Pain Response Research Articles

Therapeutic Effects of Cortex Phellodendri, Epimedium brevicornu, and Earthworm on Chronic Prostatitis/Chronic Pelvic Pain Syndrome Mice

Background: The use of traditional Chinese medicine (TCM) for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is widespread. The purpose of this study is to investigate the preliminary mechanism of Epimedium brevicornu Maxim., Cortex Phellodendri Chinesis (CPC), and Earthworm in the CP/CPPS model. Methods: Fifty C57BL/6 male mice were randomized into five groups: control, model, Epimedium brevicornu Maxim, Earthworm, and Cortex Phellodendri chinensis (CPC). To induce experimental autoimmune prostatitis (EAP), T2 peptide immune emulsion was subcutaneously injected into all groups except the control group on days 0 and 14 to induce experimental autoimmune prostatitis. Except for the control and model groups, all other groups were treated with Epimedium brevicornu Maxim., CPC, and earthworm after the successful induction of EAP. Results: On days 1, 28, and 56, the micturition habits and pain sensitivity of rodents in each group were evaluated. Hematoxylin-eosin (H&E) staining was used to examine prostate inflammation, whereas enzyme-linked immunosorbent assay (ELISA) was used to measure the serum level of tumor necrosis factor-α (TNF). The Epimedium brevicornu Maxim. group significantly reduced the number of urine spots and frequency of pain response compared to the model group. Epimedium brevicornu Maxim. group and CPC group significantly reduced inflammatory cell infiltration and inflammatory lesions more than Earthworm groups. The serum levels of TNF-α were substantially reduced in the Epimedium brevicornu Maxim. and CPC groups compared to the model group. Conclusion: Our findings showed that Epimedium brevicornu Maxim outperformed CPC and Earthworm for EAP treatment, which relieves urinary tract symptoms, enhances pain threshold, and lowers inflammation.

Artificial mechano-nociceptive system based on transparent ITO/AlN/ITO memristor nociceptor neuron

Artificial nociceptors demonstrate significant potential in emerging fields such as intelligent prosthetics, humanoid robotics, and electronic skin, capable of transducing external noxious stimuli to the central nervous system. Unlike common sensory neurons, nociceptors exhibit unique characteristics, including “no adaptation,” “relaxation,” “threshold firing,” and “sensitization of allodynia/hyperalgesia.” This study presents a forming-free volatile transparent ITO/AlN/ITO memristor that emulates biological nociceptor behaviors. Leveraging this artificial nociceptor, an artificial mechano-nociceptive system is developed by integrating the ITO/AlN/ITO memristor into a piezoelectric force sensor system for pain sensing and noxious stimuli warning. This research contributes to the advancement of human cognitive capability emulation and artificial intelligence systems, particularly in the domain of pain perception and response.

Altered parasympathetic outflow and central sensitization response to continuous pain in cyclic vomiting syndrome: a functional magnetic resonance imaging study.

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to integrate peripheral autonomic outflow metrics, temporal summation of pain, and brain fMRI. BOLD fMRI and ECG were acquired from CVS patients and healthy adults during a rest condition and a sustained cuff pressure pain stimulus at the leg. After the latter scan, participants rated pain for the full 6-minute pain stimulus as well as first, middle, and last two-minutes to calculate temporal summation. During sustained pain, patients (n=13) exhibited greater reduction in heart rate variability within the high-frequency range (HF-HRV) and reduced anticorrelation between HF-HRV and fMRI signal in the anterior insula, pregenual anterior cingulate cortex, and ventrolateral and dorsolateral prefrontal cortex relative to healthy adults (n=13). Compared to healthy adults (n=14), patients (n=14) exhibited increasing pain intensity over the course of sustained cuff pressure. Seed-based functional connectivity analysis revealed for healthy adults (n=13), pain sensitization correlated with pain-induced increases in connectivity between primary somatosensory cortex and regions of interest in both left anterior insula/posterior orbitofrontal cortex and right pre-supplementary motor area, while this correlation was disrupted in CVS (n=10). Our results support altered central coding of nociceptive stimuli and autonomic responsivity of CVS patients in key brain regions implicated in autonomic control and interoception.

