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

Background: Several studies have demonstrated that veterinarians hold breed-specific beliefs about canine pain sensitivity. However, it remains unknown whether these beliefs impact how veterinarians recognize and treat pain in a clinical setting. Therefore, the objective of this study was to determine if there were differences in the assessment and treatment of pain across patients admitted to a veterinary emergency room (ER) from different breeds.

Methods: Veterinary ER records were retrospectively analyzed to evaluate the effects of breed on the assessment and treatment of pain in canine patients admitted to a single academic ER over a two-year period. Extracted data included patient signalment and information documented in medical evaluations completed by ER clinicians.

Results: The final sample included records from 3,744 patients across 69 breeds/breed types. Patient breed and the service the patient was transferred to from the ER were significantly explanatory for differences observed in pain scores and pain management plans assigned. The effect of breed and transfer service remained robust when accounting for covariates.

Conclusions and clinical relevance: Certain breeds were assigned pain scores lower than average, while other breeds were assigned higher than average pain scores despite a lack of evidence that these breeds presented with less or more painful conditions. As breed-specific beliefs do not align with experimental measures of pain sensitivity, the present findings have implications to help refine pain education and medical decision-making and ultimately improve patient care.

Objective: Non-odontogenic toothache, which is characterized by tooth pain without corresponding dental abnormality, is occasionally indeterminate due to its complicated persistent teeth, dentoalveolar and/or facial pain, specifically between patients with persistent idiopathic dentoalveolar pain (PIDAP) and those with trigeminal neuralgia (TN), accompanied by atypical sensations. This study aimed to clarify clinical characteristics in this patient population and to identify clinical real-world factors for differentiation.

Methods: All clinical data were retrospectively collected. Totally 340 patients, who were referred to our department with undiagnosed complicated persistent pain, were involved in the comparative analysis, depending on symptoms' laterality, and 149 patients with unilateral symptoms were involved, depending on the presence of neurovascular compression (NVC) of trigeminal nerves and final diagnosis of PIDAP or TN.

Results: Patients with bilateral symptoms (n = 105) presented more severe affected pain sensations with higher pain catastrophizing compared to patients with unilateral symptoms (n = 234, p = 0.022). NVC was observed in 84 patients (56.4%); however, no significant difference in clinical features was observed depending on the presence of NVC. While patients with TN (n = 26) presented significantly stronger "shooting" and "stabbing" pain (p = 0.004, p = 0.006, respectively) with more severe NVC condition (p = 0.033), patients with PIDAP (n = 123) showed significantly higher scores in the central sensitization inventory (p < 0.001) and somatic symptom scales-8 (p = 0.004).

Conclusion: These results suggest that relying solely on examining the presence of NVC is insufficient to distinguish PIDAP and TN in this patient population, but careful assessment of pain quality, pain catastrophizing, central sensitization, and somatic symptoms, besides detailed neurovascular conditions, is crucial.

Pain resulting from tissue damage, including surgical incision, is often only partially responsive to anti-inflammatory drugs, suggesting the contribution of a neuropathic mechanism. Tissue damage leads to expression in dorsal root ganglion (DRG) sensory neurons of activating transcription factor 3 (Atf3), a known injury-induced transcription factor. Atf3 expression is associated with sensitization of cellular physiology and enhanced amplitude/duration of a nociceptive reflex. It is unclear how tissue damage leads to these changes in the sensory neurons, but it could include direct damage to the tissue-innervating axons and inflammation-associated retrograde biochemical signalling. We examined the necessity and sufficiency of incision, inflammation, and axonal conduction for induction of Atf3 in response to skin incision in rat. Incision outside of a single dermatome, but close enough to induce inflammation inside the dermatome, was not sufficient to induce Atf3 expression in the corresponding DRG. Incision inside the dermatome led to strong expression of Atf3. An anti-inflammatory drug did not prevent this induction of Atf3. In a mouse model of repeated injury - a major etiological factor for chronic pain - a second plantar incision induced a significant extension in the duration of mechanical hypersensitivity as compared to a single plantar incision. This corresponded with a remarkable increase in Atf3 expression in a rat model of repeated incision. Together, these results suggest that damage to axons innervating the skin is both necessary and sufficient for induction of Atf3 expression in sensory neurons. This is dramatically increased by repeated injury. Further, pre-treatment of the nerves innervating the incised skin with bupivacaine, a local anesthetic commonly used to reduce surgical pain, did not prevent induction of Atf3, indicating that conduction of action potentials is not necessary for induction of Atf3. Closure of incision with surgical glue or treatment with polyethylene glycol, known to enhance membrane integrity after injury, reduced incision-associated regulation of Atf3, Growth-Associated Protein-43 (Gap43), and electrophysiological changes. We conclude that tissue damage-induced pain arises from a mix of Atf3-independent inflammation-related mechanisms and axonal damage-associated mechanisms and therefore requires a mix of approaches to prevent/treat persistent post-surgical pain.

