Pain Response Research Articles

An Argument for Unconscious Mental Qualities

ABSTRACT Conscious mental qualities, aka phenomenal qualities, are seemingly a leading factor in much of our behaviour. Pains make us recoil from painful stimuli, itches make us scratch, feelings of anger sometimes make us shout, visually perceiving red leads us to halt at stop lights, and so on. To relinquish this claim about the efficacy of conscious mental qualities would mean surrendering a major component of our everyday, intuitive self-conception; hence, the claim enjoys considerable prima facie plausibility. Unconscious mental qualities, however, have been posited by a mere handful of philosophers historically, and are nowadays almost universally rejected. Via a case study of ‘restless legs syndrome’, I argue that there is a hitherto unnoticed cost to this prevailing rejection of unconscious mental qualities: the causal efficacy of conscious mental qualities is threatened. In fact, I argue, we face a dilemma: To endorse epiphenomenalism about conscious mental qualities, or to posit unconscious mental qualities. Since it is so plausible that conscious mental qualities are causally efficacious, this reasoning constitutes an argument for unconscious mental qualities. Moving beyond the sensory case, I explain how analogous reasoning might apply to other mental faculties where phenomenal qualities seem causally involved: notably, emotions and mental imagery.

C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models.

Antagonists (e.g., Ziconotide, Gabapentin) of the CaV2.2 (N-type) calcium channels are used clinically as analgesics for chronic pain. However, their use is limited by narrow therapeutic windows, difficult dosing routes (Ziconotide), misuse and overdoses (Gabapentin), as well as a litany of adverse effects. Expansion of novel pain therapeutics may emerge from mechanism-based interrogation of CaV2.2. Here we report the identification of C2230, an aryloxy-hydroxypropylamine, as a CaV2.2 blocker. C2230 trapped and stabilized inactivated CaV2.2 in a slow-recovering state and accelerated the open-state inactivation of the channel, conferring an advantageous use-dependent inhibition profile. C2230 inhibited CaV2.2 during high-frequency stimulation, while sparing other voltage-gated ion channels. C2230 inhibited CaV2.2 in dorsal root and trigeminal ganglia neurons from rats, marmosets, and humans in a G-protein-coupled receptor-independent manner. Further, C2230 reduced evoked excitatory postsynaptic currents and excitatory neurotransmitter release in the spinal cord, leading to relief of neuropathic, orofacial, and osteoarthritic pain-like behaviors via three different routes of administration. C2230 also decreased fiber photometry-based calcium responses in the parabrachial nucleus, mitigated aversive behavioral responses to mechanical stimuli after neuropathic injury, and preserved protective pain responses, all without affecting motor or cardiovascular function. Finally, site-directed mutation analysis demonstrated that C2230 binds differently than other known CaV2.2 blockers, making it a promising lead compound for analgesic development.

Obituary. Tipu Zahed Aziz, 1956-2024

The extraordinary life of Tipu Aziz is described through anecdotes told to his former residents and fellows. A giant of functional neurosurgery, his primate experiments first demonstrated the subthalamic nucleus and pedunculopontine nucleus as targets for surgery for Parkinson's disease and he pioneered deep brain stimulation for pain including of the anterior cingulate cortex. Despite various career cul-de-sacs he climbed the ziggurat to the pinnacles of British neurosurgery and neuroscience. A pinball wizard of functional neurosurgery, he was mentored by a bygone Madmen era of gentlemen: chain-smoking, heavy-drinking workaholics whose nonchalant bravado, ‘can-do’ attitude, love of mischief, merriment and well-placed profanity he exemplified. Sometimes sharing a cigarette with a patient before surgery, we will not see his like again.