Naringenin Suppresses the Hyperexcitability of Trigeminal Nociceptive Neurons Associated with Inflammatory Hyperalgesia: Replacement of NSAIDs with Phytochemicals

The present study examines whether the systemic application of naringenin (NRG) reduces inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc) related to hyperalgesia, and compares its impact with that of diclofenac (DIC). To provoke inflammation, the whisker pads of rats were injected with complete Freund’s adjuvant, and subsequently, mechanical stimuli were administered to the orofacial region to determine the escape threshold. Compared to naïve rats, the inflamed rats showed a significantly lower mechanical threshold, and this reduced threshold returned to normal levels two days post-administration of NRG, DIC, and half-dose DIC plus half-dose NRG (1/2 DIC + 1/2 NRG). Using extracellular single-unit recordings, the activity of SpVc wide-dynamic range neurons was measured in response to mechanical stimulation of the orofacial area under anesthesia. The average firing rate of SpVc neurons when exposed to both non-painful and painful mechanical stimuli was significantly reduced in inflamed rats following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The heightened average spontaneous activity of SpVc neurons in rats with inflammation was significantly reduced following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The increased average receptive field size observed in inflamed rats reverted to normal levels after either NRG, DIC, or 1/2 DIC + 1/2 NRG treatment. These findings indicate that NRG administration can reduce inflammatory hyperalgesia linked to the heightened excitability of SpVc wide-dynamic range neurons.

New Pharmacological Insight into Etanercept and Pregabalin in Allodynia and Nociception: Behavioral Studies in a Murine Neuropathic Pain Model

Background/Objectives: Neuropathic pain is challenging to treat, often resistant to current therapies, and associated with significant side effects. Pregabalin, an anticonvulsant that modulates calcium channels, is effective but can impair mental and motor functions, especially in older patients. To improve patient outcomes, reducing the doses of pregabalin and combining it with other drugs targeting different neuropathic pain mechanisms may be beneficial. TNF-α blockers such as etanercept have shown potential in addressing neuropathic pain by affecting sodium channels, synaptic transmission, and neuroinflammation. This study evaluates the efficacy and safety of combining low doses of etanercept and pregabalin in allodynia and nociceptive tests. Materials and Methods: Male C57/BL6 mice underwent chronic constriction injury (CCI) of the sciatic nerve to induce neuropathic pain. They were divided into seven groups: sham control, CCI control, low and high doses of pregabalin, low and high doses of etanercept, and a combination of low doses of both drugs. Behavioral tests, including von Frey, hot-plate, and rotarod tests, were used to assess pain responses and motor activity. Results: The results indicated that a high dose of pregabalin significantly reduced mechanical allodynia and thermal hyperalgesia but impaired motor function. Conversely, low doses of etanercept alone had no significant effect. However, the combination of low doses of etanercept (20 mg/kg) and pregabalin (5 mg/kg) effectively alleviated pain without compromising locomotor activity. Conclusions: These results suggest a novel therapeutic strategy for neuropathic pain, enhancing analgesic efficacy while minimizing adverse effects.

Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain: A Systematic Review and Network Meta-Analysis.

Chronic back and lower extremity pain is one of the leading causes of disability worldwide. Spinal cord stimulation (SCS) aims to improve symptoms and quality of life. To evaluate the efficacy of SCS therapies compared with conventional medical management (CMM). MEDLINE, Embase, and Cochrane Library were systematically searched from inception to September 2, 2022. Selected studies were randomized clinical trials comparing SCS therapies with sham (placebo) and/or CMM or standard treatments for adults with chronic back or leg pain who had not previously used SCS. Evidence synthesis estimated odds ratios (ORs) and mean differences (MDs) and their associated credible intervals (CrI) through bayesian network meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for network meta-analyses was followed. The primary outcomes were pain-related end points, including pain intensity (measured by visual analog scale) and proportion of patients achieving at least 50% pain relief (responder rate) in the back or leg. Quality of life (measured by EQ-5D index score) and functional disability (measured by the Oswestry Disability Index score) were also considered. A total of 13 studies of 1561 patients were included in the network meta-analysis comparing conventional and novel SCS therapies with CMM across the 6 outcomes of interest at the 6-month follow-up. Both conventional and novel SCS therapies were associated with superior efficacy compared with CMM in responder rates in back (conventional SCS: OR, 3.00; 95% CrI, 1.49 to 6.72; novel SCS: OR, 8.76; 95% CrI, 3.84 to 22.31), pain intensity in back (conventional SCS: MD, -1.17; 95% CrI, -1.64 to -0.70; novel SCS: MD, -2.34; 95% CrI, -2.96 to -1.73), pain intensity in leg (conventional SCS: MD, -2.89; 95% CrI, -4.03 to -1.81; novel SCS: MD, -4.01; 95% CrI, -5.31 to -2.75), and EQ-5D index score (conventional SCS: MD, 0.15; 95% CrI, 0.09 to 0.21; novel SCS: MD, 0.17; 95% CrI, 0.13 to 0.21). For functional disability, conventional SCS was superior to CMM (MD, -7.10; 95% CrI, -10.91 to -3.36). No statistically significant differences were observed for other comparisons. This systematic review and network meta-analysis found that SCS therapies for treatment of chronic pain in back and/or lower extremities were associated with greater improvements in pain compared with CMM. These findings highlight the potential of SCS therapies as an effective and valuable option in chronic pain management.

