Acute blockage of forearm supination due to flap tear of the triangular fibrocartilage disc: A case report.

RATIONALE: Acute blockage of forearm supination has been reported in several studies. It is caused by loose bodies in the wrist joint, extensor carpi ulnaris tendon interposition, and distal radioulnar joint (DRUJ) injuries, including forearm bone fractures. Some studies have reported cases of DRUJ injuries caused by triangular fibrocartilage complex (TFCC) tears.We report a case of acute blockage of forearm supination after minor trauma and suggest a possible TFCC tear when a patient complains of forearm supination blocking. In addition, we present a comparison between our case and other reports on etiology, magnetic resonance imaging (MRI) findings, and arthroscopic findings, and show the specific characteristics of our case. PATIENTS CONCERNS: A 22-year-old male presented with left wrist pain as the chief complaint. He was injured 2 months prior to pushing his left hand on the floor during exercise. Physical examination showed a relative limitation of range of motion (ROM) in the left wrist of about 10° in flexion and about 15° in extension compared with the right side. The patient also complained of supination limitation and volar side wrist pain during supination. The patient showed tenderness in the axial compression test. DIAGNOSES: Plain radiographs showing no abnormalities. MRI showed a TFCC tear in the central portion. A torn flap of the TFCC was interposed on the volar side of the DRUJ. INTERVENTIONS: Arthroscopic surgery of the left wrist joint was performed. Arthroscopic examination revealed a tear in the TFCC on the radial side. A torn flap was interposed on the volar side of the DRUJ. We removed the flap from the DRUJ using an arthroscopic grasper and partially resected it. OUTCOMES: Intraoperative tests showed no locking and the forearm was well supinated. Two months after the surgery, the patient had no pain and showed full forearm supination. LESSONS: DRUJ blocking due to a TFCC tear should be suspected when acute blockage of forearm supination occurs after minor trauma. MRI is helpful for diagnosis; however, we suggest that the diagnosis should be confirmed through arthroscopy. Symptoms can be resolved by surgical treatment using arthroscopy.

Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity.

Background: Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored. Objectives: To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity. Methods: Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids. Results: The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples. Conclusions: scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.

[Clinical value of focused ultrasound ablation surgery in the treatment of abdominal wall endometriosis].

Objective: To explore the effectiveness and safety of focused ultrasound ablation surgery (FUAS) for abdominal wall endometriosis. Methods: From November 2019 to October 2022, a total of 34 patients with abdominal wall endometriosis who underwent FUAS were collected, and their clinical features, imaging features, intraoperative treatment and side effects after treatment were analyzed retrospectively, and the improvement of symptoms and re-intervention were followed up. Results: (1) Characteristics of clinical data: the average age of 34 patients with abdominal wall endometriosis was (32.8±3.8) years old. The largest diameter of the lesion was 48 mm, and the median lesion diameter was 24 mm. Thirty cases (88%, 30/34) had moderate to severe periodic pain in abdominal incision before FUAS. All patients were diagnosed by preoperative magnetic resonance imaging, including 19 cases (56%, 19/34) of superficial type, 8 cases (24%, 8/34) of intermediate type and 7 cases (21%, 7/34) of deep type. (2) FUAS treatment parameters: ablation was completed with average operation time of (64±18) minutes, average sonication time was (385±108) s, (103±11) W of average power, (38 819±16 309) J of average total energy, the average treatment area volume of (3.11±1.42) cm3, and (377.79±106.34) s/h of average treatment intensity. (3) Efficiency: the pain of patients after FUAS was significantly relieved, and the pain scores of patients after 1 month, 3 months, 6 months and 1 year after FUAS were significantly decreased (Z=-4.66, -5.13, -5.11 and -4.91, all P<0.01). One year after FUAS, the near relief and effective pain relief rate was 74% (25/34), and the clinical effective rate was 85% (29/34). Five patients recurred after one year, including 3 patients who underwent abdominal wall endometriosis lesion resection and 2 patients who received drug treatment. One month after FUAS, the size of the lesion did not change significantly compared with that before FUAS (P>0.05), and the size of the lesion decreased significantly after FUAS at 3 months, 6 months and 1 year (Z=-2.15, -2.67 and -3.41, all P<0.05). It has no difference in pain relief among different types (P>0.05), but has significant difference in focus reduction among three types (P<0.01). (4) Safety: there were 34 cases (100%, 34/34) of skin burning sensation, 19 cases (56%, 19/34) of pain in the treatment area and 2 cases (6%, 2/34) of hematuria. All patients got better after corresponding treatments. Conclusion: FUAS is safe and effective for the treatment of abdominal wall endometriosis, which has clinical application value.

