Central Pain Research Articles

Association between central sensitization, pain sensitivity and balance control in patients with migraine.

Balance alterations are prevalent among pain conditions, including migraine. The mechanisms explaining the association between pain and balance are unclear, as well as whether levels of pain sensitivity correlate with impaired balance. Our aim was therefore to investigate the association between balance, central sensitization symptoms and pain sensitivity in patients with migraine. This cross-sectional study included 50 patients and demographic, clinical information, central sensitization inventory (CSI) and pain catastrophizing (PCS) scores were obtained. Patients underwent a standardized protocol evaluating balance and pain thresholds for cold (CPT), heat (HPT), mechanical (MPT) and pressure (PPT) in trigeminal (V1) and extra-trigeminal (C6) dermatomes. Data were analysed using Person's correlation, linear regression models and contrasting the presence and absence of central sensitization symptoms through T-tests. Mild-to-moderate correlations were observed between balance and MPT in V1 (r = -0.24, p = 0.046) and C6 (r = -0.41, p = 0.002), CPT in V1 (r = 0.31, p = 0.026), CSI scores (r = 0.27, p = 0.029) and migraine frequency (r = 0.25, p = 0.040). Balance was explained by CPT and MPT (R2 = 0.32, p = 0.001). The variance of CSI was explained by PCS scores and balance (R2 = 0.28, p = 0.001). Patients with symptoms of central sensitization presented an increased balance impairment (p = 0.044) and higher catastrophizing levels (p = 0.001) in contrast to patients without symptoms. Balance impairment is associated with reduced pain thresholds and higher CSI scores. These results may help to elucidate the aetiology of balance alterations among chronic pain conditions. For the first time, it has been shown that balance alterations can reflect greater pain sensitivity and signs of central sensitization in patients with migraine. This opens up perspectives for future studies to understand the mechanisms and further factors associated with balance and pain sensitivity in migraine.

Problems of diagnosis and treatment of chronic pain syndrome in patients with variants of the structure of peripheral nerves. A series of clinical cases

AIM: To assess the presence of variants of the structure of peripheral nerves as possible risk factors for chronic pain syndrome on the example of a series of clinical cases.
 MATERIALS AND METHODS: The systematization and analysis of data from domestic and foreign literature on pathophysiology, clinic, diagnosis and treatment of complex regional pain syndrome has been carried out. Research method: system analysis, presentation of a series of clinical cases.
 RESULTS: A series of clinical cases is presented. The main risk factors for chronic pain syndrome are presented. The conditions and diseases that need to be differentially diagnosed if complex regional pain syndrome is suspected are systematized: tunnel syndromes (carpal tunnel syndrome), diabetic polyneuropathy, HIV polyneuropathy, postherpetic neuralgia, neurogenic claudication/lumbar stenosis, central post-stroke pain, upper thoracic syndrome apertures.
 CONCLUSION: Today, practitioners and neurophysiologists are not sufficiently aware of the existence of interneural anastomoses and features, typical electroneuromyographic signs, as a result of which in most cases the obtained electroneuromyographic data are interpreted erroneously. Variants of the structure of nerves can give an incorrect clinical picture of the condition of peripheral nerves and lead to untimely diagnosis and treatment of chronic pain syndrome, complex regional pain syndrome. Improvements in diagnostic methods, as well as widely introduced high-tech examination methods, in particular electroneuromyography, magnetic resonance imaging and ultrasound, are helping to increase the frequency of detection of abnormalities in the structure of peripheral nerves. In the presented clinical cases, patients had structural variants that gave an incorrect clinical picture of the condition of the peripheral nerves and led to untimely diagnosis and treatment — the development of chronic pain syndrome.