Effect of experimental knee pain location on gait kinematics.

In this study, we investigated whether experimental knee pain alters lower limb kinematics and knee arthrokinematics during gait, and if this motor adaptation depends on the spatial characteristics of the painful stimulus. Twenty-one participants walked on a treadmill for 60-s trials, either without stimulation or while experiencing painful electrical stimulation in the medial, lateral or anterior region of the knee. Perceived pain location was analyzed using pain drawing. Gait spatiotemporal parameters, lower limb kinematics, and dispersion of the knee helical axes on the sagittal plane were quantified for each trial and compared between conditions using ANOVAs with repeated measures or Friedman tests. Pain perception was localized in the area the stimulation was applied to. Compared to walking without pain, participants demonstrated reduced knee extension (1.5 ± 1.5 degrees, p = 0.002) and reduced hip extension (0.8 ± 1.1 degrees, p = 0.037) when pain was induced in the anterior region, but not medially or laterally. Anterior knee pain increased the mean distance of the helical axes during late stance (0.7 [0.3, 1.4], p = 0.010), while medial pain increased both mean distance (0.3 [0.1, 0.5], p = 0.037) and mean angle (1.2 ± 1.4, p = 0.010) during early swing. Acute, experimental knee pain alters gait kinematics and increases the dispersion of the helical axis. These adaptations depend on the spatial characteristics of the painful stimulus. These adaptations may reflect an attempt of the central nervous system to protect the painful tissue while searching for a less painful movement strategy.

A Systematic Review and Meta-Analysis of Conditioned Pain Modulation in Children and Young People with Chronic Pain

Background/Objectives: Conditioned pain modulation (CPM) is a psychophysical experimental measure of the endogenous pain inhibitory pathway in humans, wherein one pain stimulus (the conditioning stimulus) is used to inhibit an individual’s perception of a second painful (test) stimulus. Research provides evidence of impaired endogenous inhibitory pain responses in adults with chronic pain. CPM is now increasingly applied in paediatric research and clinical practice. The primary aim of this systematic review was to examine the efficacy of CPM in paediatric chronic pain populations (6–24-year-olds) compared to pain-free children and young people (CYP). Methods: The protocol was registered on PROSPERO (CRD42020221927). A systematic search of seven databases was conducted from database inception to 20th June 2024. Study inclusion criteria were as follows: (i) recruited a sample of CYP aged 6 to 24 (inclusive) with chronic pain or who were pain-free; and (ii) applied a CPM paradigm comprising both a painful test and conditioning stimuli that were sufficiently detailed to allow for replication,(iii) adhered to a study design of randomised control trial, case control or cohort study, including cross-sectional or longitudinal; (iv) available in the English language. Study exclusion criteria were: (i) The CPM paradigm used a non-painful test or conditioning stimulus only; and (ii) was only available as an abstract, letter, poster, editorial, case report, or review with or without meta-analyses. Risk of bias was assessed using the Appraisal Tool for Cross Sectional Studies (AXIS). Meta-analyses were conducted in Comprehensive Meta Analysis 3.0 using random effects models to compare the overall CPM responses in CYP with chronic pain conditions to healthy control CYP. Results: Thirty-two studies were eligible for inclusion, six of which were included in one or more meta-analysis (n = 407 chronic pain, n = 205 control). Meta-analysis revealed significantly weaker CPM responses in CYP with a variety of chronic pain conditions compared to healthy controls (standardized mean difference (SMD) = 0.352), and significantly weaker CPM responses in CYP with abdominal pain conditions compared to healthy controls (SMD = 0.685). No significant difference in CPM response was found between CYP with migraine and healthy controls (SMD = −0.201). Conclusions: Variable results were found across individual studies, and the meta-analysis of the small number of eligible studies provides tentative evidence for impaired CPM in CYP with chronic pain compared to healthy controls. Further research is clearly needed. In particular, studies should present CPM results separately for different age groups, ethnic groups, and sexes, as these variables shape clinical pain responses.

