Central Pain Research Articles

Discriminating fingerprints of chronic neuropathic pain following spinal cord injury using artificial neural networks and mass spectrometry analysis of female mice serum

Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.

ID: 334170 Case Report: Spinal cord stimulation in the treatment of central pain syndrome ()

ID: 334170 Case Report: Spinal cord stimulation in the treatment of central pain syndrome ()

The effects of C-tactile stimulation on temporal summation of second pain: A study of the central and peripheral neural correlates

Affective touch is mediated by specialized receptors sensitive to gentle and slow touch called C-tactile afferents (CT). The activation of these receptors has shown promise in reducing subjective pain ratings, however, how this type of touch can affect central sensitization processes is poorly studied. This work aimed to investigate if affective touch is able to modulate pain sensitization and its electrophysiological correlates during Temporal Summation of Second Pain (TSSP), a phenomenon characterized by an increase in pain perception due to repeated noxious stimuli.Thirty-seven participants underwent a TSSP protocol involving three conditions: TSSP alone, TSSP during vibrotactile stimulation, and TSSP during CT stimulation (administered with a brush mounted in a robot arm). We measured subjective pain ratings, electroencephalographic (N2-P2 complex) and electrocardiographic activity during these conditions.Participants reported a significantly lower increase of pain during CT stimulation compared to vibrotactile stimulation, but not to TSSP alone. In addition, TSSP was reduced when administered in the ipsilateral arm compared to the other somatosensory stimulation. Subjective reports of attention towards painful stimuli, amplitude of the N2-P2 complex, and heart rate were also reduced during CT stimulation. Conclusion: Our results indicated that the activation of CT receptors may reduce sensitization compared to other types of somatosensory stimulation, which is possibly related to the reduction of the attention devoted to nociceptive stimulation. Our results suggest that activation of CT receptors may alleviate the occurrence of central pain sensitization.

Association Between Level of Pain and Depression Among Chronically Ill Older Adults in Rural Alabama: A Pilot Study

There is a paucity of research on pain and depression among older adults in rural communities. To address such a gap, this study examined the association between pain and depression among older rural-community-dwelling adults. Recruited from rural senior centers, 100 chronically ill older adults (age 55 or older) experiencing pain completed a cross-sectional survey. Data were collected on their level of depression (a five-item version of the Center for Epidemiologic Studies Depression scale), pain (the six-item Philadelphia Geriatric Center Pain scale), and sociodemographic factors. A multiple linear regression was conducted. With sociodemographic variables controlled, those reporting higher pain scores were significantly more likely to have higher depression scores (p < .05). Older participants had lower depression scores than younger participants (p < .05). In view of poorer health outcomes and limited health care access in rural areas, our findings warrant interventions to promote better access to pain management and mental health services for rural older adults.

Neurotensin-expressing lateral hypothalamic neurons alleviate neuropathic and inflammatory pain via neurotensin receptor signaling

Persistent, severe pain negatively impacts health and wellbeing, but half of patients do not receive adequate relief from current treatments. Understanding signals that modulate central pain processing could point to new strategies to manage severe pain. Administering Neurotensin (Nts) or Nts receptor (NtsR) agonists into the brain provides analgesia comparable to pharmacologic opioids. However, the endogenous sources of Nts that modify pain processing and might be leveraged for pain relief remained unknown. We previously characterized a large population of Nts-expressing neurons in the lateral hypothalamic area (LHANts neurons) that project to brain regions that participate in descending control of pain processing. We hypothesized that LHANts neurons are an endogenous source of Nts and activating them would alleviate pain dependent on Nts signaling via NtsRs. To test this, we injected NtsCre mice in the LHA with AAVs to cre-dependently express either mCherry (Control) or the excitatory hM3Dq in LHANts neurons, permitting their stimulation after treatment with the hM3Dq ligand clozapine N-oxide (CNO). Activating LHANts neurons had no effect on thermal pain and mechanical responses in naïve mice. By contrast, both spared nerve injury- (SNI) and complete Freund’s adjuvant (CFA)-induced mechanical hypersensitivity was completely reversed by CNO-stimulation of LHANts neurons. Pretreatment with the Nts receptor antagonist SR142948 reduced CNO-mediated analgesia, indicating that LHANts neurons alleviate chronic pain in an Nts receptor-dependent manner. Taken together these data identify LHANts neurons as an endogenous source of Nts that modulates central pain processing and may inform future development of Nts-based targets to treat severe pain.