Analysis of clinical changes and magnetic resonance imaging features of 37 patients with temporomandibular joint disc condylar complex with anterior disc displacement without reduction.

OBJECTIVES: This study aims to investigate clinical outcomes, imaging changes, and age differences with regard to temporomandibular joint disc condylar complex with anterior disc displacement without reduction (ADDWoR). METHODS: A total of 37 patients (45 lateral joints) with ADDWoR who were admitted to The First Affiliated Hospital of Zheng Zhou University from January 2016 to June 2023 were selected. The patients were composed of 4 males and 33 females and had an average age of 23.5 years. The average course of the disease was 14.4 months. Clinical and magnetic resonance imaging (MRI) data were collected at the end of initial diagnosis and follow-up, and the length and thickness of the articular disc, the angle of the disc condyle, and the height of the condyle were measured. The statistical significance of the changes was assessed using SPSS 25.0 software package. RESULTS: At the end of follow-up, disc displacement in three patients (three lateral joints) was healed. Approximately 48.4% of the patients felt that limitation of mandibular movement was not alleviated; 58.3% of patients reported that pain during mouth opening was not reduced; 54.5% reported pain while chewing; 33.3% of the patients showed facial deviation, and only one showed remission. The mean disk-condyle angle increased from 61.63° to 67.81°. The average length of articular disc shortened from 8.20 mm to 7.27 mm, and the height of the condyle significantly decreased from 23.17 mm to 22.76 mm (P<0.05). The absorption ratio of the condyle increased, and no significant differences in the changes of joint soft and hard tissues between the adolescent and adult groups (P>0.05). CONCLUSIONS: In different age groups of patients with ADDWoR, clinical symptoms cannot be completely relieved. The disc is anteriorly displaced and shortens, condylar height decreases, and secondary facial asymmetry and mandibular retraction occur.

Neuron-astrocyte metabolic coupling facilitates spinal plasticity and maintenance of inflammatory pain.

Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the central nervous system, but neither its involvement in pathological pain nor in spinal plasticity has been tested. Here we report a form of neuroglia signalling involving spinal astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation of the Protein Targeting to Glycogen (PTG) in spinal astrocytes. PTG drove glycogen build-up in astrocytes, and blunting glycogen accumulation and turnover by Ptg gene deletion reduced pain-related behaviours and promoted faster recovery by shortening pain maintenance in mice. Furthermore, mechanistic analyses revealed that glycogen dynamics is a critically required process for maintenance of pain by facilitating neuronal plasticity in spinal lamina 1 neurons. In summary, our study describes a previously unappreciated mechanism of astrocyte-neuron metabolic communication through glycogen breakdown in the spinal cord that fuels spinal neuron hyperexcitability.

Targeting STAT6-mediated synovial macrophage activation improves pain in experimental knee osteoarthritis.