Comparative effects of patient-specific 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy

BackgroundLow back pain (LBP) resides as a most common type of symptom pointing towards lumber radiculopathy. It is defined as burning sharp leg pain that originates from the back and goes all the way down your legs and extends into the toes and foot. Lumbosacral radiculopathy is caused by pathology of the intervertebral disk or associated structures. Different dimensional traction has been used to treat lumbar radiculopathy. This study aimed to compare the effects of 3-dimensional and 2-dimensional lumbar traction on pain and functional disability in patients with lumbar radiculopathy. The randomized clinical trial study of 4 weeks was carried out at the Lifeline Health Care Imaging and Pain Center and the Hamza Hospital Lahore. Twenty-six subjects were included in the clinical trial and divided into two groups after randomization. Group A received three-dimensional lumbar traction with traction force 50% of total body weight on Spine MT 3D traction machine, and group B received two-dimensional lumbar traction with traction force 50% of total body weight. Pre- and post-values of NPRS and ODI were noted.ResultsParametric tests were used during statistical analysis because data was normally distributed. NPRS pre- and posttreatment values showed significant results with p-value < 0.05. ODI pre- and post-values were also obvious with p-value < 0.05. Independent sample T-test was used to assess across the group comparison, suggesting that both groups showed significant improvements of NPRS and ODI post-treatment with p-value (< 0.001).ConclusionThe study concluded that 3D traction significantly reduced pain levels and improved functional impairment more effectively than 2D traction in patients with lumbar radiculopathy.Trial registrationTrial was registered with ClinicalTrials.gov: NCT05356689.

Fibromyalgia is associated with hypersensitivity but not with abnormal pain modulation: evidence from QST trials and spinal fMRI.

Widespread pain and hyperalgesia are characteristics of chronic musculoskeletal pain conditions, including fibromyalgia syndrome (FM). Despite mixed evidence, there is increasing consensus that these characteristics depend on abnormal pain augmentation and dysfunctional pain inhibition. Our recent investigations of pain modulation with individually adjusted nociceptive stimuli have confirmed the mechanical and thermal hyperalgesia of FM patients but failed to detect abnormalities of pain summation or descending pain inhibition. Furthermore, our functional magnetic resonance imaging evaluations of spinal and brainstem pain processing during application of sensitivity-adjusted heat stimuli demonstrated similar temporal patterns of spinal cord activation in FM and HC participants. However, detailed modeling of brainstem activation showed that BOLD activity during "pain summation" was increased in FM subjects, suggesting differences in brain stem modulation of nociceptive stimuli compared to HC. Whereas these differences in brain stem activation are likely related to the hypersensitivity of FM patients, the overall central pain modulation of FM showed no significant abnormalities. These findings suggest that FM patients are hyperalgesic but modulate nociceptive input as effectively as HC.

Acute on Chronic Presentation of Trigeminal Neuralgia

Trigeminal neuralgia (TN) is characterized by sudden, severe, brief, stabbing, usually unilateral, and recurrent pain within one or more branches of the trigeminal nerve. It is divided into three types: (1) primary or classical TN, which requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression, (2) secondary to other identifiable neurologic causes such as multiple sclerosis and intracranial space-occupying lesion, and (3) idiopathic, in which the etiology is unknown. Treatment and prognosis depend on the type. We present this case of an elderly woman with an unusual presentation of TN in a previously diagnosed case. The episodes were increasing in severity and duration, not responding to medical management, allodynia and constant pain was present, and they were accompanied by uncontrolled hypertension. These features strongly suggested other likely causes such as intracranial space-occupying lesions, multiple sclerosis, and central pain. Expert consultations from physicians and neurologists were sought for control of hypertension and reaching a diagnosis. Magnetic resonance angiogram of the brain was done and a diagnosis of classical TN with persistent background facial pain was established. The treatment was successfully done by radiofrequency ablation of the Gasserian ganglion. The pain and blood pressure responded to the treatment.

Central Sensitization in Patients with Chronic Pain Secondary to Carpal Tunnel Syndrome and Determinants.