Postsurgical tactile-evoked pain: a role for brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent novel tactile corpuscles.

Millions of people undergo surgical procedures each year with many developing postsurgical pain. Dynamic allodynia can arise when, for example, clothing brushing close to the surgical site elicits pain. The allodynia circuits that enable crosstalk between afferent tactile inputs and central pain circuits have been studied, but the peripheral tactile drive has not been explored. Investigate the innervation of the skin in the rat plantar hindpaw skin-muscle incision model. Incision increased epidermal thickness and cell layers and reduced intraepidermal nerve fibre density, identified with PGP9.5 immunostaining. Strikingly, Collagen IV immunostaining revealed the development of dermal protrusions, oriented towards the incision site, that were reminiscent of the dermal papillae that exist in glabrous footpads. S100 immunostaining for lamellar Schwann cells revealed the presence of novel tactile corpuscles (S100-positive bulb) within incision-induced putative dermal papillae. The occurrence of these novel tactile corpuscles coincided with behavioural observations of dynamic allodynia. Tactile corpuscles require brain-derived neurotrophic factor- tropomyosin receptor kinase B (BDNF-TrkB) signalling to form during development, and an increase in BDNF-immunostaining intensity was observed close to the incision site. Local acute administration of TrkB-Fc, to block BDNF-TrkB signalling, reduced, by approximately 50%, both tactile corpuscle size (S100+ bulb area) and dynamic allodynia. Surgery induces the development of novel tactile corpuscles in the incision surround, in a BDNF-TrKB-dependent manner, that contributes to postsurgical tactile-evoked pain.

CENTRAL POST-STROKE PAIN: A SCOPING REVIEW

Introduction: Central post-stroke pain (CPSP) is a neuropathic pain syndrome that can affect individuals who have suffered a stroke and which is still under-recognized by doctors. CPSP has an estimated prevalence of 11% and is more common in lesions involving the thalamus. Diagnosis is challenging due to the variable clinical manifestations and the lack of specific diagnostic criteria. The study aims to gather up-to-date information on this condition and highlight the importance of its early recognition. Methodology: This is a descriptive review of the literature in Medline databases, including articles from 2014 to 2024. A total of 468 articles were initially found, of which 43 were selected after applying inclusion and exclusion criteria. Results and discussion: Risk factors were identified as involvement of the spinothalamic pathway, presence of sensory deficits, female gender, young age, and initial stroke severity. The clinical characteristics of CPSP include pain and sensory abnormalities in the regions corresponding to the injured brain territory. The differential diagnosis includes other etiologies, such as post-stroke spasticity, complex regional pain syndrome, headache and shoulder pain. CPSP has a significant impact on quality of life and is associated with psychological disorders and functional limitations. Conclusion: It is understood that early recognition and appropriate management of CPSP are essential for improving patients' quality of life, highlighting the need for clear diagnostic criteria and effective treatments.

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury.