BACKGROUND: Pain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage. We aimed to identify key mechanisms mediating synovial macrophage activation and test the role of STAT signaling in macrophages on pain outcomes in experimental knee OA. METHODS: We induced experimental knee OA in rats via knee destabilization surgery, and performed RNA sequencing analysis on sorted synovial tissue macrophages to identify macrophage activation mechanisms. Liposomes laden with STAT1 or STAT6 inhibitors, vehicle (control), or clodronate (depletion control) were delivered selectively to synovial macrophages via serial intra-articular injections up to 12 weeks after OA induction. Treatment effects on knee and hindpaw mechanical pain sensitivity were measured during OA development, along with synovitis, cartilage damage, and synovial macrophage infiltration using histopathology and immunofluorescence. Lastly, crosstalk between drug-treated synovial tissue and articular chondrocytes was assessed in co-culture. RESULTS: The majority of pathways identified by transcriptomic analyses in OA synovial macrophages involve STAT signaling. As expected, macrophage depletion reduced pain, but increased synovial tissue fibrosis and vascularization. In contrast, STAT6 inhibition in macrophages led to marked, sustained improvements in mechanical pain sensitivity and synovial inflammation without worsening synovial or cartilage pathology. During co-culture, STAT6 inhibitor-treated synovial tissue had minimal effects on healthy chondrocyte gene expression, whereas STAT1 inhibitor-treated synovium induced changes in numerous cartilage turnover-related genes. CONCLUSION: These results suggest that STAT signaling is a major mediator of synovial macrophage activation in experimental knee OA. STAT6 may be a key mechanism mediating the release of nociceptive factors from macrophages and the development of mechanical pain sensitivity. Whereas therapeutic depletion of macrophages paradoxically increases inflammation and fibrosis, blocking STAT6-mediated synovial macrophage activation may be a novel strategy for OA-pain management without accelerating tissue damage.

Peripheral nerve stimulation for psoas muscle pain.

The psoas muscle is the largest muscle in the lower lumbar spine and is innervated by the ipsilateral lumbar spinal nerve roots (L2-L4). Here, we present a 44-year-old female with left hip pain in the posterolateral aspect of the left hip radiating to the ipsilateral hamstring, and psoas atrophy (based on imaging). She is now reported to have over 50% improvement in pain scores after underdoing temporary peripheral nerve stimulation of the psoas muscle as well as significant improvement in muscle atrophy based on an electromyography (EMG) study. This case study is the first to report documented improvement in muscle atrophy based on EMG after peripheral nerve stimulation of the targeted area.

In this case study, peripheral nerve stimulation (PNS) was used for a patient suffering from pain and decreased size of the psoas muscle. The psoas muscle is responsible for walking, running and getting up from a seated position and is the largest muscle in the lower back. This study showed that peripheral nerve stimulation was effective not only for the relief of muscle pain but also for recovery of the size of the affected muscle.

Viable cartilage allograft outperforms existing treatments for focal knee cartilage defects.

PURPOSE: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. METHOD: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. RESULTS: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). CONCLUSION: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. LEVEL OF EVIDENCE: Level IV study.

Characterising umbilical abdominal wall endometriosis as a distinct subgroup of abdominal wall endometriosis - retrospective cohort study.

Abdominal wall endometriosis (AWE) is one of the rarest forms of endometriosis. Little is known about differences between umbilical AWE (U-AWE) and non-umbilical AWE (non-U-AWE) patients. This retrospective cohort study included patients treated for AWE at tertiary endometriosis centre between 2012 and 2020. Patients were divided into two groups - umbilical AWE and non-umbilical AWE.We identified 14 U-AWE and 45 non-U-AWE patients who mostly had lesions in caesarean section scar (38, 64.4%), rarely at other locations (7, 11.9%). Infertility rates for U-AWE patients and non-U-AWE patients were 57.1% and 17.8%, respectively. Concurrent or previous peritoneal endometriosis was noted in 85.7% of U-AWE and 24.4% of non-U- AWE patients. In addition, U-AWE patients and non-UAWE patients significantly differed in following: parity, number of previous caesarean sections, lesion size, prevalence of concurrent or previous deep infiltrating endometriosis, bleeding from abdominal wall, cyclic pain, continuous pain.Infertility and pelvic endometriosis were more prevalent in U-AWE patients. Our data suggests that U-AWE may be a specific marker for a patient highly prone to pelvic endometriosis and subsequent infertility. Findings suggests that clinician should consider comprehensive evaluation of U-AWE patients.

