Pain Reports最新文献

Introduction: Ocular pain is a common complaint to eye care providers, associated with a variety of ocular conditions, among which dry eye disease (DED) is affecting millions of people worldwide. Despite being highly prevalent, ocular pain is not managed adequately in the clinic.

Objectives: The aim of this study was to investigate the analgesic potential of neurokinin-1 receptor (NK1R) antagonism in DED.

Methods: Dry eye disease was induced in mice, and an NK1R antagonist L-733,060 was topically administered twice daily throughout the study for 14 days. Hyperalgesia and allodynia were assessed using the eye-wiping test and palpebral ratio measurements. Corneas were collected for measuring substance P (SP) levels by enzyme-linked immunosorbent assay (ELISA) and imaging nerves by immunostaining. Trigeminal ganglions (TG) were collected to determine SP levels by ELISA and transient receptor potential cation channel subfamily V member 1 (TRPV1), transient receptor potential cation channel subfamily M (melastatin) member 8, c-Fos, and activating transcription factor 3 (ATF3) mRNA levels by real-time polymerase chain reaction.

Results: Treating DED mice with L-733,060 resulted in a significant reduction in eye wipe behavior, a significant increase in palpebral ratio, and significant decreases in SP levels in both the cornea and TG compared with the vehicle-treated group. In addition, NK1R antagonist treatment significantly suppressed the upregulation of TRPV1, ATF3, and c-Fos and prevented corneal nerve loss.

Conclusion: Neurokinin-1 receptor antagonism effectively reduced ocular nociception, decreased neuronal activation, and preserved corneal nerves in mice with DED. These findings suggest that blockade of SP signaling pathway is a promising therapeutic strategy for managing DED pain.

Chronic pain is a debilitating health problem affecting 20 million Americans annually. Most patients with chronic pain report negative impacts on daily function and quality of life, which can result in devastating emotional and financial stress. Although the causes of chronic pain remain elusive, there is increasing interest in sensitivity to everyday sensory stimuli as it relates to chronic pain, potentially serving as an indirect marker of altered central nervous system sensory processing. However, sensitivity to multiple sensory inputs, eg, bright lights, certain fabrics, loud noises, etc, is described using multiple terminologies. The lack of a common vocabulary makes it difficult to find and summarize related discoveries, potentially inhibiting scientific progress. Thus, the purpose of this scoping review was to identify and characterize the terminology used in publications assessing some form of multisensory sensitivity as it relates to pain (eg, a pain cohort or pain sensitivity). Our review of 6 databases (PubMed, Scopus, Embase, CINAHL, PsycINFO+, and Cochrane) comprehensively cataloged peer-reviewed studies published through March 2023 in this domain. Of 12,841 possible studies identified, 92 met all inclusion criteria, with over 80% being published in the last decade. A wide range of terminology has been used for this construct, likely in part a result of the many different professional disciplines represented. These results provide valuable insights for future development of a standardized vocabulary and serve as a resource to aid future investigators of multisensory sensitivity and pain in their study design.

Introduction: Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs.

Methods: The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed.

Perspectives: This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.

Introduction: Knowledge about long-time residual symptoms, disabilities, and psychological health in complex regional pain syndrome (CRPS) is limited.

Objectives: The aim was to evaluate outcome, focusing on physical symptoms, disability, and psychological health, in individuals with CRPS through a cross-sectional survey study.

Methods: Individuals with a confirmed diagnosis of CRPS were identified through medical charts and sent validated survey forms (Disabilities of the Arm, Shoulder and Hand-Quick version, Specific Hand Surgery Questionnaire-8 questions, EuroQol 5 Dimensions 3 levels, Life Satisfaction Questionnaire-11, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Sense of Coherence-29) and complementary questions.

Results: Responders (response rate: 99/238, 42%; CRPS type 1: 72%; CRPS type 2: 28%; time since diagnosis median: 59 [34-94] months) reported remaining symptoms and disability (Disabilities of the Arm, Shoulder and Hand-Quick version score: 45 [20-70]) and more improvement in type 1 than in type 2. Only 9% of individuals with CRPS reported no residual pain or discomfort. Approximately 60% had problems in daily activities, 49% had sleeping problems, and 90% experienced moderate-extreme pain with 23% still on sick leave. The Hospital Anxiety and Depression Scale survey revealed significantly higher scores than a Swedish reference population. Individuals with a low Sense of Coherence and high pain catastrophizing had worse disability and were less satisfied with their lives and physical and psychological health. A lower level of education and more anxiety were associated with worsened disability over time.