In addition to the loss of motor function, ~60% of patients develop pain after spinal cord injury. The cellular-molecular mechanisms are not well understood, but the data suggests that plasticity within the rostral, epicenter, and caudal penumbra of the injury site initiates a cellular-molecular interplay that acts as a rewiring mechanism leading to central neuropathic pain. Sprouting can lead to the formation of new connections triggering abnormal sensory transmission. The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity. Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen. In this study, we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury. We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters, leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting. Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control (placebo). We used von Frey monofilaments and the "up-down method" to evaluate mechanical allodynia. Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sex-dependent effect. The expression profile of glutamatergic transporters (excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1) revealed a sexual dimorphism in the rostral, epicenter, and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes. Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents. Analyses of peptidergic (calcitonin gene-related peptide-α) and non-peptidergic (isolectin B4) fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/ isolectin B4 ratio in comparison with sham, suggesting increased receptive fields in the dorsal horn. Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats, this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury. Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord. The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain, an area with a critical need for treatment.

Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia.

Central sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non-invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS. It addresses controversies about heat sensitivity changes, the role of tactile afferents in mechanical hypersensitivity and detecting SHA through electrical stimuli. Additionally, it reviews the potential of neurophysiological measures to indicate CS presence. Four databases, PubMed, ScienceDirect, Scopus and Cochrane Library, were searched using terms linked to 'hyperalgesia'. The search was limited to research articles in English conducted in humans until 2023. Evidence for heat hyperalgesia in the SHA area is sparse and seems to depend on the experimental method used. Minimal or no involvement of tactile afferents in SHA was found. At the spinal level, the threshold of the nociceptive withdrawal reflex (RIII) is consistently reduced during experimentally induced SHA. The RIII area and the spinal somatosensory potential (N13-SEP) amplitude are modulated only with long-lasting nociceptive input. At the brain level, pinprick-evoked potentials within the SHA area are increased. Mechanical pinprick hyperalgesia is the most reliable behavioural readout for SHA, while the RIII threshold is the most sensitive neurophysiological readout. Due to scarce data on reliability, sensitivity and specificity, none of the revised neurophysiological methods is currently suitable for CS identification at the individual level. Gathering evidence for CS in humans is a crucial research focus, especially with the increasing interest in concepts such as 'central sensitization-like pain' or 'nociplastic pain'. This review clarifies which readouts, among the different behavioural and neurophysiological proxies tested in experimental settings, can be used to infer the presence of CS in humans.

Feasibility of a Novel Movement Preference Approach to Classify Case Complexity for Adults with Non-Specific Chronic Low Back Pain

The non-specific nature of low back pain (LBP) poses challenges in its diagnosis and clinical management. Classifying case complexity with an exercise method may help overcome these challenges. The present study proposed a movement-based classification system based on Dance Medicine Australia (DMA) Clinical Pilates for patients with non-specific chronic LBP. To test the feasibility of the proposed system, 40 adults with non-specific chronic LBP were assessed on their movement preference (i.e., movement directions that can relieve pain or are pain-free) through the DMA Clinical Pilates method. The movement preferences could be a combination of each of the following movement directions: (1) flexion or extension, (2) left or right lateral flexion and/or (3) left or right rotation. For cases that had central or bilateral pain, the number of movement preferences identified was used to guide the classification. Using the proposed system, all 40 (100%) LBP cases were successfully classified into basic (n = 8, 20%), intermediate (n = 17, 42.5%), advanced (n = 8, 20%) or expert (n = 7, 17.5%) levels of complexity. In conclusion, this study has demonstrated that the proposed movement-based classification system was a feasible method for classifying case complexity in adults with non-specific chronic LBP. Future clinical intervention studies are needed to confirm if this classification system can enhance therapeutic outcomes in patients.