Evaluation of Anti-Nociceptive, Anti-Inflammatory, and Anti-Fibrotic effects of noscapine against a rat model of Achilles tendinopathy.

During tendinopathy, prolonged inflammation results in fibrosis and the adherence of tendons to the adjacent tissues, causing discomfort and movement disorders. As a natural compound, noscapine has several anti-inflammatory and anti-fibrotic properties. Therefore, we aimed to investigate the effects of noscapine against a rat model of tendinopathy. We created a surgical rat model of Achilles tendon damage to emulate tendinopathy. Briefly, an incision was made on the Achilles tendon, and it was then sutured using an absorbable surgical thread. Immediately, the injured area was topically treated with the vehicle, noscapine (0.2, 0.6, and 1.8 mg/kg), or dexamethasone (0.1 mg/kg) as a positive control. During the 19-day follow-up period, animals were assessed for weight, behavior, pain, and motor coordination testing. On day 20th, the rats were sacrificed, and the tendon tissue was isolated for macroscopic scoring, microscopic (H&E, Masson's trichrome, Ki67, p53) analyses, and cytokine secretion levels. The levels of macroscopic parameters, including thermal hyperalgesia, mechanical and cold allodynia, deterioration of motor coordination, tendon adhesion score, and microscopic indices, namely histological adhesion, vascular prominence and angiogenesis, and Ki67 and p53 levels, as well as fibrotic and inflammatory biomarkers (IL-6, TNF-α, TGF-ß, VEGF) were significantly increased in the vehicle group compared to the sham group (P < 0.05-0.001 for all cases). In contrast, the administration of noscapine (0.2, 0.6, and 1.8 mg/kg) attenuated the pain, fibrosis, and inflammatory indices in a dose-dependent manner compared to the vehicle group (P < 0.05-0.001). Histological research indicated that noscapine 0.6 and 1.8 mg/kg had the most remarkable healing effects. Interestingly, two higher doses of noscapine had impacts similar to those of the positive control group in both clinical and paraclinical assessments. Taken together, our findings suggested that noscapine could be a promising medicine for treating tendinopathies.

Complication Rate after Percutaneous Liver Biopsy Using a Real-time Ultrasound Approach and Introducing a Uniform Methodology: A Brief Report.

Following the initial liver biopsy attempts, several techniques using a wide range of methodologies and materials were developed. Many studies on the evaluation of post-liver biopsy complications were conducted. However, their fundamental limitation was significant variance in patient demographics and methodology, which might account for the inconsistent outcomes. Therefore, a uniform methodology to perform percutaneous liver biopsies that result in comparable outcomes around the world is required. This study aimed to determine the precise complication rate following percutaneous liver biopsy using a consistent method in all individuals. It also aimed to establish a consistent operating procedure for a percutaneous liver biopsy that yielded comparable outcomes. Between July 2018 and July 2019, 116 patients were enrolled in this retrospective study for percutaneous liver biopsy. All individuals underwent a biopsy using the same procedure. There was an attempt to exclude elements that could have an impact on the complication rate. For this purpose, the same type and size of needle were utilized. Moreover, a single needle pass, a subcostal approach, deep inspiration breath holding, identical pre- and post-biopsy preparation, real-time ultrasonography guidance, the use of a single operator, and the absence of sedation or general anesthesia were the other approaches that were used to minimize the impact of variables that could raise complication rates. The overall complication rate was 19.8%, of which 18.9% of patients experienced pain and mild bleeding, and one patient (0.9%) experienced hematoma necessitating precautionary hospitalization. The overall percentage of patients who experienced pain was 13.8%. No further complications were observed. The findings of this study could provide an accurate estimate of the post-liver biopsy complication rate. Furthermore, due to a lower complication rate than other practiced procedures, this uniform methodology could be an attractive alternative in clinical practice. However, more research is required to confirm these results.