Central sensitization (CS) is commonly seen in chronic pain disorders, including neuropathic pain. However, there exist inconsistencies concerning the presence of CS in chronic pain secondary to carpal tunnel syndrome (CTS). CS and neuropathic pain manifestations in CTS remain not well established. Therefore, this study aims to investigate the CS and pain profiles in patients with CTS and to explore the potential determinants associated with CS. Patients with suspected CTS symptoms lasting 3 months or above and healthy controls were enrolled. History, physical examinations, and nerve conduction studies were employed to confirm the diagnosis and severity of median nerve dysfunction. The central sensitization inventory (CSI) was used to screen CS. Other outcomes included neuropathic pain, CTS-specific symptom severity and functions, emotion, and health-related quality of life. Between-group comparisons were conducted in terms of the CS presence. Logistic regression analysis was performed to identify determinants associated with CS. Over 60% of participants with CTS were found with clinical CS, significantly higher than that in the control group. More than 70% of the CTS participants were identified to have possible or very likely neuropathic pain components. In addition, one-fourth of CTS cases had depression or anxiety. Anxiety was associated with an increased risk of developing CS in CTS (adjusted OR=1.31, 95% CI 1.08-1.59), whereas higher self-perceived general health rating was negatively associated with the presence of CS (adjusted OR=0.92, 95% CI 0.88-0.97) in the multivariate adjusted regression model. CS is prevalent in patients with CTS. Predominant neuropathic pain characteristics were uncovered in CTS patients as well as comorbid psychological distress. Significant association was found between anxiety and CS presence. Self-perceived general health was inversely related to CS. Further research is warranted to explore the mechanisms of anxiety and central pain processing in painful entrapment neuropathy.

The interrater and test-retest reliability of 3 modalities of quantitative sensory testing in healthy adults and people with chronic low back pain or rheumatoid arthritis.

Quantitative Sensory Testing (QST) modalities used to assess central pain mechanisms require different protocols in people with different musculoskeletal conditions. We aimed to explore the possible effects of musculoskeletal diagnosis and test site on QST interrater and test-retest reliability. The study included participants with rheumatoid arthritis (RA, n = 18; QST conducted on lower leg) and low back pain (LBP, n = 25; QST conducted on forearm), plus 45 healthy control participants (n = 20 QST on lower leg and n = 25 QST on forearm). Test-retest reliability was assessed from QST conducted 1 to 3 weeks apart. Quantitative sensory testing modalities used were pressure pain detection threshold (PPT) at a site distant to tissue pathology, temporal summation (TS), and conditioned pain modulation (CPM). Temporal summation was calculated as difference or ratio of single and repeated punctate stimuli and unconditioned thresholds for CPM used single or mean of multiple PPTs. Intraclass correlation coefficients (ICCs) were compared between different subgroups. High to very high reliability was found for all assessments of PPT and TS across anatomical sites (lower leg and forearm) and participants (healthy, RA, and LBP) (ICC ≥ 0.77 for PPT and ICC ≥ 0.76 for TS). Reliability was higher when TS was calculated as a difference rather than a ratio. Conditioned pain modulation showed no to moderate reliability (ICC = 0.01-0.64) that was similar between leg or forearm, and between healthy people and those with RA or LBP. PPT and TS are transferable tools to quantify pain sensitivity at different testing sites in different musculoskeletal diagnoses. Low apparent reliability of CPM protocols might indicate minute-to-minute dynamic pain modulation.

A second dimension of somatosensory system injury? Thalamic volume loss and neuropathic pain in adults with cerebral palsy and periventricular white matter injury.

Lemniscal (motor-related) and spinothalamic (neuropathic pain-related) somatosensory abnormalities affect different subsets of adults with cerebral palsy (CP). Lemniscal/motor abnormalities are associated with posterior thalamic radiation white matter disruption in individuals with CP and white matter injury. We tested the hypothesis that neuropathic pain symptoms in this population are rather associated with injury of the somatosensory (posterior group nuclei) thalamus. In this cross-sectional study, communicative adults with CP and bilateral white matter injury and neurotypical control participants volunteered to self-report pain symptoms and undergo research MRI. Posterior group thalamic nuclei volume was computed and correlated against neuropathic pain scores. Participants with CP (n=6) had, on average, 24% smaller posterior group thalamic volumes (95% CI [10-39%]; corrected p=0.01) than control participants. More severe volume loss was correlated with more severe neuropathic pain scores (ρ=-0.87 [-0.99,-0.20]; p=0.02). Association with thalamic volume loss suggests that neuropathic pain in adults with CP may frequently be central neuropathic pain. Complementing assessments of white matter microstructure, regional brain volumes hold promise as diagnostic biomarkers for central neuropathic pain in individuals with structural brain disorders.

