Pathophysiology Of Pain Research Articles

Pain in Huntington's disease and its potential mechanisms.

Pain is common and frequent in many neurodegenerative diseases, although it has not received much attention. In Huntington's disease (HD), pain is often ignored and under-researched because attention is more focused on motor and cognitive decline than psychiatric symptoms. In HD progression, pain symptoms are complex and involved in multiple etiologies, particularly mental issues such as apathy, anxiety and irritability. Because of psychiatric issues, HD patients rarely complain of pain, although their bodies show severe pain symptoms, ultimately resulting in insufficient awareness and lack of research. In HD, few studies have focused on pain and pain-related features. A detailed and systemic pain history is crucial to assess and explore pain pathophysiology in HD. This review provides an overview concentrating on pain-related factors in HD, including neuropathology, frequency, features, affecting factors and mechanisms. More attention and studies are still needed in this interesting field in the future.

Pain management in 2023

Pain is a frequent symptom for healthcare professionals in the community and in hospital. Appropriate management of pain begins with a precise and comprehensive assessment, whether acute or chronic. The available therapies are summarized below, so that they can be used as closely as possible to the pathophysiology of pain. Available drug analgesics are reinforced by non-drug interventions, which are increasingly present in the algology care offering. In 2023, the authorities have announced a new ten-year national plan for pain and palliative care. Proof that this public health issue, at the heart of caregivers' concerns, is also a priority for political leaders.

Real World Clinical Utility of Neurophysiological Measurement Utilizing Closed-Loop Spinal Cord Stimulation in a Chronic Pain Population: The ECAP Study Protocol.

Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patient's pain phenotype, unique neurophysiology, and disease severity.

Anatomical and Functional Connectivity of Critical Deep Brain Structures and Their Potential Clinical Application in Brain Stimulation

Subcortical structures, such as the hippocampus, amygdala, and nucleus accumbens (NAcc), play crucial roles in human cognitive, memory, and emotional processing, chronic pain pathophysiology, and are implicated in various psychiatric and neurological diseases. Interventions modulating the activities of these deep brain structures hold promise for improving clinical outcomes. Recently, non-invasive brain stimulation (NIBS) has been applied to modulate brain activity and has demonstrated its potential for treating psychiatric and neurological disorders. However, modulating the above deep brain structures using NIBS may be challenging due to the nature of these stimulations. This study attempts to identify brain surface regions as source targets for NIBS to reach these deep brain structures by integrating functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We used resting-state functional connectivity (rsFC) and probabilistic tractography (PTG) analysis to identify brain surface stimulation targets that are functionally and structurally connected to the hippocampus, amygdala, and NAcc in 119 healthy participants. Our results showed that the medial prefrontal cortex (mPFC) is functionally and anatomically connected to all three subcortical regions, while the precuneus is connected to the hippocampus and amygdala. The mPFC and precuneus, two key hubs of the default mode network (DMN), as well as other cortical areas distributed at the prefrontal cortex and the parietal, temporal, and occipital lobes, were identified as potential locations for NIBS to modulate the function of these deep structures. The findings may provide new insights into the NIBS target selections for treating psychiatric and neurological disorders and chronic pain.

Long-term tactile hypersensitivity after nerve crush injury in mice is characterized by the persistence of intact sensory axons.