Magnetic Resonance Image Findings and Potential Anatomic Risk Factors for Chodromalacia in Children and Adolescents Suffering from Non-Overload Atraumatic Knee Pain in the Ambulant Setting.

PURPOSE: To evaluate magnetic resonance image (MRI) findings in children and adolescents suffering from knee pain without traumatic or physical overload history and to identify potential anatomic risk factors. MATERIAL AND METHODS: A total of 507 MRIs of 6- to 20-year-old patients (251 males; 256 females) were evaluated with regard to detectable pathologies of the knee. The results were compared to a control group without pain (n = 73; 34 males; 39 females). A binary logistic regression model and t-tests for paired and unpaired samples were used to identify possible risk factors and significant anatomic differences of the study population. RESULTS: In 348 patients (68.6%), at least one pathology was detected. The most commonly detected finding was chondromalacia of the patellofemoral (PF) joint (n = 205; 40.4%). Chondral lesions of the PF joint occurred significantly more often in knee pain patients than in the control group (40% vs. 11.0%; p = 0.001), especially in cases of a patella tilt angle > 5° (p ≤ 0.001), a bony sulcus angle > 150° (p = 0.002), a cartilaginous sulcus angle > 150° (p = 0.012), a lateral trochlear inclination < 11° (p ≤ 0.001), a lateralised patella (p = 0.023) and a Wiberg type II or III patella shape (p = 0.019). Moreover, a larger patella tilt angle (p = 0.021), a greater bony sulcus angle (p = 0.042), a larger cartilaginous sulcus angle (p = 0.038) and a lower value of the lateral trochlear inclination (p = 0.014) were detected in knee pain patients compared to the reference group. CONCLUSION: Chondromalacia of the PF joint is frequently observed in children and adolescents suffering from non-overload atraumatic knee pain, whereby a patella tilt angle > 5°, a bony sulcus angle > 150°, a cartilaginous sulcus angle > 150°, a lateral trochlear inclination < 11°, a lateralised patella and a Wiberg type II or III patella shape seem to represent anatomic risk factors.

Brain alterations in regions associated with end-organ diabetic microvascular disease in diabetes mellitus: A UK Biobank study.

BACKGROUND: Diabetes mellitus (DM) is associated with structural grey matter alterations in the brain, including changes in the somatosensory and pain processing regions seen in association with diabetic peripheral neuropathy. In this case-controlled biobank study, we aimed to ascertain differences in grey and white matter anatomy in people with DM compared with non-diabetic controls (NDC). METHODS: This study utilises the UK Biobank prospective, population-based, multicentre study of UK residents. Participants with diabetes and age/gender-matched controls without diabetes were selected in a three-to-one ratio. We excluded people with underlying neurological/neurodegenerative disease. Whole brain, cortical, and subcortical volumes (188 regions) were compared between participants with diabetes against NDC corrected for age, sex, and intracranial volume using univariate regression models, with adjustment for multiple comparisons. Diffusion tensor imaging analysis of fractional anisotropy (FA) was performed along the length of 50 white matter tracts. RESULTS: We included 2404 eligible participants who underwent brain magnetic resonance imaging (NDC, n = 1803 and DM, n = 601). Participants with DM had a mean (±standard deviation) diagnostic duration of 18 ± 11 years, with adequate glycaemic control (HbA1C 52 ± 13 mmol/mol), low prevalence of microvascular complications (diabetic retinopathy prevalence, 5.8%), comparable cognitive function to controls but greater self-reported pain. Univariate volumetric analyses revealed significant reductions in grey matter volume (whole brain, total, and subcortical grey matter), with mean percentage differences ranging from 2.2% to 7% in people with DM relative to NDC (all p < 0.0002). The subcortical (bilateral cerebellar cortex, brainstem, thalamus, central corpus callosum, putamen, and pallidum) and cortical regions linked to sensorimotor (bilateral superior frontal, middle frontal, precentral, and postcentral gyri) and visual functions (bilateral middle and superior occipital gyri), all had lower grey matter volumes in people with DM relative to NDC. People with DM had significantly reduced FA along the length of the thalamocortical radiations, thalamostriatal projections, and commissural fibres of the corpus callosum (all; p < 0·001). INTERPRETATION: This analysis suggests that anatomic differences in brain regions are present in a cohort with adequately controlled glycaemia without prevalent microvascular disease when compared with volunteers without diabetes. We hypothesise that these differences may predate overt end-organ damage and complications such as diabetic neuropathy and retinopathy. Central nervous system alterations/neuroplasticity may occur early in the natural history of microvascular complications; therefore, brain imaging should be considered in future mechanistic and interventional studies of DM.

Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution.

Microglia are implicated as primarily detrimental in pain models; however, they exist across a continuum of states that contribute to homeostasis or pathology depending on timing and context. To clarify the specific contribution of microglia to pain progression, we take advantage of a temporally controlled transgenic approach to transiently deplete microglia. Unexpectedly, we observe complete resolution of pain coinciding with microglial repopulation rather than depletion. We find that repopulated mouse spinal cord microglia are morphologically distinct from control microglia and exhibit a unique transcriptome. Repopulated microglia from males and females express overlapping networks of genes related to phagocytosis and response to stress. We intersect the identified mouse genes with a single-nuclei microglial dataset from human spinal cord to identify human-relevant genes that may ultimately promote pain resolution after injury. This work presents a comprehensive approach to gene discovery in pain and provides datasets for the development of future microglial-targeted therapeutics.

Epidural administration of large dose of opioid µ receptor agonist may impair cardiac functions and myocardial viability via desensitizing transient receptor potential vanilloid 1.

The incidence of postoperative myocardial injury remains high as the underlying pathogenesis is still unknown. The dorsal root ganglion (DRG) neurons express transient receptor potential vanilloid 1 (TRPV1) and its downstream effector, calcitonin gene-related peptide (CGRP) participating in transmitting pain signals and cardiac protection. Opioids remain a mainstay therapeutic option for moderate-to-severe pain relief clinically, as a critical component of multimodal postoperative analgesia via intravenous and epidural delivery. Evidence indicates the interaction of opioids and TRPV1 activities in DRG neurons. Here, we verify the potential impairment of myocardial viability by epidural usage of opioids in postoperative analgesia. We found that large dose of epidural morphine (50 µg) significantly worsened the cardiac performance (+dP/dtmax reduction by 11% and -dP/dtmax elevation by 24%, all P < 0.001), the myocardial infarct size (morphine vs Control, 0.54 ± 0.09 IS/AAR vs. 0.23 ± 0.06 IS/AAR, P < 0.001) and reduced CGRP in the myocardium (morphine vs. Control, 9.34 ± 2.24 pg/mg vs. 21.23 ± 4.32 pg/mg, P < 0.001), while induced definite suppression of nociception in the postoperative animals. It was demonstrated that activation of µ-opioid receptor (µ-OPR) induced desensitization of TRPV1 by attenuating phosphorylation of the channel in the dorsal root ganglion neurons, via inhibiting the accumulation of cAMP. CGRP may attenuated the buildup of ROS and the reduction of mitochondrial membrane potential in cardiomyocytes induced by hypoxia/reoxygenation. The findings of this study indicate that epidurally giving large dose of µ-OPR agonist may aggravate myocardial injury by inhibiting the activity of TRPV1/CGRP pathway.