Assessment of decision-making autonomy in chronic pain patients: a pilot study

BackgroundPatient decision-making autonomy refers to the patients’ ability to freely exert their own choices and make their own decisions, given sufficient resources and information to do so. In pain medicine, it is accepted that appropriate beneficial management aims to propose an individualized treatment plan shared with the patients, as agents, to help them live as autonomously as possible with their pain. However, are patients in chronic pain centers sufficiently autonomous to participate in the therapeutic decisions that concern them? As this question still remains unanswered, a pilot study was set up to that aim.MethodsOver a 2-month period, first-time patients within a tertiary multidisciplinary pain center underwent a systematic evaluation of their autonomy using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), considered the benchmark tool for measuring a patient’s ability to consent to treatment. Demographic data and pain characteristics of the patients were collected and their respective attending pain physicians were asked to clinically assess their patients’ degree of autonomy. Another physician, who had not participated in the initial patient evaluation, subsequently administered the MacCAT-T questionnaire to the same patients.ResultsTwenty-seven patients were included during the study period (21 women and 6 men), with an average age of 50 years. The average duration of pain was 8 years. Based on their clinical experience, the 4 different pain physicians in charge of these patients considered that out of 25 assessed patients, 22 of them (89%) had full decision-making capacity, with no deficit in autonomy. According to the MacCAT-T results, only 13 of these 25 patients (48%) had no deficit, while 7 (26%) had a major deficit in autonomy. The only patient characteristic that appeared to be related to autonomy was pain type, specifically nociplastic pain. The average time taken to complete the test was 20 min, and patients were very satisfied with the interview.ConclusionResults from the present pilot study suggest that patients suffering from chronic pain do not appear to be entirely autonomous in their decision to consent to the proposed treatment plan according to the MacCAT-T questionnaire, and physicians seem to find it difficult to properly assess this competence in a clinical setting. Further studies with larger samples are needed to better evaluate this concept to improve the complex management of these patients.

24th Panhellenic Congress of Regional Anaesthesia, Pain Management and Palliative Care, September 19-22, 2024

PARIS.SY.A. in collaboration with ESRA HELLAS and the 1st Anesthesiology Clinic - Pain and Palliative Care Center EKPA awaits you at the 24th Panhellenic Congress of Regional Anesthesia, Pain Treatment and Palliative Care, September 19 – 22, 2024, in Lefkada, Greece.

Psychophysical changes after total sleep deprivation and experimental muscle pain.

Sleep disturbances exacerbate chronic pain, increase psychological load, and increase inflammation. Delayed onset muscle soreness (DOMS) mimics aspects of chronic pain, predominantly affecting peripheral pain mechanisms, while experimental sleep provocations have been shown to impact central pain mechanisms. This study aimed to combine a DOMS model with total sleep deprivation (TSD) to create a novel model affecting both peripheral and central pain mechanisms. A total of 30 healthy participants attended two sessions (baseline and follow-up) separated by 24 h of TSD and a home rating after 48 h. Assessments of interleukin 6 (IL-6) levels, sleep quality, pain catastrophising, affect, and symptoms of depression and anxiety were included in the baseline and follow-up sessions. Additionally, pressure pain and tolerance thresholds, temporal summation, and conditioned pain modulation (CPM) were assessed using cuff-pressure algometry in the baseline and follow-up sessions. DOMS was induced with eccentric calf raises during the baseline session followed by 24 h of TSD. At follow-up pain tolerance (p = 0.012) was significantly reduced, and CPM (p = 0.036) was significantly impaired compared to baseline. Psychological changes included decreases in pain catastrophising (p = 0.027), positive affect (p < 0.001), negative affect (p = 0.003), and anxiety (p = 0.012). Explorative regression models predicted 58% and 68% of DOMS pain intensity after 24 and 48 h, respectively, based on baseline body mass index, pain thresholds, psychological measures, and IL-6 (p < 0.01). Combining DOMS with 1 night of TSD induced pain hypersensitivity, impaired CPM, and altered psychological states. A combination of baseline inflammation, psychological measures, and pain sensitivity significantly predicted DOMS pain intensity after 24 and 48 h.

The Cytidine N-Acetyltransferase NAT10 Promotes Thalamus Hemorrhage-Induced Central Poststroke Pain by Stabilizing Fn14 Expression in Thalamic Neurons.

