In recent years, studies have suggested an epigenetic fingerprint related to specific diseases and pathological conditions characterised by itch. Epigenetics, defined as modifications that regulate gene expression without altering the DNA sequence, has previously been shown to be involved in pain, but its association with itch remains poorly investigated. This review aims to summarise the current knowledge regarding the involvement of epigenetic modifications in preclinical models and clinical dermatological itch conditions.
English-language studies were identified through PubMed and Google Scholar using Medical Subject Heading (MeSH) terms related to itch or pruritus and epigenetics or DNA methylation or histone modification or microRNA or lncRNA or circRNA or non-coding RNA, from inception to January 2025. Non-relevant publications and non-peer-reviewed formats were excluded. Reference lists were also screened for additional studies.
Both preclinical and clinical studies indicate that DNA methylation is involved in the regulation of itch in atopic dermatitis and other pruritic skin conditions, and histone deacetylase inhibitors have the effect of alleviating pruritus. Among miR-711, miR-203b-3p, and miR-let-7b, identified as mediators of itch in animal models, miR-711 and miR-203 were also upregulated in certain clinical models.
A clear association between itch and epigenetic modifications has been demonstrated in both preclinical skin disease models and clinical dermatological conditions. Several of these changes appear consistently across experimental and human studies, suggesting their role as shared molecular regulators of itch.
Current understanding of the underlying mechanisms of itch remains limited, and optimal treatments for chronic itch have been difficult to develop. Epigenetic modifications in the pathophysiology of itch may contribute to our understanding of itch pathways and pave the way for new, potential treatments.
Pain, fear, and motor function are interrelated. This study aimed to clarify their causal relationships by examining longitudinal changes from the preoperative to the acute postoperative period after total knee arthroplasty (TKA).
This exploratory prospective observational study included 27 inpatients (mean age, 74.1 years [SD = 9.9]; 40 knees). Pain, fear and motor function were assessed preoperatively and 1 and 2 weeks postoperatively. At each time point, rest pain, motion pain, fear of motion, and kinematic parameters of knee movement (velocity, angle, surplus null and spectral entropy) were measured. The cross-lagged panel model was used to estimate causal relationships.
Longitudinal analysis revealed that reduced movement at 1 week predicted greater rest pain at 2 weeks, and higher rest pain at 1 week predicted more excessive movement irregularity at 2 weeks. Models including preoperative factors did not meet the goodness-of-fit criteria and were therefore excluded.
Pain and motor function predicted each other through distinct factors and pathways during the acute postoperative recovery period after TKA. These interactions may contribute to persistent pain and functional limitations, highlighting the need for targeted early interventions.
Understanding the temporal relationships between acute postoperative pain and knee kinematics may provide insights into the mechanisms underlying prolonged recovery.
Excessive behavioural avoidance in the acute postoperative period may be involved in prolonged pain and motor dysfunction after total knee arthroplasty. In this study, longitudinal analysis of pain, fear, and motor impairment (behaviour) was conducted using a cross lagged panel model. Decreased range of motion in the acute phase predicted delayed pain recovery, whereas pain intensity predicted awkward movement. These results may indicate specific problems that should be addressed in the early postoperative period.
Frozen shoulder (FS) has long been considered a localised musculoskeletal disorder, yet FS often involves widespread pain, suggesting central sensory dysregulation. While pressure pain threshold (PPT) assesses mechanical sensitivity, electrical measures such as current perception threshold (CPT) and electrical pain threshold (EPT) may capture various sensory alterations but are rarely applied in FS.
To map somatosensory alterations in unilateral FS by comparing PPT, CPT, and EPT across multiple regions with matched healthy controls (HC).
37 unilateral FS participants and 35 matched HCs underwent PPT, CPT, and EPT measurements at lateral deltoid (LD), medial forearm (MF), cervical spine (CS), and lumbar spine (LS). Bilateral LD and MF were tested in FS participants. Between-group and regional differences were analysed using linear mixed models, and correlations with pain intensity were examined.
FS participants exhibited significantly reduced PPT across all sites (d = 1.27–4.55) and increased CPT and EPT at affected LD and CS regions (d = 2.89–4.92). Electrical thresholds were higher over CS than LS in the FS group, whereas the opposite pattern appeared in the HC group. EPT correlated with PPT (ρ = 0.54), and both were negatively associated with pain intensity (ρ = −0.72 and −0.69, p < 0.001).
FS demonstrates mechanical hyperalgesia and electrical hypoesthesia, indicating central neuroplastic changes beyond the affected shoulder.
This study integrates electrical and mechanical sensory testing, revealing multimodal evidence of central sensitization in FS and offering novel quantitative markers to guide individualised pain assessment and rehabilitation.
ClinicalTrials.gov identifier: ChiCTR2400086393
Aerobic exercise leads to transient hypoalgesia, but little is known about these effects over extended periods. This study aimed to investigate exercise-induced hypoalgesia (EIH) responses in healthy individuals during long-distance running on a treadmill.