Chronic pain patients (CPPs) often face complex, multifactorial challenges, with many reporting that their pain management lacks comprehensiveness. Spiritual care has emerged as a potential resource in addressing the diverse needs of CPPs, but remains underutilized due to healthcare professionals' (HCPs) uncertainty about how to integrate it into clinical practice. This study aimed to develop a best practice guide for integrating spiritual care into chronic pain therapy using a qualitative Delphi study. Three rounds of data collection, involving a panel of CPPs and HCPs with expertise in chronic pain from various disciplines, were conducted. Participants shared their experiences and suggestions for addressing spiritual aspects in pain therapy. The process led to the formulation of a consensus-based best practice guide, outlining practical strategies for HCPs to engage with spiritual care in a way that is respectful and sensitive to individual patient needs. Results indicated that incorporating spiritual care in chronic pain therapy can enhance therapeutic relationships, foster more meaningful patient interactions, and provide additional coping mechanisms. The guide was rated as clinically applicable, and offers a structured yet flexible framework for integrating spiritual care into multimodal pain treatment and is expected to improve patient outcomes by addressing existential aspects of chronic pain.

Objective: This study aimed to evaluate the effectiveness of ultrasound-guided acupotomy (UgA) in treating Cervical spondylosis (CS), particularly in pain relief, improvement in cervical range of motion (CROM), and overall clinical efficacy, through a systematic review and meta-analysis based on GRADE quality assessment.

Methods: Following PRISMA guidelines, we searched databases including PubMed, Embase, Cochrane Library, Web of Science, and CNKI, Wanfang, Weipu, and Sinomed, identifying 33 randomized controlled trials (RCTs). Inclusion criteria were: patients aged 18-70 with a diagnosis of CS, intervention with UgA, and control groups receiving placebo, physical therapy, or other conventional treatments. Primary outcomes included clinical effective rate and Visual Analog Scale (VAS) for pain, while secondary outcomes encompassed Neck Disability Index (NDI), CROM, and mean flow velocity of vertebral and basilar arteries (MFV-VA/BA). Study quality was assessed using the Cochrane Risk of Bias 2.0 tool, and meta-analysis was conducted using Stata 15.0. The GRADE approach was used to evaluate evidence quality.

Results: Meta-analysis revealed that UgA significantly improved the clinical effective rate compared to control treatments (RR = 1.17, 95% CI: 1.13-1.21), with low heterogeneity (I ² = 12%). UgA also demonstrated significant pain reduction (WMD = -0.96, 95% CI: -1.25 to -0.67), albeit with high heterogeneity (I ² = 91.6%). For secondary outcomes such as NDI, CROM, and MFV-VA/BA, UgA showed moderate improvements, but with considerable heterogeneity. GRADE assessment indicated high-quality evidence for the clinical effective rate, while evidence for VAS, NDI, and CROM was rated as low or very low due to heterogeneity and publication bias.

Conclusion: UgA shows superior efficacy for pain and disability in cervical spondylosis compared to non-UgA and other acupuncture related therapies. However, heterogeneity and potential publication bias exist. It requires skilled practitioners and real-time ultrasound guidance for treatment. Future multinational randomized trials with standardized protocols are needed.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/PROSPERO, PROSPERO CRD42025649835.