A case series and review of stereotactic body radiation therapy for contiguous multilevel spine metastases.

A majority of published series report on stereotactic body radiation therapy (SBRT) for 1-2 contiguous vertebral levels due to concerns regarding setup accuracy and radiation toxicity. This study evaluates patients with metastases spanning ≥ 3 contiguous levels treated with SBRT and augments its findings with a review of other studies investigating multilevel spine SBRT. Analysis of a prospectively collected database of 49 patients with 55 metastases spanning ≥ 3 contiguous vertebral levels treated with SBRT at a single institution (2002-2023) was performed. Outcomes identified included local failure (LF), pain response, overall survival, and toxicity. The median single-fraction prescription dose was 15Gy (range: 8-18); multifractionated treatment utilized prescription doses of 18-30Gy in 2-5 fractions. Median follow-up was 7 months (range: 1-103). The 6-month, 1-year, and 2-year cumulative incidence rates of LF were 7%, 11%, and 11%, respectively. No prognostic factors were associated with LF. Pain was reported to improve or remain stable for 49 lesions (89%). Ten adverse radiation events (18%) were identified; pain flare (5%), dermatitis (4%), and vertebral compression fracture (VCF, 9%). The 3-month, 6-month, and 1-year cumulative incidence rates of VCF were 4%, 7%, and 7%, respectively. No instances of esophageal toxicity or myelopathy were observed. This study of multilevel SBRT is one of the largest to investigate outcomes in this challenging clinical scenario. Spine SBRT confers low rates of LF and toxicity for patients with multilevel disease, which was previously considered a relative contraindication. Spine SBRT may be considered in this patient population instead of low-dose palliative RT.

An Alternative Approach for Evaluating Induced and Contact Currents for Compliance with Their Exposure Limits (100 kHz to 110 MHz) in IEEE Std C95.1-2019.

The Institute of Electrical and Electronics Engineers establishes exposure reference levels (ERLs) for electric fields (E-fields) (0-300 GHz) and both induced (IIND) and contact currents (ISC) (<110 MHz) in its standard, IEEE Std C95.1™-2019 (IEEE C95.1). The "classical" scenarios addressed in IEEE C95.1 include a free-standing, grounded "reference" person (IIND) or an ungrounded reference person in manual contact with an adjacent grounded conductor (ISC), each exposed to a vertically oriented E-field driving the currents. The ERLs for current from 100 kHz to 110 MHz were established to limit heating in the finger (from touch), ankle (IIND), and wrist (ISC from grasp contact), specifying the 6-min average specific absorption rate (SAR, W kg-1) as the dosimetric reference limit (DRL); whole-body E-field ERLs are 30-min averages. The DRLs were established assuming a default "effective" local cross-section (9.5 cm2) and consistent with a composite tissue conductivity of ~0.5 S m-1. A previous publication described the misalignment of the ERLs for E-fields with the ERLs for IIND (which extends to ISC) and also proposed a ramped E-field ERL from 100 kHz to 30 MHz. For the frequency range 100 kHz to 110 MHz, this paper proposes temperature increase (ΔT) in ankle and wrist as the preferred effect metric associated with IIND and ISC; applying the E-field ERLs as surrogates for limits to these currents; and adopting the proposed ramp. The analysis of ΔT is based on the tissue mix in realistic anatomic depictions of ankle and wrist cross-sections; relevant tissue properties posted online; published tissue perfusion data; and anthropometric data on a large sample of male and female adults in the US military, allowing an estimate of effects over a range of body size. To evaluate ΔT versus frequency and time, the Penne bioheat equation was adapted with convective cooling from arterial blood as the lone cooling mechanism. The analysis revealed that IINDs and ISCs induced by ERL-level E-fields produce SARs in excess of the local DRLs (in some cases far exceed). Calculations of time to ΔT of 5 °C, reflective of a potentially adverse (painful) response, resulted in worst-case times for effects in the ankle on the order of minutes but on the order of 10s of s in wrist. Thus, compliance with the E-field ERL, as assessed as a 30-min whole-body average is incompatible with the time course of potentially adverse effects in ankle and wrist from IIND and ISC, respectively. Further analysis of the relevant exposure/dose scenarios and consensus of stakeholders with a multi-disciplinary perspective will enable the development of a revised standard, practical from a compliance perspective and protective of all persons.