Myeloid Cell Association with Spinal Cord Injury-Induced Neuropathic Pain and Depressive-like Behaviors in LysM-eGFP Mice

Spinal cord injury (SCI) affects ∼500,000 people worldwide annually, with the majority developing chronic neuropathic pain. Following SCI, approximately 60% of these individuals are diagnosed with comorbid mood disorders, while only ∼21% of the general population will experience a mood disorder in their lifetime. We hypothesize that nociceptive and depressive-like dysregulation occurs after SCI and is associated with aberrant macrophage infiltration in segmental pain centers. We completed moderate unilateral C5 spinal cord contusion on LysM-eGFP reporter mice to visualize infiltrating macrophages. At 6-weeks post-SCI, mice exhibit nociceptive and depressive-like dysfunction compared to naïve and sham groups. There were no differences between the sexes, indicating that sex is not a contributing factor driving nociceptive or depressive-like behaviors after SCI. Utilizing hierarchical cluster analysis, we classified mice based on endpoint nociceptive and depressive-like behavior scores. Approximately 59.3% of the SCI mice clustered based on increased paw withdrawal threshold to mechanical stimuli and immobility time in the forced swim test. SCI mice displayed increased myeloid cell presence in the lesion epicenter, ipsilateral C7-8 dorsal horn, and C7-8 DRGs as evidenced by eGFP, CD68, and Iba1 immunostaining when compared to naïve and sham mice. This was further confirmed by SCI-induced alterations in the expression of genes indicative of myeloid cell activation states and their associated secretome in the dorsal horn and dorsal root ganglia. In conclusion, moderate unilateral cervical SCI caused the development of pain-related and depressive-like behaviors in a subset of mice and these behavioral changes are consistent with immune system activation in the segmental pain pathway. PerspectiveThese experiments characterized pain-related and depressive-like behaviors and correlated these changes with the immune response post-SCI. While humanizing the rodent is impossible, the results from this study inform clinical literature to closely examine sex differences reported in humans to better understand the underlying shared etiologies of pain and depressive-like behaviors following central nervous system trauma.

Results From a Prospective, Clinical Study (US-nPower) Evaluating a Miniature Spinal Cord Stimulator for the Management of Chronic, Intractable Pain

BACKGROUND: Chronic, intractable, neuropathic pain is readily treatable with spinal cord stimulation (SCS). Technological advancements, including device miniaturization, are advancing the field of neuromodulation. OBJECTIVES: We report here the results of an SCS clinical trial to treat chronic, low back and leg pain, with a micro-implantable pulse generator (micro-IPG). STUDY DESIGN: This was a single-arm, prospective, multicenter, postmarket, observational study. SETTING: Patients were recruited from 15 US-based comprehensive pain centers. METHODS: This open-label clinical trial was designed to evaluate the performance of the Nalu™ Neurostimulation System (Nalu Medical, Inc., Carlsbad, CA) in the treatment of low back and leg pain. Patients, who provided informed consent and were successfully screened for study entry, were implanted with temporary trial leads. Patients went on to receive a permanent implant of the leads and micro-IPG if they demonstrated a &gt;= 50% reduction in pain during the temporary trial period. Patient-reported outcomes (PROs), such as pain scores, functional disability, mood, patient impression of change, comfort, therapy use profile, and device ease of use, were captured. RESULTS: At baseline, the average pain Visual Analog Scale (VAS) score was 72.1 ± 17.9 in the leg and 78.0 ± 15.4 in the low back. At 90 days following permanent implant (end of study), pain scores improved by 76% (VAS 18.5 ± 18.8) in the leg and 75% (VAS 19.7 ± 20.8) in the low back. Eighty-six percent of both leg pain and low back pain patients demonstrated a &gt;= 50% reduction in pain at 90 days following implant. The comfort of the external wearable (Therapy Disc and Adhesive Clip) was rated 1.16 ± 1.53, on average, at 90 days on an 11-point rating scale (0 = very comfortable, 10 = very uncomfortable). All PROs demonstrated statistically significant symptomatic improvement at 90 days following implant of the micro-IPG. LIMITATIONS: Limitations of this study include the lack of long-term results (beyond 90 days) and a relatively small sample size of 35 patients who were part of the analysis; additionally, there was no control arm or randomization as this was a single-arm study, without a comparator, designed to document the efficacy and safety of the device. Therefore, no direct comparisons to other SCS systems were possible. CONCLUSIONS: This clinical study demonstrated profound leg and low back pain relief in terms of overall pain reduction, as well as the proportion of therapy responders. The study patients reported the wearable aspects of the system to be very comfortable. KEY WORDS: Spinal cord stimulation, chronic pain, radiculopathy, micro-IPG, battery-free, persistent spinal pain syndrome, failed back surgery syndrome, low back pain, leg pain

