Frontiers in pain research (Lausanne, Switzerland)最新文献

The majority of patients with acute pain experience sleep disturbances that persist despite analgesic treatments such as mu opioid receptor (MOP) agonists and non-steroidal anti-inflammatory drugs (NSAIDs). Further, sleep disturbances increase pain sensitivity, demonstrating a bi-directional relationship between pain and sleep. Given that commonly prescribed MOP agonists disrupt sleep in pain-naïve subjects, it is possible that analgesics exacerbate sleep disturbances associated with pain states. Thus, pain-induced sleep disturbances remain an understudied and undertreated symptom impacting overall quality of life for which development of novel analgesics is critical. Nociceptin/Orphanin FQ opioid receptor (NOP) agonists have shown promise as a novel class of analgesic, and, given sleep-promoting effects in naïve subjects, may improve pain-induced sleep disturbances. We examined the effects of intraperitoneal lactic acid administration, a noxious stimulus which produces acute abdominal pain, on sleep alone and in the presence of analgesics morphine (MOP agonist), meloxicam (NSAID), and novel NOP agonist AT-403. Male and female Sprague Dawley rats were implanted with wireless electroencephalography (EEG) devices to assess sleep duration and brain function using quantitative EEG analyses. Lactic acid dose-dependently decreased rapid eye movement (REM) and non-REM (NREM) sleep duration, and, consistent with prior studies, increased stretching and decreased rearing and grooming behaviors in a concentration-dependent manner. Morphine significantly decreased NREM and REM sleep in pain-naïve states and did not improve sleep following lactic acid administration. Additionally, lower doses of morphine increased high frequency power spectra. In contrast, meloxicam did not affect sleep or quantitative EEG in pain-naïve rats, nor alter lactic-acid induced effects. AT-403 increased NREM sleep duration and slow wave activity during NREM sleep, decreased NREM sleep latency and REM sleep duration both alone and in the presence of lactic acid; at the higher doses tested, AT-403 shifted relative spectral distribution from higher to lower frequency ranges, indicative of a sedative effect. In contrast, AT-403 attenuated lactic acid-induced behaviors and promoted sleep at doses that did not decrease locomotor function. Together, these data demonstrate that current analgesics do not sufficiently alleviate acute pain-induced sleep disturbances whereas NOP agonists represent a novel mechanism for the potential treatment of pain-induced sleep disturbances.

Introduction: Older adults represent a growing proportion of individuals with opioid use disorder (OUD) and adults 55 + are significantly more likely to experience a fatal overdose. This exploratory pilot study examined age-related differences in health and treatment characteristics among patients in outpatient opioid treatment to assess whether older adults show distinct patterns compared to younger patients, providing insight into this growing population.

Methods: This retrospective chart review analyzed data from 79 patients (ages 23-70) seeking care at a low-threshold outpatient opioid treatment clinic. Data were extracted from electronic health records and included demographics, substance use, diagnoses, current pain, depression, quality of life, and treatment characteristics. Associations between age and clinical variables were analyzed using correlational, logistic regression, and repeated-measures ANCOVA methods.

Results: Older age was predictive of past pain-related diagnoses and older adults (55+) longer histories of illicit opioid use (mean = 30 years) and tobacco smoking (mean = 43 years) compared to younger adults. While polysubstance use was more common among younger patients, fentanyl use was high across all ages (∼65%). Older adults received higher methadone doses and remained in treatment longer. Despite greater chronic exposure to opioids, age was not significantly associated with depression or quality of life scores at intake.

Conclusions: Findings from this pilot study reveal age-related patterns in substance use, pain history, and treatment engagement among patients with OUD. The data suggest that older adults may face unique risks related to cumulative opioid exposure, while also demonstrating potential protective factors such as treatment retention. Integrated, age-responsive approaches are urgently needed to address the complex needs of this growing population.