Efficacy and tolerability of single-fraction radiotherapy for spinal bone metastases in a low-middle-income country setting: a prospective study

AimsThis study aimed to evaluate the symptomatic efficacy and tolerability of three different radiotherapy (RT) regimens for patients with vertebral metastases in a low-middle-income country setting, focusing specifically on the effectiveness of single-fraction radiotherapy.MethodsConducted at the National Institute of Cancer Research and Hospital, Bangladesh, from July 1, 2020, to June 30, 2021, this prospective, non-randomized study enrolled 90 patients aged 18 to 75 years with histologically confirmed primary malignancies and vertebral metastases. Patients were allocated to one of three treatment arms: 8 Gy in a single fraction (Arm A), 20 Gy in 5 fractions (Arm B), or 30 Gy in 10 fractions (Arm C). The primary endpoint was pain response at 12 weeks, assessed by the Visual Analogue Scale and International Bone Metastases Consensus. Secondary endpoints included toxicity, measured by the Common Terminology Criteria for Adverse Events, and overall survival.ResultsPain control at 12 weeks showed no significant differences among the treatment groups, with 70% of patients in Arm A, 67% in Arm B, and 70% in Arm C experiencing either partial or complete pain relief (p = 0.95). The overall survival rates were comparable across the groups (median survival, 7 months for arms A and C, 6 months for Arm B). Skin toxicity was significantly lower in Arm A (10% incidence) compared to arms B (30%) and C (47%) (p = 0.017). There were no reports of Grade 3 or higher toxicities.ConclusionThe study confirms the efficacy and safety of single-fraction RT for spinal bone metastases, providing significant pain relief and lower skin toxicity relative to multiple fraction regimens. These results confirm the efficacy of single-fraction RT in the treatment of vertebral metastases also in resource-limited settings, suggesting its broader adoption to reduce toxicity and treatment burdens in low-middle-income countries.

Electroencephalographic power ratio and peak frequency difference associate with central sensitization in chronic pain.

Central sensitization, or increased responsiveness of the central nervous system to sensory input, is present in many chronic pain patients. Clinically, it is detected through subjective, patient-reported measures. There is a need for reliable, direct measurements of neural response to controlled stimuli to quantify neuronal dysfunction in pain. The goal of this work is to investigate cortical activity, recorded via electroencephalogram (EEG), during objective and calibrated painful stimulation in chronic pain patients.&#xD;Approach. Chronic pain patients (N=8) and healthy controls (N=8) participated in this study. We recorded electroencephalography (EEG) at rest (baseline) and during evoked pain tasks, including thermal and mechanical stimuli. The evoked pain was applied following the quantitative sensory testing (QST) protocol, which is a research technique that applies objective, calibrated painful stimuli. &#xD;Main results. Peak alpha frequency at rest was significantly lower in chronic pain patients compared to healthy controls (p<0.0002), while EEG alpha/theta and alpha/beta power ratios at rest were higher in patients (p<0.0002). During thermal QST, these power ratios decreased in patients and increased in controls (p<0.0002 for both). During mechanical QST, power ratios decreased or did not change. Furthermore, the peak theta-beta frequency difference at baseline was significantly lower in patients compared to controls (p<0.0002). During thermal QST, this difference increased in patients and decreased in controls; during mechanical QST, this difference increased in both patients and controls (p<0.0002). Functional connectivity analysis showed that controls had greater baseline theta connectivity strength that increased during mechanical QST (p<0.0002).&#xD;Significance. This work demonstrates differential patterns of EEG activity at rest and during acute painful stimulation in chronic pain patients compared to healthy controls. These measures may quantify an individual's tendency to experience chronic pain and central sensitization and serve as diagnostic biomarkers.

Pain management with virtual reality in burn patients: a literature review.

Burns are injuries to the skin or the underlying tissue system caused by heat, radiation, electricity, friction or chemicals. Burns can cause pain and discomfort during dressing changes; a person's pain response varies depending on individual perception. The pain response can indicate tissue damage in the body, as pain causes a person to experience discomfort. Pain can be interpreted as a subjective sensory response and an unpleasant emotional experience associated with actual or potential tissue damage. Pain is usually managed with pharmacological and non-pharmacological therapy. An example of non-pharmacological therapy is the use of distraction techniques, such as virtual reality (VR). VR diverts pain by creating a 3D environment with a screen and VR glasses. It allows the patient to immerse themselves in a virtual world complete with sound and music. The volume can be adjusted as needed and the patient can interact with the virtual world. The purpose of this study is to determine the characteristics and effectiveness of VR pain management in burn patients. The method used in this study is a literature review using the Preferred Reporting Items For Systematic Review (PRISMA). The authors searched for journal articles using the Science Direct, PubMed, and Google Scholar databases, covering the period from 2015-2023. The keywords used were pain management, virtual reality and burn injury. Based on the predetermined inclusion criteria, 10 articles were selected for the review. The results of this study, based on the analysis of 10 articles, indicated that the distraction or transition method (non-pharmacological management using VR) was effective in reducing pain and discomfort during dressing changes in patients with mild to moderate burns, across various age groups from infants and children to adults. Clinicians can leverage VR technology to tailor interventions based on individual patient needs, across all age groups, enhancing patient comfort and engagement during procedures.