Traumatic peripheral nerve injuries are at high risk of neuropathic pain for which novel effective therapies are urgently needed. Preclinical models of neuropathic pain typically involve irreversible ligation and/or nerve transection (neurotmesis). However, translation of findings to the clinic has so far been unsuccessful, raising questions on injury model validity and clinically relevance. Traumatic nerve injuries seen in the clinic commonly result in axonotmesis (ie, crush), yet the neuropathic phenotype of "painful" nerve crush injuries remains poorly understood. We report the neuropathology and sensory symptoms of a focal nerve crush injury using custom-modified hemostats resulting in either complete ("full") or incomplete ("partial") axonotmesis in adult mice. Assays of thermal and mechanically evoked pain-like behavior were paralleled by transmission electron microscopy, immunohistochemistry, and anatomical tracing of the peripheral nerve. In both crush models, motor function was equally affected early after injury; by contrast, partial crush of the nerve resulted in the early return of pinprick sensitivity, followed by a transient thermal and chronic tactile hypersensitivity of the affected hind paw, which was not observed after a full crush injury. The partially crushed nerve was characterized by the sparing of small-diameter myelinated axons and intraepidermal nerve fibers, fewer dorsal root ganglia expressing the injury marker activating transcription factor 3, and lower serum levels of neurofilament light chain. By day 30, axons showed signs of reduced myelin thickness. In summary, the escape of small-diameter axons from Wallerian degeneration is likely a determinant of chronic pain pathophysiology distinct from the general response to complete nerve injury.

Neck pain and headache: Pathophysiology, treatments and future directions

IntroductionNeck pain is a prevalent neurologic and musculoskeletal complaint in the general population and is often associated with primary headache disorders such as migraine and tension-type headache (TTH). A considerable proportion, ranging from 73% to 90%, of people with migraine or TTH also experience neck pain, and there is a positive correlation between headache frequency and neck pain. Furthermore, neck pain has been identified as a risk factor for migraine and TTH. Although the exact underlying mechanisms linking neck pain to migraine and TTH remain uncertain, pain sensitivity appears to play an important role. People with migraine or TTH exhibit lower pressure pain thresholds and higher total tenderness scores compared with healthy controls. PurposeThis position paper aims to provide an overview of the current evidence on the relationship between neck pain and comorbid migraine or TTH. It will encompass the clinical presentation, epidemiology, pathophysiology, and management of neck pain in the context of migraine and TTH. ImplicationsThe relationship between neck pain and comorbid migraine or TTH is incompletely understood. In the absence of robust evidence, the management of neck pain in people with migraine or TTH relies mostly on expert opinion. A multidisciplinary approach is usually preferred, involving pharmacologic and non-pharmacologic strategies. Further research is necessary to fully dissect the linkage between neck pain and comorbid migraine or TTH. This includes the development of validated assessment tools, evaluation of treatment effectiveness, and exploration of genetic, imaging, and biochemical markers that might aid in diagnosis and treatment.

Edukasi Auto Streching pada Kasus Nyeri Leher pada Siswa SMP Nurul Ilmi Kota Jambi

Neck pain is a complaint that often causes a person to come to a health facility for treatment. Auto stretching is a technique of stretching the muscles with the correct direction of pulling which is done independently with the aim of reducing pain. Based on the data collected, it was found that (80%) junior high school students who had less knowledge and had sufficient knowledge 3 (15%). After conducting counseling on reducing neck pain with auto stretching, there was an increase in the knowledge of junior high school students with a percentage of 5% increasing to 90%. The aim of this counseling to the community is to increase the knowledge of junior high school students about auto stretching in cases of neck pain. Methods Implementation of counseling activities is carried out by lecture and demonstration methods with a total of 20 participants. The material presented about auto stretching in neck pain includes the meaning, causes, pathophysiology of neck pain, as well as understanding, benefits, how to implement auto stretching. In counseling, discussions were also held between the presenters and participants to share experiences related to the theme of neck pain. To find out the participants' understanding of the material presented, an evaluation was held by asking a number of questions. The results of this activity showed an increase in junior high school students' knowledge about auto stretching for neck pain

Refractory cancer pain therapy with intrathecal neurolytic technique—a retrospective tertiary care cancer centre experience