The recognition of RNA N4-acetylcytidine (ac4C) modification as a significant type of gene regulation is growing; nevertheless, whether ac4C modification or the N-acetyltransferase 10 protein (NAT10, the only ac4C "writer" that is presently known) participates in thalamus hemorrhage (TH)-induced central poststroke pain (CPSP) is unknown. Here, we observed NAT10 was primarily located in the neuronal nuclei of the thalamus of mice, with Fn14 and p65. An increase of NAT10 mRNA and protein expression levels in the ipsilateral thalamus was observed from days 1 to 14 after TH. Inhibition of NAT10 by several different approaches attenuated Fn14 and p65 upregulation of TH mice, as well as tissue injury in the thalamus on the ipsilateral side, and the development and maintenance of contralateral nociceptive hypersensitivities. NAT10 overexpression increased Fn14 and p65 expression and elicited nociceptive hypersensitivities in naïve mice. Our findings suggest that ac4C modification and NAT10 participate in TH-induced CPSP by activating the NF-κB pathway through upregulating Fn14 in thalamic neurons. NAT10 could serve as a promising new target for CPSP treatment.

Advancements in Modern Treatment Approaches for Central Post-Stroke Pain: A Narrative Review.

Central post-stroke pain (CPSP) poses a multifaceted challenge in medical practice, necessitating a thorough and multidisciplinary approach for its diagnosis and treatment. This review examines current methods for addressing CPSP, highlighting both pharmacological and non-pharmacological therapies. It covers the mechanisms and clinical effectiveness of these treatments in managing CPSP and emphasizes the importance of personalized treatment plans, given the varied causes of CPSP. Recent advancements have illuminated diverse treatment modalities for CPSP. Pharmacotherapy spans from conventional analgesics to anticonvulsants and antidepressants, tailored to mitigate the neuropathic characteristics of CPSP. Non-pharmacological interventions, including physical therapy and psychological strategies, are pivotal in managing CPSP's chronic nature. For cases resistant to standard treatments, advanced interventions such as nerve blocks and surgical procedures like deep brain stimulation (DBS) or motor cortex stimulation (MCS) are considered. Additionally, innovative technologies such as neuromodulation techniques and personalized medicine are emerging as promising avenues to enhance therapeutic outcomes and improve quality of life for individuals grappling with CPSP. Modern approaches in managing CPSP require an interdisciplinary and patient-centric approach. Customizing treatment plans to address the specific etiology and symptoms of CPSP is crucial. Pharmacotherapy remains fundamental, encompassing medications such as anticonvulsants and antidepressants tailored to manage neuropathic pain. Integrating non-pharmacological interventions is crucial for providing comprehensive care. Additionally, investigating innovative technologies and personalized medicine presents promising opportunities to enhance treatment results and elevate the quality of life for those suffering from CPSP. Ultimately, an integrated approach that acknowledges the multifaceted nature of CPSP is essential for effective management and patient well-being.

SPIDOL study protocol for the assessment of intrathecal ziconotide antalgic efficacy for severe refractory neuropathic pain due to spinal cord lesions

RationaleCentral neuropathic pain resulting from spinal cord injury is notoriously debilitating and difficult to treat with few currently available treatments. A novel molecule with intrathecal administration: Ziconotide has been approved for treatment of refractory neuropathic pain in general. It acts as a presynaptic calcium channel blocker. A pilot study has shown its potential in SCI neuropathic pain patients.ObjectiveThe aim of this study is to determine the long-term (6 months) efficacy of chronic intrathecal ziconotide for the treatment of neuropathic SCI pain.Study designMulticenter, Randomized, Comparative, Placebo controlled, Double blind clinical trial, with a crossover of random alternated periods of 6 months (placebo or ITZ) for a total of 15 months including a total of 44 patients.Study population• Patients with SCI of various etiologies exhibiting neuropathic pain refractory to non-invasive treatments.• > 18 years.InterventionIntrathecal administration of ziconotide via an implanted pump.Study outcomesPrimary study outcomeDifference in pain intensity for all patients between effective treatment and placebo periods.Secondary study outcomes1. Continuous evaluation of pain intensity.2. Percentage of patients with at least 30% of pain reduction.3. Satisfaction level of the patient pain relief.4. Declarations of serious adverse events.5. Duration and intensity of spontaneous and provoked pain.6. Quality of life.7. Patient global impression of change.8. Quantification of daily dosages of analgesic drug intake.9. Long term memory and neurocognitive effects.10. Assessment of the patient’s physical and emotional distress.Nature and extent of the burden and risks associated with participation, benefit, and group relatednessParticipation in this study is in accordance with current treatment protocols for SCI neuropathic pain in France therefore it proposes a treatment that would currently be considered regular practice even though no RCT evidence is yet available. The study gives patients the advantage of directly testing versus placebo a treatment that otherwise entails significant constraints.A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period.