Adult Phenotype of CHD2-Associated Disorders.

Pathogenic CHD2 variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric CHD2 phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with CHD2 variants. Patients 18 years or older with likely pathogenic or pathogenic (LP/P) CHD2 variants were included. We used standardized tools to evaluate current seizures, medication use, sleep, gastrointestinal symptoms, pain response, gait, social communication disorder, and adaptive behavioral skills of patients. In this prospective study, 14 unrelated adult patients (age range: 18-45 years, median: 21 years) with LP/P CHD2 variants were described. Eleven novel variants were identified. No genotype-phenotype correlations were identified. 79% of adults still have ongoing seizures. Photosensitivity was present in 64% of adult patients. Autism spectrum disorder was diagnosed in 71% of patients. Only 29% were able to read and understand material at a sixth-grade level or higher. Behavioral issues were reported in 100% of adult patients, and 71% had internalizing features, such as anxiety. Self-injurious behaviors were present in 50%. Only 43% could ambulate independently. Additional characteristics included reflux (36%), constipation (71%), and abnormal pain responsiveness (43%). 1 patient presented with nonepileptic breath-holding spells leading to cyanosis. No patient could perform all basic activities of daily living independently, all the time. Higher seizure severity was associated with worse nonseizure outcomes (p = 0.04). Most adults with CHD2 continue to have seizures, and seizure severity is associated with worse comorbidities such as maladaptive behaviors, gait, gastrointestinal, sleep, and abnormal pain responsiveness. Longevity has not been systematically studied in this group of patients. Here we describe a group of adult patients (up to 45 years of age) and the natural history of this condition. These data may provide prognostic insights for families of pediatric patients and help identify key points to be addressed in future precision trials for patients with CHD2 variants.

Pain, oedema and trismus responses following photobiomodulation therapy immediately after lower third molar extraction: results of a randomised, doble-blind and split mouth clinical trial

Pain, oedema and trismus responses following photobiomodulation therapy immediately after lower third molar extraction: results of a randomised, doble-blind and split mouth clinical trial

Anti-nociceptive effects of non-antibiotic derivatives of demeclocycline and doxycycline against formalin-induced pain stimulation

In previous studies, some tetracycline (TC) antibiotics showed potential as analgesic. We investigated here the analgesic activity of new non-antibiotic TC derivatives using the formalin-induced nociceptive pain model in adult C57BL/6 mice. Specifically, we tested the effects of i.p. injections of DDMC (5, 10, 20 mg.kg-1) and DDOX (10, 20, 40 mg.kg-1), which are non-antibiotic derivatives of demeclocycline and doxycycline, respectively. Repeated treatments with DDMC remarkably reduced nociceptive pain in both phases of the test, at 10 mg.kg-1 its efficacy was comparable to that of 10 mg.kg-1 of morphine. DDOX was also effective in this paradigm but intrinsically less potent than DDMC, exerting analgesic effects between 20 and 40 mg.kg-1. Interestingly, a single injection of DDMC (10 mg.kg-1) was sufficient to produce a robust anti-nociceptive effect similar to that of morphine. A single injection of DDOX (40 mg.kg-1) also produced anti-nociceptive effects but only in the second phase of the test. Noticeably, male mice exhibited a better analgesic response to DDMC (10 mg.kg-1) than females. A single injection of DDMC (10 mg.kg-1) and morphine but not of DDOX (40mg.kg-1), powerfully inhibited formalin-induced spinal cord c-Fos expression whereas both TC derivatives restrained the activation of Iba-1-immunoreactive cells, indicating a potential indirect effect on inflamed microglial cells. In summary, the non-antibiotic TCs, DDMC and DDOX, demonstrated notable analgesic efficacy against formalin-induced pain, suggesting their potential as alternatives for analgesic treatment.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study.

Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes. In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy. IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (p<0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all p<0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: p=0.002 and p=0.003; pressure: both p<0.001) and WUR (both p<0.001). FMS participants exhibited reduced corneal nerve fibre density (p=0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all p<0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23). Participants with SFP,in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.

Molecular Chaperones to Pain Modulators: Heat Shock Proteins the Emerging Players in Chronic Pain Management.

Chronic pain is the most prevailing complex syndrome among clinical disorders affecting approximately 30% of people globally. Various intricate alterations in nociceptive pathways responsible for chronic pain are linked to long-term tissue damage or injury to the peripheral or central nervous systems. These include remolding in the phenotype of cells and fluctuations in the expression of proteins such as ion channels, neurotransmitters, and receptors. Heat shock proteins are important molecular chaperone proteins in cell responses to stress, including inflammation, neurodegeneration, and pain signaling. They play a key role in activating glial and endothelial cells and in the production of inflammatory mediators and excitatory amino acids in both peripheral and central nervous systems. In particular, they contribute to central sensitization and hyperactivation within the dorsal horn of the spinal cord. The expression of some HSPs plays a remarkable role in upregulating pain response by acting as scavengers of ROS, controlling inflammatory cytokines. Different HSPs act by different mechanisms and several important pathways have been implicated in targeting HSPs for the treatment of neuropathic pain including p38-mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases (ERKs), brain-derived neurotrophic factors (BDNF). We summarize the role of HSPs in various preclinical and clinical studies and the crosstalk of HSPs with various nociceptors and other pain models. We also highlighted some artificial intelligence tools and machine learning-assisted drug discovery methods for rapid screening of HSPs in various diseases. Thus, targeting HSPs may provide new therapeutic opportunities for the management of chronic pain conditions and expand our understanding of pain in neurological disorders and other pathological conditions.

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&amp;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.

Tympanic membrane repair using improved endoscopic ear canal flap dissection method

Objective:To investigate the clinical value of tympanic membrane repairment with modified ear canal flap under endoscope. Methods:A retrospective analysis was conducted on the clinical data of 62 patients who underwent simple tympanic membrane perforation repair surgery in our hospital from August 2019 to January 2023. All patients were divided into two groups: 37 cases in the otoscopy group and 25 cases in the microscope group. The surgical duration, postoperative pain response, and postoperative tympanic membrane healing and hearing recovery were compared between the two groups. Results:Compared with the microscope group, the total surgical duration of the otoscopy group was significantly shortened[（70.4±13.2） min vs. （102.8±17.5） min, P<0.001], and there was a statistically significant difference in postoperative VAS pain score[（3.1±1.2） vs. （6.5±1.4）, P<0.001]. The two groups achieved tympanic membrane healing and no infection occurred after operation. There was no significant difference in postoperative hearing recovery between the two groups（P>0.05）. Conclusion:Modified tympanic membrane repairment through otoscope can greatly shorten the operation time and reduce the hospitalization cost, which is more suitable for the application of primary hospitals.

Gamma Knife radiosurgery for relapsing trigeminal neuralgia following microvascular decompression.

Gamma Knife radiosurgery (GKRS) is a treatment option for refractory trigeminal neuralgia (TN). However, there is a paucity of data regarding the effectiveness of GKRS for relapsing TN following microvascular decompression (MVD). The aim of this study was to characterize the response rate, complications, pain relief durability, and predictors of pain relapse for salvage GKRS following MVD for TN. A retrospective study of all patients who received GKRS for Burchiel type 1 TN (TN1) or type 2 TN (TN2) pain at Wake Forest University School of Medicine was conducted. Pain was measured using the Barrow Neurological Institute (BNI) pain intensity score. After an initial pain response of BNI scores I-III, a BNI score of IV or V constituted relapse. Durability of pain relief was characterized using the Kaplan-Meier estimator. Predictors of relapse were investigated using Cox regression models. Statistical significance was set at p < 0.05. Of 2065 patients with TN1 or TN2, 59 had GKRS post-MVD. Forty-nine (83.1%) of these patients experienced a BNI pain score of I-III at the first follow-up post-GKRS. The median time to relapse was 1.75 years; freedom rates from relapse were 77%, 45.9%, and 30.7% at 1, 2, and 5 years, respectively. Radiofrequency ablation prior to MVD significantly decreased the likelihood of an initial response to salvage GKRS (Fisher's exact test, p = 0.02). After controlling for baseline and clinical characteristics, facial numbness significantly decreased the likelihood of pain relapse (Cox regression, HR 0.15, 95% CI 0.03-0.73; p = 0.01). Conversely, a worse initial pain response significantly increased the likelihood of pain relapse (Cox regression, HR 3.64, 95% CI 1.02-12.95; p = 0.04). Pain relapse within 24 months of the original MVD did not predict durability of pain relief following salvage GKRS (Cox regression, HR 0.94, 95% CI 0.40-2.22; p = 0.89). The overall toxicity rate of salvage GKRS was 35.6%. Salvage GKRS presents an effective, noninvasive option for recurring TN after MVD, with a comparable response rate to primary GKRS or MVD, and a favorable complications profile relative to salvage MVD. Patients with postoperative facial numbness and a better initial pain response may experience more durable pain relief following salvage GKRS.