The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review’s specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community.

The impact of fear of pain on the temporal processing of emotional faces: modulation of attentional resources.

Recent research has focused on the spatial attention bias toward pain-related cues in individuals with fear of pain (FOP), but our understanding of its temporal attention features, particularly regarding emotional faces, is limited. To address this gap, 39 individuals with high fear of pain (H-FOP) and 37 with low fear of pain (L-FOP) completed a rapid serial visual presentation dual task. Participants viewed a series of rapidly presented pictures, first identified neutral building images as the first target (T1) and then emotional faces (painful, neutral, and happy) as the second target (T2). T1 and T2 presented at time intervals of 232ms (lag 2) and 696ms (lag 6), respectively. Results indicate that H-FOP group members were less accurate in recognizing faces at lag 2 shortly after correctly identifying T1 compared to those L-FOP group members. Notably, all participants were more accurate in recognizing painful faces at lag 2 than in identifying neutral and happy faces, suggesting a negative bias toward pain stimuli when attentional resources were limited. In contrast, at lag 6, when attentional resources were more abundant, participants showed greater accuracy in recognizing neutral faces than emotional faces. These findings underscore the influence of fear of pain and available cognitive resources on the attentional processing of emotional faces over time, providing insights into how fear of pain affects the temporal dynamics of emotional face recognition and the role of attentional resources.

Impact of Structural Severity on Outcomes in Knee Osteoarthritis: An Analysis of Data from Phase 2 and Phase 3 Lorecivivint Clinical Trials.

Developing knee osteoarthritis (OA) treatments is challenging due to assessing pain and joint structure outcomes within a highly heterogeneous disease. Lorecivivint (LOR), an intra-articular (IA) CLK/DYRK inhibitor, modulates Wnt and inflammatory pathways. This review analysis of LOR 0.07 mg trial data aims to describe the potential impact of baseline joint structure on OA pain response. Two Phase 2 and two Phase 3 trials enrolled knee OA patients with Kellgren-Lawrence (KL) Grades 2-3 and Pain Numeric Rating Scale (NRS [0-10]) ≥4 to ≤ 8 in target knee. Cumulative frequency distribution plots by KL grade summarized the percentages of patients with medial joint space width (medial JSW) < 3 mm. Osteoarthritis Research Society International Joint Space Narrowing grades and treatment responses in trials capturing Pain NRS were similarly summarized. Pain outcome changes were estimated using baseline adjusted ANCOVA. Compared with phase 2 trials, the phase 3 trials had an increased proportion of patients with baseline medial JSW < 3 mm. LOR demonstrated beneficial treatment effects vs placebo in KL 2 subgroups, which were found to have higher proportions of baseline medial JSW > 3 mm, apart from one Phase 3 trial with advanced structural knee OA. Baseline medial JSWs were heterogeneous across trials despite KL inclusion criteria. LOR demonstrated greater symptomatic improvements in patients with less structurally advanced disease, indicative of an association between OA structural damage and pain. Early treatment interventions may improve outcomes and provide insight for future OA trial inclusion criteria development. OA-02, NCT02536833; OA-04, NCT03122860; OA-10, NCT04385303; OA-11, NCT03928184.

Neural empathy mechanisms are shared for physical and social pain, and increase from adolescence to older adulthood.