Thirty healthy participants (18–50 years) completed a 15 km treadmill run. Pain sensitivity was assessed using pain pressure threshold (PPT) before and during the run. Additionally, cuff-PPT (cPPT), cuff-pressure pain tolerance threshold (cPTT), temporal summation of pain (TSP) and conditioned pain modulation (CPM) were assessed with pressure cuff algometry before and during the run. Data were analysed using repeated measures ANOVA. Exploratory subgroups, based on changes in PPT, were identified using latent growth mixture models, and logistic regression was used to predict subgroup membership.
No significant changes were observed over time for PPT, PTT, cPPT or CPM at the group level. TSP decreased significantly after 10 and 15 km (p ≤ 0.004) when compared to baseline. Exploratory analysis identified two distinct subgroups: ‘increasing PPT’ and ‘decreasing PPT’. Subgroup membership was predicted using baseline CPM and EIH (p < 0.045).
This study found no significant changes in PPT, cPPT, or CPM following aerobic exercise. A significant change was observed in TSP. CPM and EIH predicted changes in PPT during the 15 km run (increasing vs. decreasing) in an explorative analysis. Further research should test if baseline tests can predict pro- or anti-nociceptive responses to long-distance running.
These findings highlight the importance of individual variability in endogenous pain modulation during endurance exercise. The lack of group-level effects underscores the need to move beyond average responses and consider subgroups when studying exercise-induced hypoalgesia. Identifying distinct modulatory profiles may offer insight into personalized exercise interventions and reveal stable traits related to pain regulation. This has potential clinical implications for tailoring exercise as a pain management strategy and for identifying individuals at risk of negative or absent hypoalgesic responses.
The perception and assessment of foetal pain remains a contentious topic due to challenges in evaluating and detecting non-verbal behaviours. While it is widely accepted that newborns experience pain, measured through validated behavioural scales, debate persists regarding the onset of pain perception during intrauterine development.
We reviewed the available literature to prepare a position paper, aiming to argue that foetuses in their 2nd to 3rd trimester may in fact feel pain and exhibit different shades of consciousness.
Emerging evidence challenges the binary view of consciousness (e.g., present/absent), suggesting that foetuses may possess some aspects of consciousness such as levels of awareness and responsiveness, both necessary and sufficient for pain perception. Advances in 4D ultrasound technology have enabled the assessment of foetal facial expressions indicative of pain, leading to the development of specialised foetal pain behaviour scales. Targeted hand movements, MEG and EEG provide further evidence of goal-directedness and action planning, while engagement in different learning paradigms (ex. habituation) provides evidence for preliminary memory and higher-order cognition.
Research into foetal pain will contribute not only to better clinical care but will enrich the fields of bioethics and neurodevelopmental neuroscience.
This position paper provides an overview of the current research concerning foetal pain behaviour and awareness. Reflections on foetal pain may bring insights not only to the pain field, but also to neuroethics, clinical and neurodevelopmental sciences.
Topical high-dose capsaicin treatment is a recommended therapy for localised neuropathic pain with good tolerability and no identified drug interactions. However, it is not effective for every patient. So far, few parameters in patient history have been identified as predictors for response to capsaicin treatment. The aim of this prospective non-interventional exploratory study was to improve prediction of treatment response to high-dose capsaicin by including quantifiable parameters and standardised questionnaires.
Forty-eight patients with peripheral neuropathic pain were included in the study. In addition to questionnaires assessing pain and patient-reported outcome measures, the function of transient receptor potential vanilloid 1 (TRPV1) receptors in the affected skin was assessed via functional laser-speckle-contrast-analysis (fLASCA) and sensory testing was performed. Furthermore, the effects of genetic variants in TRPV1 and endothelial NO-synthase (eNOS) were tested by genotyping for TRPV1 rs8065080 (c.1911A>G, p.I585V), TRPV1 rs222747 (c.1103C>G, p.M315I) and eNOS rs1799983 (c.894 T>G, p.D298E).
Patient-reported catastrophizing was identified as the most important response predictor. Higher vibration detection threshold and higher pressure pain threshold showed the highest prediction values of sensory parameters. Combined, these three parameters predicted over a quarter of the level of pain relief. The genetic variant for TRPV1 rs222747 showed a significant impact on pain relief with a pain relief prediction of 13% or more.
A higher pressure pain threshold, a higher vibration detection threshold, higher pain catastrophizing and the presence of the TRPV1 variant rs222747 are associated with more pain relief from high-dose capsaicin treatment and provide promising targets for future investigation.
This exploratory study identifies promising predictors for analgesic response to high-concentration capsaicin. The models generated in this study include a spectrum of different variables considering psychological factors as well as functional nerve-fibre assessments and genetic polymorphisms.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：