Background: The objective of this study is to observe the efficacy of refractory cancer pain therapy with an intrathecal neurolytic technique. Methods: This was a retrospective study of patients who received an intrathecal neurolytic technique between December 2016 and June 2020 at the Department of Anesthesia and Pain Medicine of Shaukat Khanam Memorial Cancer Hospital and Research Center. The data of the patients were retrieved from hospital information system (HIS). Patients were included who had numerical rating score (NRS) ≥8, after monopharmacy or polypharmacy including opioids/neuropathic drugs. Follow-up was conducted by the pain consultant and pain resident post-procedure at 1 week and 4 weeks. Data were documented on a spreadsheet in Microsoft XL and analysed on SPSS version 20. Results: Among 23 patients, numerical rating scale pain score pre-procedure was 8.91 (1.24). It was 3.83 (3.20) and 4.82 (3.41) at 1 and 4 weeks follow-up, respectively. Oral medications were reduced to half of their pre-procedure consumption in 57% of the patients and totally stopped in 30% (n=7) of patients. Complications were reported in 17.4% patients. Hypotension in 13%, and bowel incontinence and leg numbness in 4.3% patients were recorded. Conclusion: This study showed that with appropriate patient selection, understanding of pathophysiology of pain, choice of correct treatment can result in higher success rate. Intrathecal chemical neurolysis can be offered to a subset of patients who have not benefited from other pharmacological therapies.

Ethical and scientific considerations when making decisions to euthanise companion animals

Euthanasia is a highly controversial issue in human society. In the field of veterinary medicine, there are guidelines that are intended to assist with the decision-making around euthanasia and reduce the possible ethical and moral conflicts involved with these situations. In this review, we have collected the existing information that allows veterinarians to better understand the factors surrounding the practice of euthanasia. Specific literature on topics such as the pathophysiology of pain in animals, clinical situations that could lead to a decision to euthanise an animal, possible ethical and moral conflicts, the management of emotions by animal tutors, etc. This article provides a general and practical overview of this potentially complex issue for the benefit of students, veterinarians, and the general public from both an ethical and medical point of view, and covers the fundamental concepts and notions that can facilitate decision-making concerning the euthanasia of animals. Ethical practices in veterinary medicine and the correct application of animal welfare principals are central to making such decisions responsibly.

(030) Reliability of Shear Wave Elastography for the Assessment of Pelvic Floor Muscle Stiffness

Abstract Introduction Shear wave elastography (SWE) has gained popularity for assessing skeletal muscle stiffness and could potentially overcome some limitations associated with the assessment of the pelvic floor muscles (PFMs). Additionally, SWE is a non-invasive and painless alternative to the current method of assessing the PFMs, which is often painful or even impossible to perform in women with sexual pain. Before implementing this promising method, it is of the utmost importance to assess its reliability. Available data are limited and currently, there is no study investigating the reliability of SWE for the assessment of the different PFMs. Objective To investigate the intra-rater and inter-rater reliability of SWE in measuring the stiffness of the different PFMs at rest and during maximal voluntary contraction in asymptomatic women. Methods Thirty asymptomatic nulliparous women participated in the study. They each attended a single assessment session conducted by two independent assessors. SWE assessments were performed using the Aixplorer device (Supersonic Imaging) equipped with linear probes. Four PFMs (i.e., bulbospongiosus, ischiocavernosus, transverse perineal, puborectalis) and the perineal body were assessed at rest and during maximal voluntary contraction. Measurements were taken twice by the first assessor (intra-rater reliability) and once by the second assessor (inter-rater reliability). SWE data were saved and analyzed offline. For both the resting and contraction states, three consecutive frames with stable SWE maps were selected. The average shear modulus was evaluated by manually defining a region of interest that corresponded to the structure assessed. To determine intra- and inter-rater reliability, intraclass correlation coefficients (ICC) were calculated. Results Intra-rater reliability was excellent for the ischiocavernosus and puborectalis at rest and during contraction as well as for the transverse perineal and perineal body during contraction (ICC 0.82-0.95); good for the bulbospongiosus during contraction as well as the transverse perineal and perineal body at rest (ICC 0.61-0.79); and fair for the bulbospongiosus at rest (ICC 0.51). For the inter-rater reliability, the results were as follows: excellent for the transverse perineal and puborectalis during contraction (ICC 0.84-0.89); good for the puborectalis and transverse at rest as well as the perineal body during contraction (ICC 0.62-0.72); fair for the perineal body at rest (ICC 0.48); and poor for the bulbospongiosus and ischiocavernosus muscles (ICC 0.22-0.38) in both states. Conclusions These findings support the intra- and inter-rater reliability of SWE for the assessment of PFM stiffness in women, especially in the puborectalis muscle, transverse perineal muscle, and perineal body. By enabling the assessment of localized areas of stiffness in the different PFMs, SWE may be a stepping stone in enhancing our understanding of the role of the PFMs in the pathophysiology and treatment of sexual pain. Further studies investigating PFM stiffness with the use of SWE assessment are encouraged. Disclosure No