Empathy is a critical component of social interaction that enables individuals to understand and share the emotions of others. We report a pre-registered experiment in which 240 participants, including adolescents, young adults and older adults, viewed images depicting hands and feet in physically or socially painful situations (vs. non-painful). Empathy was measured using imagined pain ratings and EEG mu suppression. Imagined pain was greater for physical vs. social pain, with young adults showing particular sensitivity to social pain events compared to adolescents and older adults. Mu desynchronisation was greater to pain vs. no-pain situations, but the physical/social context did not modulate pain responses. Brain responses to painful situations increased linearly from adolescence to young and older adulthood. These findings highlight shared activity across the core empathy network for both physical and social pain contexts, and an empathic response that develops over the lifespan with accumulating social experience.

Pain-Discriminating Information Decoded From Spatiotemporal Patterns of Hemodynamic Responses Measured by fMRI in the Human Brain.

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses.

Physiological Time-Series Fusion With Hybrid Attention for Adaptive Recognition of Pain.

Automatic pain assessment is an application in healthcare serving personalized pain care, and patients cannot self-report pain. Pain at the present is inferred from physiological dynamics at the present and in the near past. However, heterogeneous pain responses cross-subject and cross-type hinder accurate recognition of pain. This work solves the adaptive pain recognition problem across pain types. We concrete the adaptivity problem into recognizing both phasic/short and tonic/long pain from the physiological sequences of the same length. The adaptivity of the proposed solution (TCAtt-PainNet) was ensured by hybrid temporal-channel attention when fusing multivariate time-series of electrocardiogram (ECG) and galvanic skin response (GSR) features. The attention was obtained by learning the dependencies between the point at present and the sequence in the near past, where sequence point temporal attention was constructed via modified self-attention, and the following feature channel attention was constructed by squeeze-and-excitation temporal attention weighted deep feature sequence. The proposed solution successfully enhanced recognition adaptivity by addressing relevant information only from long input sequences when testing with tonic and phasic pain databases, making progress towards automatic pain assessment for real application scenarios with attributes unknown pain.

Unraveling the therapeutic potential of Astilbe rivularis Buch.-Ham. ex D. Don in attenuation of diabetic neuropathy in laboratory rats

Ethnopharmacological relevanceAstilbe rivularis Buch.-Ham. ex D. Don is a rare medicinal plant, traditionally employed for treating several disorders. The juice, decoction or powder of the roots, rhizomes, leaves and even the entire plant, are used for managing peptic ulcer, diarrhoea, jaundice, sprains and muscular swellings, bone fracture and dislocation of joints, postpartum bleeding and other menstrual disorders. These conventional medicinal uses make Astilbe rivularis a promising candidate for further research. Aim of the studyThis study was designed to explore the neuroprotective potential of hydroethanolic extract of Astilbe rivularis (ARHE) in diabetic neuropathy (DN) in rats. Materials and methodsGC-MS analysis was used to identify the phytoconstituents present in the plant extract. DN was induced by administration of STZ (55 mg/kg, i.p.), 15 min after NAD (230 mg/kg, i.p.) injection. The rats with fasting blood glucose (FBG) level >250 mg/dl were included in the study. DN was assessed by estimating the level of FBG, lipid profile, and invitro and invivo oxidative stress parameters. Additionally, behavioural parameters like, mechanical hyperalgesia, hot and cold allodynia were estimated to assess diabetic neuropathy. Furthermore, the level of antioxidant enzymes like SOD, GSH, and TBARS in sciatic nerve and inflammatory markers like, TGF-β and IL-6 were measured. ResultsAltogether, 30 phytoconstituents were identified including heptafluorobutyric acid, hexadecanoic acid, and beta-sitosterol depicting antioxidant, antidiabetic, and anticancer properties, respectively. Administration of different doses (100, 200, and 400 mg/kg) of ARHE to diabetic rats attenuated elevated blood glucose level and restored lipid profile, body weight, food and water intake, and antioxidant level. Moreover, elevated level of inflammatory markers like, TGF-β and IL-6 was also found to be attenuated in sciatic nerve. Furthermore, ARHE attenuated the pain response assessed by mechanical hyperalgesia and hot and cold allodynia in diabetic neuropathy rats. ARHE also showed inhibitory activity on ALR enzyme and erythrocyte sorbitol accumulation, and ameliorated oxidative stress. Histopathological study indicated improvement in the architecture of sciatic nerve tissue in diabetic neuropathy rats with the treatment of ARHE. ConclusionsConclusively, hydroethanolic extract of Astilbe rivularis exhibited neuroprotective potential and ameliorated diabetic neuropathy in rats.