11th revision of the International Classification of Diseases chronic primary pain diagnoses in children and adolescents: representation of pediatric patients in the new classification system.

Chronic pain is common among children and adolescents; however, the diagnoses in the newly developed 11th revision of the International Classification of Diseases (ICD-11) chronic pain chapter are based on adult criteria, overlooking pediatric neurodevelopmental differences. The chronic pain diagnoses have demonstrated good clinical applicability in adults, but to date, no field study has examined these diagnoses to the most specific diagnostic level in a pediatric sample. The current study aimed to explore pediatric representation within the ICD-11, with focus on chronic primary pain. Healthcare professionals (HCPs) at a specialized pediatric pain center documented the symptoms of and assigned both ICD-10 and ICD-11 diagnoses to N = 402 patients. Using criteria-based computer algorithms, specific ICD-11 pain diagnoses were allocated for each documented pain location, with residual diagnoses (ie, "unspecified") assigned if criteria were not (fully) met. Within the ICD-11, the algorithms assigned specific pain diagnoses to most patients (73.6%). In ICD-10, HCPs could not specify a diagnosis for 5.2% of patients; the ICD-11 algorithm allocated a residual chronic primary pain diagnosis in 51.2%. Residual categories were especially prevalent among younger children, boys, patients with headaches, and those with lower pain severity. Overall, clinical utility of the ICD-11 was high, although less effective for chronic back pain and headache diagnoses. The latter also exhibited the lowest agreement between HCPs and algorithm. The current study underscores the need for evidence-based improvements to the ICD-11 diagnostic criteria in pediatrics. Developing pediatric coding notes could improve the visibility of patients internationally and improve the likelihood of receiving reimbursement for necessary treatments through accurate coding.

Abstract MP11: Evaluation of a Remote Patient Monitoring Hypertension Program with Telehealth Pharmacist Management in Nephrology Clinic Patients

Introduction: Remote patient monitoring (RPM) and physician-pharmacist collaborative models have potential in improving hypertension control. Herein, we report the effectiveness of a community based, self-measured blood pressure (SMBP) RPM program on BP control and healthcare utilization in a largely rural health system. Methods: A multidisciplinary team developed a self-measured blood pressure (SMBP) RPM program in central and northeast PA using a virtual platform with bluetooth-connected BP devices targeting patients with BP ≥140/90 mmHg seen in nephrology clinics. From 3/2022 to 9/2022, high BP notifications were transmitted to nephrologists. After 9/2022, BP notifications were transmitted first to pharmacists, who co-managed BP through collaborative practice agreements via telehealth. We captured pharmacist interventions by reviewing electronic health record documentation. Changes in SMBP over time and the effect of pharmacist interventions were analyzed using mixed effects models. All-cause hospitalizations and emergency room (ER) visits were compared in 6-month pre/post-enrollment periods. Results: A total of 205 patients (mean age 62.3y, clinic BP 146/84, 3.1 BP classes, 48% female, 53% CKD) were enrolled into the program and had ≥ 6 months follow-up data. SMBP control &lt;140/90 improved from 30% during week 1 to 67% at 6 months and 74% at 12 months. Overall, systolic SMBP improved over the first 6 months with stronger effect on patients with higher baseline BP (baseline BP ≥150/100 mmHg: -3.3 mmHg/month (95% CI: -3.5, -3.1); baseline 140-149/90-99: -2.4 (95% CI: -2.6, -2.1) mmHg/month; baseline &lt;140/90: -0.6 (-0.9, -0.4) mmHg/month). Pharmacist telehealth encounters were documented in 65% of patients; 46% had a BP medication adjustment; 37% had new BP medication classes, including 9% mineralocorticoid receptor antagonist. Pharmacist medication intervention was associated with greater decline in systolic BP over time (-1.3 mmHg/month; 95% CI: -1.6, -1.1). Comparing the 6 months pre vs. post-enrollment, patients experienced a reduction in hospitalizations (6.0% vs. 0%; Exact Mcnemar p=0.0005) and no difference in ER visits (14.9% vs. 12.9%; p=0.6). Conclusion: Participation in a nephrologist-pharmacist SMBP RPM program was associated with improvement in BP control and reduced hospitalizations. Future efforts are underway to refine delivery of this program for the largest impact on improving BP control.