IL-10/β-Endorphin-Mediated Neuroimmune Modulation on Microglia during Antinociception.

Microglia are glial cells centrally related to pathophysiology and neuroimmunological regulation of pain through microglia-neuron crosstalk mechanisms. In contrast, anti-inflammatory mechanisms guided by immunological effectors such as IL-10 trigger the secretion of analgesic substances, culminating in the differential expression of genes encoding endogenous opioid peptides, especially β-endorphin. Thus, when β-endorphin binds to the µ-opioid receptor, it generates neuronal hyperpolarization, inhibiting nociceptive stimuli. This review aimed to summarize the recent advances in understanding the mechanism by which IL-10/β-endorphin can reduce pain. For this, databases were searched for articles from their inception up until November 2022. Two independent reviewers extracted the data and assessed the methodological quality of the included studies, and seventeen studies were considered eligible for this review. Several studies have demonstrated the impact of IL-10/β-endorphin in reducing pain, where IL-10 can stimulate GLP-1R, GRP40, and α7nAChR receptors, as well as intracellular signaling pathways, such as STAT3, resulting in increased β-endorphin expression and secretion. In addition, molecules such as gabapentinoids, thalidomide, cynandione A, morroniside, lemairamin, and cinobufagin, as well as non-pharmacological treatments such as electroacupuncture, reduce pain through IL-10 mediated mechanisms, reflecting a microglia-dependent β-endorphin differential increase. This process represents a cornerstone in pain neuroimmunology knowledge, and the results obtained by different studies about the theme are presented in this review.

The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses.

This review firstly examines the underlying pathophysiology of pain and inflammation associated with orthopedic disease and endotoxemia. Then, it reviews the clinical pharmacology (pharmacokinetics and pharmacodynamics) of both conventional and non-conventional NSAIDs in the adult horse, and finally provides an overview of different modalities to evaluate the therapeutic efficacy of NSAIDs in research.

Tiam1 coordinates synaptic structural and functional plasticity underpinning the pathophysiology of neuropathic pain

Neuropathic pain is a common, debilitating chronic pain condition caused by damage or a disease affecting the somatosensory nervous system. Understanding the pathophysiological mechanisms underlying neuropathic pain is critical for developing new therapeutic strategies to treat chronic pain effectively. Tiam1 is a Rac1 guanine nucleotide exchange factor (GEF) that promotes dendritic and synaptic growth during hippocampal development by inducing actin cytoskeletal remodeling. Here, using multiple neuropathic pain animal models, we show that Tiam1 coordinates synaptic structural and functional plasticity in the spinal dorsal horn via actin cytoskeleton reorganization and synaptic NMDAR stabilization and that these actions are essential for the initiation, transition, and maintenance of neuropathic pain. Furthermore, an antisense oligonucleotides (ASO) targeting spinal Tiam1 persistently alleviate neuropathic pain sensitivity. Our findings suggest that Tiam1-coordinated synaptic functional and structural plasticity underlies the pathophysiology of neuropathic pain and that intervention of Tiam1-mediated maladaptive synaptic plasticity has long-lasting consequences in neuropathic pain management.