USO DA TERAPIA FOTODINÂMICA E DA CRIOTERAPIA NO CONTROLE DA DOR APÓS O TRATAMENTO ENDODÔNTICO: RELATO DE CASO CLÍNICO

Patients may undergo endodontic treatment for many reasons, including the presence of extensive decay that exposes pulp tissue and tooth fractures. The treatment, in turn, can generate, in some cases, the presence of painful symptoms, due to numerous reasons, such as incorrect removal of the smear layer and chemical injuries from the irrigating material. To reduce patient discomfort, alternative technical applications can be used to control post-operative pain, such as cryotherapy and laser therapy. The objective of this work, in the form of a case report, was to show the importance of controlling postoperative pain after endodontic treatment using laser therapy and cryotherapy techniques. Searches were carried out in electronic databases: Virtual Health Library (VHL), Scientifc Electronic Library Online (Scielo) and PubMed for the last 7 years (2017 to 2024), in addition to patient care where cryotherapy was used using serum physiological cold and laser therapy was performed. The results presented were satisfactory, as after 4 sessions, pain was assessed through telephone contact with the patient over periods of 24h, 72h and 7 days, where the patient’s pain-free response was verified and without need of analgesic use. The present study can conclude that performing cryotherapy concomitantly with the use of laser therapy presents a significant reduction in the postoperative pain response.

ANALYSIS OF KNOWLEDGE AND ATTITUDES REGARDING PAIN MANAGEMENT IN NURSES WORKING IN NEONATAL UNIT

Effective neonatal pain management is crucial in Neonatal Intensive Care Units (NICUs), yet gaps in knowledge and attitudes among nursing staff can impact the quality of care. Understanding these gaps is essential to developing strategies for improved training and patient care outcomes. Objective: To assess the knowledge and attitudes regarding management in nurses working in neonatal ICU. Methods: The cross-sectional study was conducted in the Neonatal Intensive Care Unit Hospital from September 2023 to August 2024. A total of 100 neonatal nurses working in the NICU for at least a year were included in the study. Data was collected through a 42-item questionnaire divided into three sections. The first part included 10 questions about nurses’ demographics. The second part included 21 questions to inquire about knowledge of neonatal pain management which could be answered on a Likert scale from 1 to 5 with being strongly disagree and 5 being neutral. The last sections included 11 questions to assess nurses’ attitudes regarding the subject which could be responded to on a Likert scale. Results: Nurses had a poor knowledge level regarding neonatal pain management. 92% of nurses were capable of identifying a neonate in pain, however, 30% wrongly agreed that neonatal pain response was less than adults. 32% of nurses were of the perspective that parents should not be present during invasive procedures. 50% of nurses wrongly thought of sedation as the best pain relief. More than 80% of nurses were positive about palliative care for chronically ill neonates. However, 45% of nurses did not think that surgeries and invasive procedures should ease neonatal pain. Conclusion: Poor knowledge and moderately satisfactory attitude were noted in neonatal nurses regarding neonatal pain management. Improvement in awareness programs and training is urgently needed to improve patient care.

Influence of instructions and expectations in pain perception on pupil diameter and the cognitive assessment of pain

ObjectiveThe purpose of this study was to analyze the influence of pain and no pain expectation on pupil diameter and the cognitive assessment of pain using pupillometry and the visual analog scale (VAS). MethodsThis was an experimental cross-sectional study in which painful stimulation of the muscle masseter was produced by palpation with an algometer in a sample of 30 healthy participants. Before the painful stimulation, pain expectation and no pain expectation situations were induced by employing instructional videos. Cognitive and physiological pain responses were measured by the VAS and by pupillometry. Visual analog scale score was assessed at the end of each experimental condition, and pupillometry measurements were recorded at different moments of the experimental process (events). ResultsThe pain score and larger pupil diameter for all events (except, as expected, for the initial baseline), were statistically significant for the pain expectation condition compared with the no pain expectation. ConclusionWithin the conditions of this study, pain expectation modulated both cognitive assessment of pain (VAS) and pupil diameter. These findings suggest that pupil diameter may be a useful and complementary tool with the VAS for pain assessment. Furthermore, the findings support models postulating that emotion and cognition are important aspects involved in pain perception, which is in line with the recent International Association for the Study of Pain definition of pain.