Хроническая боль в спине: от патогенеза к адекватной фармакотерапии

Chronic back pain is an actual problem of clinical medicine, the pathogenesis of which includes peripheral nociceptive stimulation, peripheral and/or central inflammation, abnormality of the central pain modulation network and mixed onset of various pathological mechanisms. Sources of nociceptive signal generation include the intervertebral disc, muscles, fasciae, facet joints, sacroiliac joints, pubic symphysis, ligaments and joint capsule, and other structures that contain nociceptors. Any event that causes tissue degeneration activates a massive inflammatory response that infiltrates the MPD, joints, muscles, fascia and other tissues, stimulates nociceptive receptors to produce inflammatory substances, which directly damages the nerve root and causes pain. Simultaneously, the damaged MPD and endplate stimulate pathological and invasive growth and proliferation of vessels and nerves in the MPD. Increasing evidence also suggests that systemic inflammation plays a crucial role in the pathogenesis of chronic back pain. The central mechanism of back pain involves altered sensory processing in the brain. Dysfunction of the descending pain modulation system results in amplification of pain information in the brain. Since monotherapy for chronic back pain is not optimal, it is necessary to promote the comprehensive treatment recommended by current international clinical guidelines and it is reasonable to combine several therapies to improve the clinical effect of therapy. The combination of Tizanidine and Mirtazapine is an effective pharmacotherapy for chronic back pain. KEYWORDS: Chronic back pain, pathogenesis of dorsalgia, Tizanidine, Mirtazapine

Association Between Patient and System Delays and In-Hospital Mortality in Primary PCI for STEMI: Findings from a Large, Nationwide Inpatients Sample

PurposeSystem delay is associated with mortality in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). However, the influence of patient delay has been relatively overlooked. We aimed to evaluate the influence of patient and system delays on STEMI patients undergoing primary PCI in China. MethodsSTEMI patients registered at the Nationwide Chinese Cardiovascular Association Database-Chest Pain Center from January 2017 to September 2021 were screened. The exposures were total ischemic time (TIT), system delay and patient delay. The primary outcome was in-hospital mortality. ResultsAmong 458,260 patients from 2529 centers, median TIT, system delay and patient delay were 4.1, 1.5 and 2.1 hours, respectively. The adjusted odds ratio of in-hospital mortality increased by 2.2% (odds ratio [OR], 1.022, 95% confidence interval [CI], 1.017-1.027), 2.3% (1.023, 1.006-1.040) and 2.2% (1.022, 1.017-1.027) for every one-hour increase in TIT, system delay and patient delay, respectively. ConclusionsPatient delay demonstrated a comparable impact to system delay on in-hospital mortality among STEMI patients undergoing primary PCI. Widespread primary PCI-capable center, improved awareness about myocardial infarction and regional transfer system are essential to shorten patient delay.