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating urologic chronic pelvic pain condition characterized by pelvic pain and urinary symptoms. Evidence suggests that in chronic pain conditions such as IC/BPS, inflammatory markers are associated with heightened symptom severity and widespread pain. Non-pharmacological treatments such as cognitive-behavioral therapy are recommended as a core component of IC/BPS treatment. There is limited and mixed evidence as to whether inflammatory markers are affected by non-pharmacological treatments or their relationship to treatment response. This exploratory study considered how inflammatory characteristics may both predict and explain treatment response in a sample of females with interstitial cystitis.

Method: Participants were randomized to receive either 8-weeks of telemedicine-delivered cognitive-behavioral therapy (CBT) or an active attention control. Six cytokine/chemokines in whole blood plasma (IL-6, IL-8, IL-10, IL-1β, and TNF-α) were assessed in a subset of trial participants at baseline, post-treatment, and at five months. We assessed relationships between baseline plasma inflammatory cytokine levels and self-reported symptoms, changes in cytokines over time, and how baseline cytokine levels may relate to clinically meaningful indicators of change following CBT.

Results: Cytokine/chemokine levels did not significantly change over time. Higher levels of unstimulated IL-1β were associated with significantly worse clinical pain characteristics and greater degree of CBT treatment response.

Discussion: This suggests that individuals with greater degrees of inflammation may derive more benefit from the self-regulation training, pain coping strategies, and cognitive reframing offered in CBT for pain.

Introduction: Musculoskeletal pain is highly prevalent among older adults and a leading cause of disability. Digital health promises to deliver timely and quality care, but existing reviews fail to be specific for older adults, focus on a single type of technology or a single body site, and do not provide an integrated overview of the effectiveness of current digital interventions. This systematic review with meta-analysis (Prospero ID: CRD42024549668) aimed to assess the effectiveness of digital interventions for pain management in reducing pain intensity and self-reported disability in older adults with musculoskeletal pain.

Methods: We searched PubMed, Web of Science, Scopus, and Academic Search Complete from inception to April 2025; extracted data on participants, interventions, and primary (pain intensity and self-reported disability) and secondary outcomes (performance, pain-related psychological variables, and adverse events).

Results: Thirty-six RCTs were included (n = 4,041). Compared to other active interventions, older adults who received digital pain management reported lower pain intensity (SMD = -0.23, 95%CI = -0.37;-0.09) and lower self-reported disability (SMD = -0.22, 95%CI = -0.39;-0.04) at post-intervention. The effect was maintained at 6 months for pain intensity (SMD = -0.20; 95%CI = -0.38;-0.03), but not for disability (SMD = 0.13, 95%CI = -0.38;0.63). The certainty of evidence was low or very low, and heterogeneity was low to substantial. Most studies included domains judged as high risk of bias.

Discussion: The evidence is very uncertain on the effect of digital interventions on pain intensity and disability. They may decrease pain intensity and disability similarly to other interventions, but more research is needed to investigate the effect of digital interventions and identify key aspects that maximise the intervention.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024549668, PROSPERO CRD42024549668.

Background: Low back pain (LBP) uses a large proportion of health care resources. Data are needed for health care planning, measuring adherence to guidelines for quality assurance, and assessing overuse and underuse of health care services. The aim of this review is to summarize claims data and describe trends in health care utilization for LBP for the years 2000 to 2020.

Methods: This scoping review summarizes studies and health reports using claims data of people aged ≥15 years covered by a statutory health insurance in Germany for the period 2000 to 2020. We searched publications in PubMed, EMBASE and Google. Data on health care services were extracted and trends over the years were summarized.

Results: We included data from 76 publications, health reports and online databases. Every year, 25 to 32% of adults in Germany seek care for LBP. Most of the claims data cannot be pooled because of differences in standardization and reporting. However, trends are observable. Magnetic resonance imaging increased to 7.5%, plain radiography decreased to 15%. The number of sick leave days decreased slightly over time. Hospital admissions for LBP, spinal surgery, and opioid use increased. Outpatient rehabilitation increased, but the overall use of rehabilitation services remained relatively stable.