Conclusion: Individuals with CRPS suffer in the long term from pain, sleeping problems, and limitations in daily activities with occurrence of anxiety and depression, resulting in dissatisfaction with many aspects of their lives. A low Sense of Coherence and high pain catastrophizing are associated with a worse outcome. Biopsychosocial aspects should be addressed in clinical practice.

Introduction: Injection of recombinant human nerve growth factor (rhNGF) evokes acute heat and prolonged "polymodal" (mechanosensitive [CM]) and "silent" (mechanoinsensitive [CMi]) C-nociceptor sensitization. Both nociceptor classes can be activated differentially using slowly depolarizing electrical sinusoidal stimuli.

Objectives: To explore the temporal profile of nociceptor sensitization to heat and mechanical and electrical stimuli in humans after rhNGF.

Methods: Recombinant human nerve growth factor (1 µg) and NaCl (0.9%) was injected into human forearm skin (n = 9, 50 µL/injection). Pain ratings (numeric rating scale) to transcutaneous electrical stimuli (1 ms 20 Hz rectangular pulses, 500-ms half-period sine wave [1 Hz] and 4 Hz sine wave pulses [2.5 and 60 seconds]) were assessed at days 3, 21, and 49 after injection, in addition to heat pain thresholds (HPTs, 9 × 9 mm thermode) and mechanical impact pain (4 and 8 m/second).

Results: Suprathreshold sinusoidal stimulation for specific CM (1 Hz) and combined CM and CMi (4 Hz) activation resulted in enhanced pain from day 3 post rhNGF and lasted throughout 7 weeks. These temporal dynamics contrasted minimum HPTs at day 3 (normalized by day 49) or mechanical impact pain (developing slowly until day 21 before declining depending on stimulus intensity). Correlation analyses of electrical pain indicated diverging kinetics when assessed for CM with or without concomitant CMi activation at days 3 and 21, which converged 7 weeks post rhNGF.

Conclusions: Exceptionally long sensitization of CM and CMi nociceptors by rhNGF, uncovered by suprathreshold electrical sinusoidal stimulation, indicates a signal transduction-independent long-lasting hyperexcitability of C-nociceptors that clinically may contribute to rhNGF-maintained chronic inflammatory pain.

Introduction: Global prevalence of knee osteoarthritis is more than 300 million. Uncontrollable risk factors include age, sex, and height. Controllable risk factors include trauma, weight, and waist circumference.

Objectives: Our goal was to determine the association between knee osteoarthritis and anthropometric measures that include weight, height, and waist circumference.

Methods: Using 4,602 participants (45-79 years) from the Osteoarthritis Initiative, we analyzed the association between knee osteoarthritis and anthropometry collectively and by sex. We calculated female and male tertiles (3 groups) for anthropometry.

Results: Anthropometric measures were correlated with knee osteoarthritis (P ≤ 0.05) except the correlation between height and activities and height and quality of life. When comparing female weight tertiles, there were associations (P's < 0.001) between knee osteoarthritis and weight, but when comparing male weight tertiles, these associations were primarily between the lowest weight and highest weight groups. There were significant associations between knee osteoarthritis and height among female tertiles, with no differences among male tertiles. There were knee osteoarthritis/waist circumference tertile associations (P's < 0.001) for the lowest and highest waist circumference groups.

Conclusion: Higher weight in female participants was a stronger predictor of increases in knee osteoarthritis discomforts when compared to waist circumference, while weight and waist circumference were almost equivalent in predicting increases in knee osteoarthritis for male participants. Height did not predict increases in knee osteoarthritis with the exception of female symptoms and quality of life. Quality of life for both sexes was the most unfavorable with female participants reporting a more unfavorable quality of life than male participants.

