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

Background: Pulse dosing of high frequency spinal cord stimulation at 10 kHz (10 kHz SCS) may offer comparable clinical benefits as continuous 10 kHz SCS, but extreme pulse dosing (EPD) has not been studied.

Methods: Patients using an implantable pulse generator (IPG) with 10 kHz SCS to treat chronic back or leg pain were enrolled. After baseline assessments, patients underwent "EPD titration" starting at an EPD setting of 3%. Patients who preferred the EPD tried progressively lower EPD settings (0.6%, 0.3%, 0.14%, 0.06%), each for 7-10 days, until reaching an EPD they did not prefer over that previously tried. Patients were then followed up for 3 months at their lowest preferred EPD. All study visits included assessment of adverse events and patient-reported outcomes, including the numeric rating score (NRS) for pain intensity, Patient Global Impression of Change (PGIC), Oswestry Disability Index (ODI), and the PROMIS-SF for sleep disturbance. Device charging information was uploaded from the IPG at each visit.

Results: Eighteen patients completed testing (13 M/5 F; mean age, 61 years); 14 patients (78%) reporting a preferred EPD (at any setting) to standard 10 kHz SCS. Among 18 patients, the most common lowest preferred EPD was 0.14% (28%), followed by 0.06% (22%) and 3% (17%). All post-SCS pain scores were lower than pre-SCS pain scores (median NRS, 8.5 vs. 3.0; p = .004). For overall pain, NRS values did not vary significantly across timepoints after the pre-SCS period (median range, 3.0-4.0; p > .05). Similarly, patient satisfaction, PGIC, ODI, PCS, and PROMIS-SF scores for EPD did not vary significantly from those at baseline. Daily IPG recharge times were significantly shorter using the patient's lowest preferred EPD than at baseline (median minutes, 3.0 vs. 31.8; p = .0001).

Conclusions: EPD 10 kHz SCS may offer the same pain relief and quality-of-life benefits as standard 10 kHz SCS, while reducing recharge requirements and potentially lowering the risk of therapy habituation.

Introduction: This study evaluated the effects of low-intensity muscle contraction exercise on pain sensitivity, peripheral pathology, and central sensitization in the spinal dorsal horn in a rat model of end-stage knee osteoarthritis (OA) induced by monosodium iodoacetate (MIA).

Methods: Sixty-two male Wistar rats were assigned to three groups: OA, Exercise, and Sham. The Exercise group underwent quadriceps muscle contractions induced by electrical stimulation (50 Hz, 250 µs, 2-3 mA) with a duty cycle of 1:2 (2 s On, 4 s Off) for 20 min daily, five days per week, from day 29 to day 56 post-MIA administration. Pain sensitivity was assessed by measuring knee joint pressure pain thresholds (PPT) and paw withdrawal thresholds using von Frey filaments. Histological and immunohistochemical analyses of the knee joint and spinal cord included toluidine blue staining, tartrate-resistant acid phosphatase staining, and markers for CD68, CD11c, CD206, osteoclasts, nerve growth factor (NGF), calcitonin gene-related peptide (CGRP), and phosphorylated NR1 (pNR1).

Results: Knee joint PPTs were significantly higher in the Exercise group after day 35, accompanied by reductions in CD68-, CD11c-positive cells, NGF-positive cells, CGRP-positive fibers, osteoclasts, and pNR1-positive cells, as well as an increase in CD206-positive cells, compared to the OA group.

Discussion: Despite no significant changes in cartilage or subchondral bone degeneration, these findings suggest that low-intensity muscle contraction exercise alleviates pain sensitivity by modulating peripheral pathology and central sensitization. This study highlights the potential of therapeutic exercise as a strategy for OA pain management.

Classical trigeminal neuralgia (TN) is a severe chronic pain disorder characterized by sudden, intense facial pain attacks and represents a major burden for affected individuals. Microvascular decompression (MVD) can provide pain relief, yet not all patients benefit equally. A key challenge in selecting candidates for MVD lies in the limited predictive accuracy of current diagnostics, which mainly rely on subjective pain history and structural MRI findings. Since many asymptomatic individuals show neurovascular contact on imaging, its prognostic value remains limited. Electrophysiological measures, particularly cortical oscillations, may offer more objective insights into nociceptive system function. In this case series, we investigated 15 TN patients scheduled for MVD using magnetoencephalography prior to surgery to assess laser-evoked fields. Noxious stimuli were applied to the symptomatic and contralateral trigeminal dermatome. Ten patients achieved complete postoperative pain relief (responders), while five patients reported persistent symptoms (non-responders). Source reconstruction showed activation in the contralateral primary somatosensory cortex in all participants. Responders exhibited reduced low-frequency oscillatory activity at the pain site, whereas non-responders displayed increased activity in the same frequency band. Group-level analysis revealed distinct differences in oscillatory dynamics between responders and non-responders. These findings indicate altered cortical processing in TN and suggest that oscillatory activity patterns might serve as functional biomarkers. Incorporating these measures could improve preoperative stratification and guide treatment decisions for patients undergoing MVD.

In this perspective article we contend that acousmatic music, which departs from the traditional "instrumental music paradigm" by obscuring or removing the origin of sounds, may deepen a person's understanding and expression of pain and suffering, offering therapeutic potential. We propose that intentional engagement with acousmatic music can reshape listening habits, articulate and reframe the meaning of bodily and emotional experiences, and alleviate distressing sensations, feelings and thoughts. We propose that acousmatic music evokes memories of previous psychological traumas, such as painful events, and by doing so can prompt listeners to curiously explore the meaning and purpose of distressing symptoms. We argue that creative engagement with acousmatic music may allow individuals to express their somatic, emotional, and cognitive experiences, potentially leading to a deeper understanding of their living experiences. We discuss future directions for research and practice. We offer readers a stereo reduction excerpt of acousmatic music to facilitate an appreciation of the unusual nature of acousmatic music composition (https://soundcloud.com/nikos-stavropoulos/topophilia).

Objective: This study aimed to explore the perspectives of both patients and prescribers regarding analgesia after discharge following total hip or knee replacement surgeries, focusing on opioid use and the factors influencing patient and prescriber decision making.

Methods: Semi-structured interviews were conducted with 20 prescribers and 13 patients. 6 patients were interviewed before and after surgery. Thematic analysis of the data was conducted by three researchers.

Results: For prescribers, three key themes were identified: (1) A patchwork of prescribing practices with diverse influences on health professional's decisions, including the 'norm' of each site; (2) What counts as evidence for practice? in which prescribers relied on clinical experience, more than guidelines; And (3) Risk-benefit trade-offs that prescribers make when challenged to treat pain while minimising side effects. Analysis of patients' data also identified three key themes: (1) (Unfulfilled) expectations of careful pain management such as evidence-based decisions and close monitoring to avoid harm; (2) Risk-benefit trade-offs: fear of pain vs. fear of side effects including anxiety about both expected pain and expected side effects, and (3) Variation in self-management of opioid use due to varying interpretation of vague instructions. The views and expectations of prescribers and patients differ and sometimes conflict with each other.

Conclusion: This research highlights the need for improved guidance for both prescribers and patients, and clearer communication to optimise the management of pain after discharge.

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.