A validation study of the Cantonese Chinese version of short form McGill pain questionnaire 2 in Cantonese-speaking patients with chronic pain in Hong Kong.

The study tests the reliability and validity of the Cantonese Chinese version of Short Form McGill Pain Questionnaire 2 (SF-MPQ-2-CC). The original Short Form McGill Pain Questionnaire (SF-MPQ-2) was translated into Cantonese Chinese version. Cantonese-speaking chronic pain patients from three pain centers in Hong Kong were recruited and asked to complete SF-MPQ-2-CC, validated Chinese versions of Identification Pain questionnaire (ID Pain), Pain Catastrophizing Scale (PCS), and Short Form Health Survey (SF-36) for evaluation of convergent and divergent validity, 2 weeks apart for evaluation of internal consistency. A total of 333 and 197 participants completed the first and second set of questionnaires, respectively. SF-MPQ-2-CC was shown to have excellent internal consistency, with an overall Cronbach's alpha value of 0.933. The overall correlation coefficient was 0.875 that shows good test-retest reliability. Construct validity was evaluated using confirmatory factor analysis, where a seconder-order factor model demonstrated a good fit with our data (χ2 = 826.51, p < 0.001, CFI = 0.92, TLI = 0.908, RMSEA = 0.097; SRMR = 0.063; error terms adjusted). SF-MPQ-2-CC also showed good convergent validity with Chinese versions of ID Pain (neuropathic pain) and PCS (continuous pain), and divergent validity was shown by a negative correlation with Chinese version of SF-36. Our study demonstrated that SF-MPQ-2-CC is a valid and reliable pain assessment tool for Cantonese-speaking patients in Hong Kong with a wide range of chronic pain conditions. It also helps to identify the presence of neuropathic pain and negative pain cognition among respondents.

Overview on Juvenile Primary Fibromyalgia Syndrome

JPFS (juvenile primary fibromyalgia syndrome) is a musculoskeletal pain illness that affects children and adolescents. The intricacy of the clinical picture in JPFS has not been adequately characterized in the literature. JFMS symptoms are sometimes difficult to compare to adult fibromyalgia syndrome since many of them are "medically unexplained" and frequently overlap with other medical disorders. The etiology of the illness is multifaceted, with impaired central pain processing being a significant contributor. Musculoskeletal pain that is severe and pervasive is the defining symptom. Other signs and symptoms include headaches, stiffness, subjective joint swelling, sleep and mood disorders, and headaches. Multiple sensitive spots might be found during a physical examination. The diagnosis has certain criteria and is clinical. Early detection and treatment are crucial. The gold standard of care combines a variety of modalities, but most significantly, exercise and cognitive behavioral therapy. The outlook varies, and symptoms might last well into adulthood. Discussing the epidemiology, etiology, pathophysiology, clinical symptoms, diagnosis, and management of JPFS is the goal of the review.