Conditioned pain modulation (CPM) is a behavioral measure of diffuse noxious inhibitory control (DNIC), an endogenous central pain modulatory mechanism in which one pain stimulus suppresses the perception of another. CPM efficiency is reduced in individuals with chronic pain and serves as a potential predictor for the development of chronic pain conditions. Current research indicates that CPM, traditionally viewed as a static metric, may exhibit protocol-dependent variability in its effects on pain sensitivity, potentially through neuroplastic mechanisms and central pain processing pathways. This randomized controlled trial (NCT05783362) investigated whether repeated activation of central pain modulatory systems enhances CPM efficiency. The secondary aim examined associations between repeated CPM exposure and pain-related psychological factors. Sixty healthy participants (52% female; ages 18-75) were randomly allocated to High Exposure (HE), Low Exposure (LE), or No Exposure (NE) CPM intervention groups. Pre- and post-intervention measures included CPM efficiency and pain sensitivity across thermal and pressure pain tests. Two-way ANOVA analyses revealed significant main effects for both time (p < 0.001, η ² = 0.23) and intervention (p = 0.030, η ² = 0.107) on CPM efficiency when comparing HE and LE groups from pre- to post-intervention. One-way ANOVA analysis at the final visit showed that HE demonstrated significantly higher CPM efficiency compared to LE (p = 0.02, Cohen's d = 0.73), while comparisons between HE and NE approached but did not reach statistical significance (p = 0.053-0.060; medium-to-large effect sizes, Cohen's d > 0.70). This was supported by increased heat threshold pain intensity ratings (p < 0.001, η ² = 0.13), suggesting broader adaptations in pain processing that strengthen descending pain control mechanisms. Other QST measures and psychological variables remained unchanged, suggesting the specificity of the modulatory enhancement. Results support the plasticity of endogenous pain modulation and suggest potential therapeutic applications for pain management interventions.

Clinical trial registration: https://clinicaltrials.gov/study/NCT05783362, identifier NCT05783362.

Background: Neck pain (NP) represents a significant global health challenge, with a considerable proportion of individuals enduring persistent NP, which is associated with psychological stress. However, it remains unclear whether stress acts as a prognostic factor or emerges as a consequence of ongoing pain. An individual's behavioral response to pain, known as activity patterns (eustress persistence, distress persistence, activity pacing, and fear avoidance), reflects how individuals engage in daily activities and may influence both the experience and course of pain. These patterns have been linked to stress, potentially exacerbating pain intensity and disability. This study aims to investigate the prognostic value of activity patterns, subjective and objective stress in acute NP after three months. Furthermore, it examines the relationship between subjective and objective stress measures.

Methods: This study included participants (n = 125) with acute neck pain (NP) (<4 weeks). Baseline stress levels were measured objectively using hair cortisol concentration and subjectively using the Stress and Coping Inventory (SCI). Activity patterns were identified using the Avoidance-Endurance Fast Screen (AE-FS). Linear mixed models (LMM) were used to assess whether stress and activity patterns during the acute phase were prognostic factors for pain and disability three months later. A Pearson correlation was calculated between the subjective and objective stress measures.

Results: Weak correlations were found between subjective and objective stress measures. In the LMM, higher pain intensity during the acute NP phase was associated with increased pain intensity at 3-month follow-up. In terms of disability, both initial pain intensity and "stress due to uncertainty" were associated with higher disability after three months.

Discussion: Only a few consistent prognostic factors for persistent pain and disability have been identified, raising the question of whether current measures capture the most relevant aspects.Clinical Trial Registration: https://www.clinicaltrials.gov published 07/22, identifiers NCT05468684.

Introduction: Peripheral neuropathy (PN) may cause severe, treatment-resistant pain, especially in traumatic and/or iatrogenic cases. In those with insufficient responses to conventional strategies, spinal cord stimulation (SCS) may be a useful treatment option. However, limited research has been performed on SCS for this indication. This study aims to assess the efficacy, satisfaction and safety of SCS in patients with PN caused by traumatic and/or iatrogenic factors.

Methods: Patients with traumatic and/or iatrogenic PN, implanted with SCS between 2005 and 2021 at Radboudumc are included in this study. Perioperative data on efficacy, satisfaction, and safety were retrospectively collected from the electronic patient records (EPIC) and analyzed using descriptive statistics. The efficacy is assessed with the numeric rating score (NRS). Responders are defined as those having ≥50% reduction in NRS.