Conclusions: Inconsistent reporting standards and fragmentation of German claims data reporting, hinders a comprehensive understanding of health service utilization for low back pain. Despite limitations, current data suggest potential overuse of resources for LBP in Germany, consistently with international data. Given the high proportion of patients consulting for LBP better monitoring of health service utilization is needed to improve quality of care and resource allocation.

Purpose: Low back pain is difficult to study due to its heterogeneity. Inducing back pain experimentally, with an established model such as heat-capsaicin, would beneficially control for some variability. How heat-capsaicin affects neurophysiological factors relevant to back pain is currently unknown, therefore, this study used a randomized crossover design with the aim to explore the differences between heat-capsaicin and placebo on brain activity and blood markers.

Methods: 18 healthy participants completed two sessions: heat-capsaicin (45°C heat + capsaicin) and placebo (reduced heat + placebo). Pre- and post-pain-induction/placebo, electroencephalogram and blood draws were taken, and perceived pain was rated with a 100 m visual analog scale. Band power was calculated for theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), gamma1 (30-58 Hz), and gamma2 (62-100 Hz) for six brain regions. An immune assay was run on plasma in duplicate for cytokines IL-1β, IL-6, IL-10, and TNFα. A repeated measures ANCOVA was run for all variables comparing between conditions (heat-capsaicin, placebo) with baseline measures as covariates. A Pearson's correlation was used to determine the relationship between perceived pain ratings and brain wave and blood biomarkers.

Results: The heat-capsaicin model induced transient mild to moderate pain which was significantly higher than placebo (24.50 vs. 0.39; p < 0.001). Brain wave and blood biomarkers were not significantly different between heat-capsaicin and placebo (p ≥ 0.05) or correlated to perceived pain ratings (p ≥ 0.15).

Conclusion: Levels of perceived pain did not relate to neurophysiological changes that may occur immediately after heat-capsaicin exposure. Although changes have been found with other pain models and clinical low back pain, a statistically significant systematic response was not measurable using blood cytokine markers immediately after pain induction and may take longer to develop.

Chronic musculoskeletal (MSK) pain can be characterized by its temporal variability and evolution, affecting both pain management and treatment outcomes. While pain variability is traditionally studied over long timescales (e.g. days or weeks), few studies have explored short-term fluctuations (e.g. minutes to seconds) and their clinical relevance. This study investigated the short-term variability of chronic musculoskeletal pain across consecutive days, examining whether these fluctuations are stable, exhibit consistent temporal patterns, and relate to clinical severity. We also explored whether individuals with chronic MSK pain could predict their pain intensity on the following day, suggesting an ability to learn about their pain's levels. Eighty-one participants with chronic MSK pain to the back, neck, leg or arm (22-65 years, 72% females, 28% males) rated their pain continuously over two days, using a smartphone-based app. Results indicated that pain ratings were stable and exhibited consistent temporal patterns across days, with a temporally correlated structure. High mean pain levels were associated with lower variability, possibly reflecting a stabilized pain state. Short-term pain variability negatively correlated with clinical severity, indicating that greater variability is linked to milder pain. These findings highlight the importance of short-term variability as a distinct and clinically relevant feature of chronic MSK pain, with implications for personalized pain management strategies.

Quantitative pain assessment is important for effective pain management. Pain pressure threshold (PPT) and Pain Tolerance (PT) measured through pressure algometry offer valuable tools for quantitative evaluation of nociceptive stimuli. Low-cost algometers, described in literature require complex calibration and lack a digital interface, limiting real-time data acquisition and integration with electronic health record systems. In the current study, we developed a durable and accurate pressure algometer built on the base of a syringe, an Arduino microcontroller and an analog piezoelectric pressure sensor. The PPT values obtained with our device are in good correlation with data obtained utilizing commercially available digital and mechanical algometers. In addition, our device can be easily connected to a computer via a USB, allowing for convenient data storage and analysis. Our results demonstrate the accuracy and reliability of a novel algometry device constructed from readily available materials and requires minimal engineering and programming skills.