Study will use OTP to look at methadone reform

A new study funded by the National Institute on Drug Abuse (NIDA) and headed by researchers interested in changing the way methadone for opioid use disorder is utilized will use Community Medical Services treatment staff and patients as research subjects. Community Medical Services operates more than 60 opioid treatment programs in 11 states, and is the first OTP, or methadone clinic, to be open around the clock in some areas, with head Nicholas Stavros incorporating novel ways to reach out to patients. The MPACT (Methadone Patient Access to Collaborative Treatment) study will develop and test a medical intervention using a $1 million NIDA grant. Researchers at the University of Arizona Health Sciences, under the direction of Beth Meyerson, Ph.D., will test a “patient‐empowered, trauma‐informed” treatment using methadone in Arizona. Meyerson is a professor, and director of the Harm Reduction Research Lab in the University of Arizona College of Medicine at Tucson. The study will take two years. “Improving methadone treatment is critical because one person dies from an opioid overdose every five minutes in this country,” said Meyerson, who is also director of policy for the University of Arizona Health Sciences Comprehensive Pain and Addiction Center. “Access to methadone has been found to reduce opioid overdoses by 80%, but it is currently being delivered in ways that can create suboptimal patient outcomes, where only 30% of patients complete treatment and over 30% experience significant treatment interruptions.” The protocol will be used to focus on how to make treatment more acceptable to patients and includes a staff‐focused intervention to reduce trauma related to actually working in the OTP. “Vicarious trauma has been found to impact both patient care and staff recognition of the need to adopt treatment and practice innovations,” Meyerson said, adding, “This study is the crucial first step in assessing MPACT's feasibility, acceptability and preliminary effects on patient and staff outcomes. Once our established milestones are reached from the pilot program, the second phase of funding will enable us to expand the study of MPACT among 30 clinics with 600 patients and 450 staff members across the U.S.” Kristen Rundell, M.D., professor and chair of the Department of Family and Community Medicine at the University of Arizona, where Meyerson's harm reduction lab is based, said the study “is a prime example of our department's emphasis of social justice through medicine.”

Central Sensitization and Neuropathic Pain Cumulatively Affect Patients Reporting Inferior Outcomes Following Total Knee Arthroplasty.

This article was updated on November 17, 2023, because of previous errors, which were discovered after the preliminary version of the article was posted online. On page 102, the text that had read "In a post hoc analysis of the preoperative results, Group 1 showed significantly inferior WOMAC pain, function, and total scores compared with Group 4 (p < 0.05 for all). Groups 2 and 3 showed worse preoperative WOMAC pain, function, and total subscores compared with Group 4 (p < 0.05 for all). These results remained the same at 2 years after surgery." now reads "In a post hoc analysis of the preoperative results, Groups 1, 2, and 3 showed significantly inferior WOMAC pain, function, and total scores compared with Group 4 (p < 0.05 for all). At 2 years postoperatively, Group 1 showed inferior WOMAC pain, function, and total scores compared with the other groups (p < 0.05 for all). Also, Groups 2 and 3 had worse WOMAC pain, function and total scores compared with Group 4 (p < 0.05 for all)." Also, on page 106, the title of Table IV, which had previously read "Inter-Group Comparison of Preoperative Scores (Post Hoc Analysis)" now reads "Inter-Group Comparison of Postoperative Scores (Post Hoc Analysis)."

Abstract 18106: Keeping up With the Newest Guideline Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction, Resident-Driven Quality Improvement Project

Introduction: Chronic Heart Failure (CHF) is an epidemic associated with high morbidity and mortality. As per 2022 AHA/ACC/HFSA guidelines, the management of Heart Failure with reduced Ejection Fraction (HFrEF) includes Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), Angiotensin-Converting Enzyme Inhibitors (ACEIs)/Angiotensin Receptor Blockers (ARBs), Beta-Blockers (BB), Mineralocorticoid Receptor Antagonists (MRA) and Sodium-Glucose co-transporter 2 Inhibitors (SGLT2I) as class 1 recommendations. Considering the new guidelines for HFrEF we decided to perform a quality improvement project to improve the GDMT prescription rate in patients with HFrEF. Methods: Our project included: dot phrase creation for all physicians through electronic medical records (EMR) system, educational sessions, monthly emails and weekly EMR chat messages regarding GDMT and CHF order set to physicians, A4 sized posters distributed on all hospital floors. We then performed retrospective review and analysis of patient charts who were admitted to three UPMC Central PA hospitals with diagnosis of HFrEF exacerbation during December 2019 to January 2021 (pre-intervention) and March 2022 to September 2022 (post-intervention). Results: Total 615 patients were included. There were no significant differences in demographics between pre intervention (357) and post intervention (258) groups including age, sex, race. There were no differences in prescription rate and target dose at discharge between BB groups (92.72% vs 91.86%%, p=0.693 and 7.25% vs 7.17%, p=0.978). The intervention helped in increasing prescription of ARNIs from 6.2% to 30.62%, p&lt; 0.0001 and 13.92% were discharged on target dosages. The prescription of MRA was increased (47.62%vs 51.55%). Furthermore, initiation of SGLT2I was achieved in 41.47% in post-intervention from 0% in the pre-intervention group. Conclusions: Despite higher awareness of GDMT and the trend towards having more patients discharged on therapeutic dosages of GDMT, it is evident that GDMT is still underused among patients with HFrEF. Our results indicate that more emphasis should be placed on rapid up-titration of GDMT.