Pelvic pain comorbidities associated with quality of life after endometriosis surgery

After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life. This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery. This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank. The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis. Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.

Kynurenine Pathway Metabolites as Potential Biomarkers in Chronic Pain.

Chronic pain is a pressing medical and socioeconomic issue worldwide. It is debilitating for individual patients and places a major burden on society in the forms of direct medical costs and lost work productivity. Various biochemical pathways have been explored to explain the pathophysiology of chronic pain in order to identify biomarkers that can potentially serve as both evaluators of and guides for therapeutic effectiveness. The kynurenine pathway has recently been a source of interest due to its suspected role in the development and sustainment of chronic pain conditions. The kynurenine pathway is the primary pathway responsible for the metabolization of tryptophan and generates nicotinamide adenine dinucleotide (NAD+), in addition to the metabolites kynurenine (KYN), kynurenic acid (KA), and quinolinic acid (QA). Dysregulation of this pathway and changes in the ratios of these metabolites have been associated with numerous neurotoxic and inflammatory states, many of which present simultaneously with chronic pain symptoms. While further studies utilizing biomarkers to elucidate the kynurenine pathway's role in chronic pain are needed, the metabolites and receptors involved in its processes nevertheless present researchers with promising sources of novel and personalized disease-modifying treatments.

Emerging Advances in Nanocarriers Approaches in the Effective Therapy of Pain Related Disorders: Recent Evidence and Futuristic Needs.

Pain disorders are the primary cause of disability nowadays. These disorders, such as rheumatoid arthritis (RA) and osteoarthritis (OA), cause loss of function, joint pain and inflammation and deteriorate the quality of life. The treatment of these inflammatory diseases includes anti-inflammatory drugs administered via intra-articular, topical or oral routes, physical rehabilitation or surgery. Owing to the various side effects these drugs could offer, the novel approaches and nanomaterials have shown potential to manage inflammatory diseases, prolonged half-life of anti-inflammatory drugs, reduced systemic toxicity, provide specific targeting, and refined their bioavailability. This review discusses in brief about the pain pathophysiology and its types. The review summarizes the conventional therapies used to treat pain disorders and the need for novel strategies to overcome the adverse effects of conventional therapies. The review describes the recent advancements in nanotherapeutics for inflammatory diseases using several lipids, polymers and other materials and their excellent efficiency in improving the treatment over conventional therapies. The results of the nanotherapeutic studies inferred that the necessity to use nanocarriers is due to their controlled release, targeting drug delivery to inflamed tissues, low toxicity and biocompatibility. Therefore, it is possible to assert that nanotechnology will emerge as a great tool for advancing the treatment of pain disorders in the near future.

Differences in the elastic modulus of the lumbar muscles between female athletes with and without low back pain

BackgroundLow back pain is the most prevalent musculoskeletal disorder affecting performance and sports participation among athletes and is more prevalent among female athletes. Evaluating the stiffness of the lumbar muscles is important for understanding the pathophysiology of low back pain. Therefore, this study examined the differences in stiffness of the lumbar multifidus and erector spinae muscles between female university athletes with and without low back pain. MethodsThis was a cross-sectional study. The study was conducted at a single centre, the university research laboratory. Twenty female university athletes with low back pain or a history of low back pain and 20 without low back pain participated in this study. The shear elastic moduli of the multifidus and erector spinae muscles were evaluated in the prone (to relax the muscles) and sitting with 35° of trunk flexion (to stretch the muscles) positions using shear wave ultrasound imaging equipment. FindingsThe low back pain group showed significantly greater shear elastic modulus in the multifidus in both prone and sitting positions than the non-low back pain group. There were no differences in the erector spinae muscle between the two groups at either position. InterpretationThese results provide new insights into the microscopic characteristics of low back pain pathophysiology in young female athletes. Stiffness assessment using shear wave elastography will help provide a specific treatment strategy for female athletes with low back pain or a history of low back pain.

