapy post-disbudding to reduce aversiveness and human involvement.