Can a structured home-based rehabilitation program reduce dorsal central wrist pain?

ObjectivesDorsal central wrist pain, often a consequence of peri-scapholunate ligament injury, can result in a decline in functional performance. There is a scarcity of clinical data evaluating the effectiveness of conservative management on peri-scapholunate ligament injury. Conservative management includes education, immobilization with orthotic devices, scapholunate-stabilizing muscle strengthening, and proprioception training. The identification of the ligamento-muscular reflex and scapholunate-stabilizing muscles formed the rationale for a rehabilitation training program. We have devised an innovative standardized 16-week treatment program for patients with dorsal central wrist pain associated with acute peri-SL ligament injury. We hypothesized that the program can effectively reduce dorsal wrist pain and improve functional performance. Materials and methodsRecruited subjects underwent the 16-week home-based program, which included immobilization and rehabilitation exercises, to improve their wrist stability. Follow-up was arranged every 4 weeks for progress monitoring. The Short-Form 12 item questionnaire version 2, power grip, pinch grip, wrist range of motion, total performance score and total pain score when performing activities of daily living were used to evaluate the effectiveness of the program. An exercise adherence questionnaire was used to evaluate adherence to the home rehabilitation program. ResultsTwenty-three subjects (26 wrists) completed the program. Pain on visual analog scale improved by 5.1 cm and total pain score improved from 14.4/20 to 19.5/20. Total performance score reached 39/40, which indicated near-normal wrist function. Power grip and pinch grip increased by 22.3% and 17.8%, respectively. The physical component scale of the Short-Form 12 item questionnaire showed significant improvement, while the mental component scale did not. Overall adherence was fair. DiscussionConservative management, including immobilization and rehabilitation training, can provide significant clinical improvement in patients with dorsal central wrist pain associated with acute peri-scapholunate ligament injury. ConclusionStandardized wrist rehabilitation can be taken as a reference treatment modality. It is an evidence-based non-invasive treatment option for clinicians and therapists.

A Novel Endoplasmic Reticulum-Targeted Metal-Organic Framework-Confined Ruthenium (Ru) Nanozyme Regulation of Oxidative Stress for Central Post-Stroke Pain.

Central post-stroke pain (CPSP) is a chronic neuropathic pain caused by cerebrovascular lesion or disfunction after stroke. Convincing evidence suggest that excessive reactive oxygen species (ROS), generated matrix metalloproteinase (MMPs) and neuroinflammation are largely involved in the development of pain. In this study, an effective strategy is reported for treating pain hypersensitivity using an endoplasmic reticulum (ER)-targeted metal-organic framework (MOF)-confined ruthenium (Ru) nanozyme. The Ru MOF is coated with a p-dodecylbenzene sulfonamide (p-DBSN) modified liposome with endoplasmic reticulum-targeted function. The experimental results reveals that ROS, Emmprin, MMP-2, and MMP-9 are upregulated in the brain of CPSP mice, along with the elevated expression of inflammation markers such as TNF-α and IL-6. Compared to vehicle, one-time intravenous administration of ER-Ru MOF significantly reduces mechanical hypersensitivity after CPSP for three days. Overall, ER-Ru MOF system can inhibit oxidative stress in the brain tissues of CPSP model, reduce MMPs expression, and suppress neuroinflammation response-induced injury, resulting in satisfactory prevention and effective treatment of CPSP during a hemorrhagic stroke. The ER-Ru MOF is expected to be useful for the treatment of neurological diseases associated with the vicious activation of ROS, based on the generality of the approach used in this study.