Molecular pathogenesis of OA pain: Past, present, and future.

OBJECTIVE: To provide a historical perspective and narrative review on research into the molecular pathogenesis of osteoarthritis pain. DESIGN: PubMed databases were searched for combinations of "osteoarthritis", "pain" and "animal models" for papers that represented key phases in the history of osteoarthritis pain discovery research including epidemiology, pathology, imaging, preclinical modeling and clinical trials. RESULTS: The possible anatomical sources of osteoarthritis pain were identified over 50 years ago, but relatively slow progress has been made in understanding the apparent disconnect between structural changes captured by radiography and symptom severity. Translationally relevant animal models of osteoarthritis have aided in our understanding of the structural and molecular drivers of osteoarthritis pain, including molecules such as nerve growth factor and C-C motif chemokine ligand 2. Events leading to persistent osteoarthritis pain appear to involve a two-step process involving changes in joint innervation, including neo-innervation of the articular cartilage, as well as sensitization at the level of the joint, dorsal root ganglion and central nervous system. CONCLUSIONS: There remains a great need for the development of treatments to reduce osteoarthritis pain in patients. Harnessing all that we have learned over the past several decades is helping us to appreciate the important interaction between structural disease and pain, and this is likely to facilitate development of new disease modifying therapies in the future.

Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome.

BACKGROUND: Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. METHODS: We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. RESULTS: Intraepidermal Schwann cells were detected in human skin of the finger-but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other-but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. CONCLUSIONS: Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.

Beyond Anatomy: Fat-Suppressed MR and Molecular Imaging of Spinal Pain Generators.

Spine pain is highly prevalent and costly, but evaluation with clinical features and anatomic imaging remain limited. Fat-suppressed MR imaging and molecular imaging (MI) may help identify inflammatory, lesional, and malignant causes. Numerous MI agents are available, each with advantages and disadvantages. Herein, FDG PET, prostate-specific membrane antigen (PSMA), bone radiotracers, and others are highlighted. No specific pain MI agents have been identified, but mechanisms of key agents are shown in video format, and the mechanism of PSMA as a theranostic agent is displayed. A multidisciplinary approach is needed to master this topic.

Surgical versus nonsurgical management of lumbar degenerative spondylolisthesis based on spinal canal cross-sectional area.

Disability and pain associated with lumbar degenerative spondylolisthesis (LDS) result in a significant burden on both the healthcare costs and patients' quality of life. Currently, there exists controversy regarding employment of either nonsurgical management (NSM) or surgical management (SM) in a clinical setting. Spinal canal cross-sectional area (SCA) has been an important morphological parameter for the analysis of LDS. However, there is lack of research about the comparative value of NSM and SM according to SCA. Moreover, previous research have not yet evaluated the clinical most suitable cutoff values of SCA. The objective of this research was to evaluate the effective of NSM and SM for LDS using SCA as an objective morphological parameter. The axial T2 magnetic resonance imaging images were obtained from each patient. We collected SCA samples from 149 patients with LDS. 72 patients underwent SM and the rest did NSM. We measured SCA at the L4/5 LDS on magnetic resonance imaging using a picture archiving and communications system. We measured SCA at the intervertebral disk posterior border, turning down to reach the facet joint side on the opposite edge at the L4/5 level. The average SCA value was 114.34 ±â€…48.11 mm2 in the NSM group and 69.88 ±â€…27.87 mm2 in the SM group. Therefore, the SM group had considerably lower SCA (P < .001). In view of the effectiveness of SCA as a prediction factor of surgical option, Receiver Operating Characteristic curve analysis show the optimal cutoff value for SCA as 83.21 mm2, with 70.8% sensitivity, 71.4% specificity, and an area under the curve of 0.80 (95% CI, 0.73-0.87). The narrower the SCA, the higher the probability of SM. Thus, it is proposed that to evaluate surgical decision making, the pain physician should carefully inspect the SCA.