Results: Fifteen patients (M = 8, 48 ± 12 years) are included. At last follow-up (2-18 years), 63% (10/15) of patients are defined responders with an average decrease in NRS of 63% (8.1 ± 0.8 to 3.0 ± 2.0) (p < 0.01). All patients are satisfied with their implant. A complication was present in one patient, reporting a superficial infection (6%, 1/15) following implantation.

Discussion: Unlike peripheral nerve stimulation (PNS) and dorsal root ganglion (DRG) stimulation, which are more frequently considered for patients with PN caused by traumatic and/or iatrogenic factors, SCS enables central nervous system stimulation via the spinal cord, thus targeting pain regions associated with multiple lower limb nerve roots. As PN, caused by trauma and/or iatrogenic factors may affect multiple nerves simultaneously, it is suggested that SCS offers improved clinical benefit for these patients.

Conclusion: The current study demonstrates that SCS is a promising treatment modality for patients with traumatic and/or iatrogenic PN. Prospective trials comparing SCS to treatments like PNS and DRG stimulation are essential to substantiate its efficacy, expand its indications, and inform future clinical guidelines for patients with intractable traumatic or iatrogenic peripheral neuropathy.

Background: Although interest in migraine has increased in recent years, important gaps remain in understanding and optimizing its management. These gaps are particularly pronounced in pediatric migraine, which continues to be understudied.

Case report: This case report demonstrates the efficacy and safety of transcutaneous auricular vagus nerve stimulation (taVNS) in an 8-year-old male patient with refractory chronic migraine with aura [two to three weekly episodes; visual analog scale (VAS): 5-9; duration of each episode was 24 h]. After discontinuing all prophylactic and abortive medications (except ibuprofen suspensions such as Motrin®), the patient underwent a 28-week taVNS protocol that involved the following phases: a 4-week acute intervention, a 4-week intermission period, a 12-week preventive intervention, and an 8-week follow-up. During the acute intervention phase, the patient's headache duration decreased by 84.4%, and frequency was reduced to fewer than two episodes/week, with complete aura resolution. The preventive intervention yielded further improvement to fewer than 1 episode/week by week 8 (with a 37.5% reduction in medication use). At final follow-up, the patient maintained a medication-free status with only three mild episodes (VAS: 1-3; duration <30 min) in the last 4 weeks. No adverse events were observed.

Conclusion: taVNS was effective and safe in the management of chronic migraine in the reported pediatric patient. These findings suggest the need for further evaluation of this non-pharmacological intervention in pediatric migraine.

Background: Headache is a common adverse drug reaction (ADR) across diverse therapeutic classes, yet systematic evaluations of drug-associated headaches in real-world settings are limited. This study aimed to explore the association between various medications and the reporting of headache as an ADR using the FDA-Adverse Event Reporting System (FAERS).

Methods: We conducted a retrospective disproportionality analysis using FAERS data from Q1-2018 to Q4-2024. Duplicate reports were removed per FDA guidelines. Reports with headache as an adverse event and drugs classified as Primary Suspect were included. Disproportionality metrics - Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR)-were calculated to identify signals. Drugs were classified according to the Anatomical Therapeutic Chemical(ATC) classification system, and time-to-onset analyses were performed.

Results: A total of 313,166 headache-associated cases were identified. Females (66.66%) and patients aged 51-65 years (21.35%) were most commonly affected. The drugs with the highest headache risk based on ROR included glecaprevir/pibrentasvir (ROR = 10.445), sofosbuvir/velpatasvir (ROR = 9.729), and eptinezumab-jjmr (ROR = 6.775). Top frequently reported drugs were apremilast, treprostinil, and adalimumab. Calcium homeostasis agents (ROR = 6.268) and systemic antivirals (ROR = 4.259) emerged as the ATC classes with the highest headache signal strength. Early-onset headaches (≤7days) were particularly associated with ofatumumab and fingolimod. Late-onset headaches (>90days) were linked to treprostinil and infliximab-dyyb.

Conclusion: This large-scale pharmacovigilance study identifies multiple drugs and therapeutic classes with significant associations to headache as an ADR. These findings highlight the need for proactive headache monitoring, particularly during early treatment phases, and warrant further prospective investigations to understand mechanisms and preventive strategies.