Effect of cyclo-L-prolylglycine on pain response thresholds and morphine-induced analgesia in inbred BALB/c and C57Bl/6 mice

Effect of cyclo-L-prolylglycine on pain response thresholds and morphine-induced analgesia in inbred BALB/c and C57Bl/6 mice

High-Fatigue Dynamic Resistance Exercise Induces Significant Hypoalgesia Effect.

Hogge, R, Mascheri, M, Shurik, D, Hanney, WJ, and Anderson, AW. High-fatigue dynamic resistance exercise induces significant hypoalgesia effect. J Strength Cond Res XX(X): 000-000, 2024-Although dynamic resistance exercise is a recommended treatment for patients with musculoskeletal pain, optimal intensity to create hypoalgesia has not been established. Response to exercise may also be affected by biopsychosocial factors that modulate pain response. The first purpose was to compare the immediate effects of a high-fatigue/exertion leg extension, low-fatigue/exertion leg extension, and control condition on pressure pain threshold (PPT) applied to the quadriceps (local effects) and trapezius (systemic effects). The second purpose was to examine if psychological and pain sensitivity factors affected response to exercise. As a within-subject design, subjects completed psychological questionnaires, a control condition, and a 1-repetition maximum (1RM) during the first session. Subjects attended 2 more sessions where they completed 3 sets of a leg extension exercise at 50% of their 1RM until they reached a fatigue level of high fatigue (8/10 on the Borg CR-10) or low fatigue (3/10) with a randomized session order. A within-subject repeated-measures ANOVA was conducted (significance set at p < 0.05). High-fatigue exercise produced significantly higher PPT at the quadriceps than quiet rest after each set (F[6,162] = 3.25, p < 0.01, partial eta2 = 0.11). During low-fatigue exercise, individuals with an efficient endogenous pain inhibitory capacity displayed significantly higher PPT at the trapezius (F[2.14, 55.61] = 3.31, p = 0.03, partial eta2 = 0.11). Lower fear of pain was moderately associated with greater PPT increases at the trapezius (r = -0.38, p = 0.04). Although high-fatigue exercise produces immediate local hypoalgesia, systemic hypoalgesia is affected by variability in pain inhibition and fear of pain.

Synthesis and Analgesic Properties of Prodrug Bipharmacophore Compounds Based on Pyridoxine and Ketorolac

Prodrug bipharmacophore anti-inflammatory compounds based on pyridoxine and ketorolac were synthesized. A new laboratory method was developed to achieve &gt; 98 % purity of these compounds, without the use of column chromatography. Compared to ketorolac tromethamine, which is the most potent non-opioid analgesic, both compounds exhibited lower toxicity (LD50 &gt; 2000 mg/kg), while maintaining comparable analgesic efficacy in a model of acute thermal pain response.

Bio-Inspired P-type TeSeOx Synaptic Transistor Based on Multispectral Sensing for Neuromorphic Visual Multilevel Nociceptor.