Temporal summation of pain (TSP) is a human proxy for wind-up of dorsal horn neurons as assessed in animals. The common paradigm for eliciting TSP is evoked by repetitive nociceptive stimuli of equal intensity. Various stimulation and assessment protocols have been used. This scoping review aims to provide insight into key elements of TSP stimulation and assessment: modality, instruments, test location, familiarization, train characteristics, and calculations. PubMed, Embase, and Ebsco/CINAHL were searched for studies that measured TSP in adults with musculoskeletal conditions and healthy people. Four hundred six studies were included. Mechanical stimuli were the most commonly used modality (250 studies), followed by thermal stimuli (125 studies). Forty-six different instruments were used. Disregarding studies on widespread musculoskeletal pain and healthy participants, 40 studies evaluated TSP at painful sites, 77 in remote areas, and 66 in both locations. Of the 13 tested locations in patients, the hand (74 studies), lower leg (64 studies), and forearm (59 studies) were most commonly tested. A single practice round was the most common familiarization method (46 studies). Repeated stimuli were applied using 31 different frequencies (0.03-200 Hz) and sustained stimulations ranging from 5 to 1080 seconds were used. Twenty-two different train lengths, 63 different calculations (37 absolute, 19 relative, and 7 alternatives using data directly), and 14 different outcome measures (eg, self-reported pain rating scales and reflex thresholds) were used. Temporal summation of pain protocols vary excessively, hindering the comparison and pooling of results. None of the studies provided substantiation for their protocol choice.

Introduction: Chronic pain may negatively affect social functioning, but no study to date has examined the specific social impact of different chronic pain conditions in young women, and whether living with multiple chronic overlapping pain conditions (COPCs) differently influences social domains.

Objectives: This study aimed to assess social functioning (social isolation, hostility, informational support satisfaction, social roles, emotional support, friendships, and family relationships) among young women with chronic pain compared with pain-free controls and to test whether the number of COPCs influenced the extent of social burden.

Methods: Participants aged 18 to 30 years with a physician-confirmed diagnoses of migraine, fibromyalgia, or temporomandibular disorder (TMD) and pain-free controls were invited to participate from across the United States. After confirming eligibility, participants completed a 1-hour REDCap online questionnaire assessing social functioning.

Results: One hundred four participants (mean age 24.54 ± 3.35 years) were included (n = 26 with TMD, n = 25 with fibromyalgia, n = 25 with migraine, and n = 28 controls). All 3 chronic pain groups combined reported worse functioning than controls on friendship (P = 0.038), social isolation (P = 0.002), and social roles (P < 0.001). There were no differences on social variables between the 3 chronic pain groups (all P's > 0.05). Compared with those with 3 COPCs, participants with 1 condition reported better family relationships (P = 0.024).

Conclusions: Experience of chronic pain-regardless of the specific pain condition-may negatively affect some areas of social functioning in young women.

Introduction: Lumbosacral radiculopathy (LR), also known as sciatica, is a common type of radiating neurologic pain involving burning, tingling, and numbness in the lower extremities. It has an estimated lifetime prevalence as high as 43%.

Objectives: The objective of this randomized controlled trial was to evaluate the impact of virtually delivered Mindfulness-Oriented Recovery Enhancement (MORE) on patients with LR during the COVID-19 pandemic.

Methods: Potentially eligible patients were identified using electronic health record queries and phone screenings. Participants were then randomized to MORE or treatment-as-usual (TAU) for 8 weeks, with pain intensity assessed daily. At baseline and follow-up visits, participants completed questionnaires assessing the primary outcome, disability, as well as quality of life, depression, mindful reinterpretation of pain, and trait mindfulness.

Results: In our study, patients undergoing virtual delivery of MORE had greater improvements in daily pain intensity (P = 0.002) but not in disability (P = 0.09), depression (P = 0.26), or quality of life (P = 0.99 and P = 0.89, SF-12 physical and mental component scores, respectively), relative to TAU patients. In addition, patients in MORE experienced significantly greater increases in mindful reinterpretation of pain (P = 0.029) and trait mindfulness (P = 0.035).

Conclusion: Among patients with lumbar radiculopathy, MORE significantly reduced daily pain intensity but did not decrease disability or depression symptoms. Given the long duration of symptoms in our sample, we hypothesize the discrepancy between changes in daily pain intensity and disability is due to fear avoidance behaviors common in patients with chronic pain. As the first trial of a mindfulness intervention in patients with LR, these findings should inform future integrative approaches to LR treatment, particularly when considering the increasing use of virtual interventions throughout the COVID-19 pandemic.

Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI -0.13 to 0.32). We could not document differences between TCA and serotonin-noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.