Neural correlates of central pain sensitization in chronic low back pain: a resting-state fMRI study.

The objective of this study is to explore the neural correlates of pain sensitization in patients with chronic low back pain (cLBP). While the association between cLBP and pain sensitization has been widely reported, the underlying brain mechanism responsible for this relationship requires further investigation. Our study included 56 cLBP patients and 56 healthy controls (HC). Functional magnetic resonance imaging data were obtained, and the voxel-wise amplitude of low-frequency fluctuation (ALFF) was calculated to identify brain alterations in cLBP patients compared to HC groups. Pearson correlation coefficients were computed to explore the association between clinical data and brain alterations. Furthermore, mediation analyses were performed to investigate the path association between brain alterations and pain-related behaviors. Our findings revealed that patients with cLBP exhibited higher sensitivity, attention, and catastrophizing tendencies towards pain compared to HC. Furthermore, cLBP patients displayed significantly higher ALFF in various brain regions within the "pain matrix" and the default mode network when compared to HC. The altered precuneus ALFF was positively correlated with pain intensity (R = 0.51, P<0.001) and was negatively correlated with pain sensitivity (R = -0.43, P<0.001) in cLBP patients. Importantly, the effect of altered precuneus ALFF on pain intensity was mediated by pain threshold in these patients. Our study suggests that altered neural activity in the precuneus may contribute to pain hypersensitivity, which further exacerbating pain in cLBP patients.

Pain in Colorectal Surgery: How Does It Occur and What Tools Do We Have for Treatment?

Pain is a complex entity with deleterious effects on the entire organism. Poorly controlled postoperative pain impacts the patient outcome, being associated with increased morbidity, inadequate quality of life and functional recovery. In the current surgical environment with less invasive surgical procedures increasingly being used and a trend towards rapid discharge home after surgery, we need to continuously re-evaluate analgesic strategies. We have performed a narrative review consisting of a description of the acute surgical pain anatomic pathways and the connection between pain and the surgical stress response followed by reviewing methods of multimodal analgesia in colorectal surgery found in recent literature data. We have described various regional analgesia techniques and drugs effective in pain treatment, emphasizing their advantages and concerns. We have also tried to identify present knowledge gaps requiring future research. Our review concludes that surgical pain has peculiarities that make its management complex, implying a consistent, multimodal approach aiming to block both peripheral and central pain pathways.

Ac4C Enhances the Translation Efficiency of Vegfa mRNA and Mediates Central Sensitization in Spinal Dorsal Horn in Neuropathic Pain.

N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional machinery with extensive existence for RNA modification, plays versatile roles in various cellular processes and functions. However, the molecular mechanism by which ac4C modification mediates neuropathic pain remains elusive. Here, it is found that the enhanced ac4C modification promotes the recruitment of polysome in Vegfa mRNA and strengthens the translation efficiency following SNI. Nerve injury increases the expression of NAT10 and the interaction between NAT10 and Vegfa mRNA in the dorsal horn neurons, and the gain and loss of NAT10 function further confirm that NAT10 is involved in the ac4C modification in Vegfa mRNA and pain behavior. Moreover, the ac4C-mediated VEGFA upregulation contributes to the central sensitivity and neuropathic pain induced by SNI or AAV-hSyn-NAT10. Finally, SNI promotes the binding of HNRNPK in Vegfa mRNA and subsequently recruits the NAT10. The enhanced interaction between HNRNPK and NAT10 contributes to the ac4C modification of Vegfa mRNA and neuropathic pain. These findings suggest that the enhanced interaction between HNRNPK and Vegfa mRNA upregulates the ac4C level by recruiting NAT10 and contributes to the central sensitivity and neuropathic pain following SNI. Blocking this cascade may be a novel therapeutic approach in patients with neuropathic pain.