The development of neuromorphic color vision has significant research implications in the fields of machine vision and artificial intelligence. By mimicking the processing mechanisms of energy-efficient biological visual systems, it offers a unique potential for real-time color environment perception and dynamic adaptability. This paper reports on a multispectral color sensing synaptic device based on a novel p-type TeSeOx transistor, applied to a neuromorphic visual multilevel nociceptor. Due to the intrinsic properties of TeSeOx, its narrow bandgap allows for multi-wavelength (405, 532, 655 nm) response, and its oxide semiconductor-based persistent photoconductivity converts optical signals into stored electrical signals, successfully emulating key synaptic characteristics such as excitatory postsynaptic current (EPSC), multi-pulse facilitation, and the transition from short-term to long-term memory. Additionally, it simulates learning, forgetting, and relearning behaviors, as well as image memory under tricolor light. Finally, using optical signals as a pain stimulus, the fundamental functions of a nociceptor are realized, including "threshold," "non-adaptation," "relaxation," and "nociceptive sensitization". More importantly, by using tricolor light, multilevel pain perception is acheived. These results have the potential to advance fields such as autonomous driving, machine vision, and intelligent alert systems.

Comparison between ultrasound guided erector spinae plane block and paravertebral block on acute and chronic post mastectomy pain after modified radical mastectomy: randomized controlled trial

BackgroundInadequate acute postoperative pain management is linked to the effect on the stress response and development of chronic pain. A unique regional anaesthetic method that is becoming more important for postoperative pain management is erector spinea plane block (ESP). Since its initial description, physicians have questioned weather this novel easy method can take the place of paravertebral block (PVB). Our goal was to evaluate, in contrast to control group, the effects of ESP & PVB on acute and chronic post-mastectomy pain.MethodsOne hundred and five female patients undergoing modified radical mastectomy participated in this study, randomly allocated into three equal groups: erector spinae plane block (ESP), thoracic paravertebral (TPV), and control groups. Both blocks were ultrasound-guided with 20 ml 0.25% bupivacaine according to patients’ group, control group was administered standard general anaesthesia without intervention. Total morphine consumption in the first 24 h postoperative was the primary outcome. The secondary outcomes were time to the first analgesia, (Visual Analogue Scale)VAS score, serum level of cortisol and prolactin, sedation score, side effects, and LANSS scores in the first, third, and sixth postoperative months were among the variables compared between groups.ResultsTotal morphine consumption in the first 24 h was significantly higher in control than ESP and TPV groups (10.74 ± 1.37, 8.17 ± 1.69, 5.70 ± 1.95 respectively p < 0.001). Time to first analgesic request was the shortest in control versus ESP and TPV groups as (4.37 ± 3.06, 8.13 ± 1.75, 10.64 ± 1.83 h respectively p ˂0.001). ESP and TPV had significantly lower cortisol and prolactin levels compared to control (p < 0.001). The highest LANSS scores were in the control group in the first, third, and sixth months compared with ESP and TPV, with no significant difference between ESP and TPV.ConclusionESP and TPV blocks provided superior early postoperative analgesia and reduced stress response compared to the control group in female patients undergoing modified radical mastectomy. PVB is better than ESB in acute postoperative pain management (the total morphine consumption VAS score and time of first analgesic request). Both techniques showed better long-term outcomes compared to the control group regarding LANSS score in the 6-month follow-up.Trial registrationhttps://www.ClinicalTrials.gov trial registry (identifier NCT04498234 on 04/08/2020).

Improving Brain Metabolite Detection with a Combined Low-Rank Approximation and Denoising Diffusion Probabilistic Model Approach.

In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive technique for monitoring brain metabolites. However, it is challenged by a low signal-to-noise ratio (SNR), often necessitating extended scan times to compensate. One of the conventional techniques for noise reduction is signal averaging, which is inherently time-consuming and can lead to participant discomfort, thus posing limitations in clinical settings. This study aimed to develop a hybrid denoising strategy that integrates low-rank approximation and denoising diffusion probabilistic model (DDPM) to enhance MRS data quality and shorten scan times. Using publicly available 1H MRS datasets from 15 subjects, we applied the Casorati SVD and DDPM to obtain baseline and functional data during a pain stimulation task. This method significantly improved SNR, resulting in outcomes comparable to or better than averaging over 32 signals. It also provided the most consistent metabolite measurements and adequately tracked temporal changes in glutamate levels, correlating with pain intensity ratings after heating. These findings demonstrate that our approach enhances MRS data quality, offering a more efficient alternative to conventional methods and expanding the potential for the real-time monitoring of neurochemical changes. This contribution has the potential to advance MRS techniques by integrating advanced denoising methods to increase the acquisition speed and enhance the precision of brain metabolite analyses.