PAIN MANAGEMENT IN ENDODONTICS: A DETAILED REVIEW ON CAUSES AND MANAGEMENT OF PAIN IN IRREVERSIBLE PULPITIS AND APICAL PERIODONTITIS

Managing endodontic pain is one of the major challenges faced by dentist in clinical practice. Endodontic pain management consists of a wide range of treatment options ranging from local anesthesia modifications to irrigation and disinfection of the canal depending on the etiology. To find a proper protocol for pain management, through understanding and knowledge of pathophysiology of pain is mandatory. This article reviews the treatment strategies of both irreversible pulpitis and apical periodontitis in detail.

Longitudinal Predictors of Pain in Pediatric Sickle Cell Disease.

Despite the identified pathophysiology of vaso-occlusive pain in sickle cell disease (SCD), predictors of pain in youth with SCD remain elusive. In this study, we measured changes in pain frequency, intensity, and interference over 1 year and examined biopsychosocial risk factors (SCD disease severity, age, female, depression, and sleep quality) as possible longitudinal predictors. Medical history was obtained from retrospective chart review for 79 children with SCD (ages 2-18 years; 48.1% female; 100% Black/African American; 83.5% SCD, SS genotype). As part of a clinical screening protocol, caregivers (n = 79) and youth 8-18 years (n = 43) completed psychosocial questionnaires approximately 1 year apart (M = 15.52 months, SD = 5.69). Zero-order correlations, paired t-tests, and hierarchical linear models examined longitudinal predictors of pain. The longitudinal bidirectional relationship between pain and sleep was also examined. The rate of severe SCD disease increased from 41.8% to 55.7% across the year, while most hematologic medical parameters remained stable. Increased depression and pain interference at survey 1 significantly predicted increased pain interference at survey 2. Poor sleep quality and increased pain frequency at survey 1 predicted increased pain frequency at survey 2. Finally, increased pain interference at survey 1 predicted poor sleep quality at survey 2. History of pain, depression, and sleep quality were longitudinal predictors of pain over 1 year in youth with SCD. Identifying longitudinal predictors of pain may lead to earlier identification of patients with a high-risk SCD pain phenotype and earlier medical, psychological, and behavioral interventions.

Pharmacological Modulation of the MIP-1 Family and Their Receptors Reduces Neuropathic Pain Symptoms and Influences Morphine Analgesia: Evidence from a Mouse Model

Neuropathic pain pathophysiology is not fully understood, but it was recently shown that MIP-1 family members (CCL3, CCL4, and CCL9) have strong pronociceptive properties. Our goal was to examine how pharmacological modulation of these chemokines and their receptors (CCR1 and CCR5) influence hypersensitivity after nerve injury in Albino Swiss male mice. The spinal changes in the mRNA/protein levels of the abovementioned chemokines and their receptors were measured using RT-qPCR and ELISA/Western blot techniques in a mouse model of chronic constriction injury of the sciatic nerve. Behavioral studies were performed using the von Frey and cold plate tests after pharmacological treatment with neutralizing antibodies (nAbs) against chemokines or antagonists (CCR1-J113863, CCR5-TAK-220/AZD-5672) alone and in coadministration with morphine on Day 7, when the hypersensitivity was fully developed. Our results showed enhanced protein levels of CCL3 and CCL9 1 and 7 days after nerve injury. The single intrathecal administration of CCL3 or CCL9 nAb, J113863, TAK-220, or AZD-5672 diminished neuropathic pain symptoms and enhanced morphine analgesia. These findings highlight the important roles of CCL3 and CCL9 in neuropathic pain and additionally indicate that these chemokines play essential roles in opioid analgesia. The obtained results suggest CCR1 and CCR5 as new, interesting targets in neuropathy treatment.