Peripheral Tissue Injury Research Articles

Changes in Cx43 and AQP4 Proteins, and the Capture of 3 kDa Dextran in Subpial Astrocytes of the Rat Medial Prefrontal Cortex after Both Sham Surgery and Sciatic Nerve Injury.

A subpopulation of astrocytes on the brain's surface, known as subpial astrocytes, constitutes the "glia limitans superficialis" (GLS), which is an interface between the brain parenchyma and the cerebrospinal fluid (CSF) in the subpial space. Changes in connexin-43 (Cx43) and aquaporin-4 (AQP4) proteins in subpial astrocytes were examined in the medial prefrontal cortex at postoperative day 1, 3, 7, 14, and 21 after sham operation and sciatic nerve compression (SNC). In addition, we tested the altered uptake of TRITC-conjugated 3 kDa dextran by reactive subpial astrocytes. Cellular immunofluorescence (IF) detection and image analysis were used to examine changes in Cx43 and AQP4 protein levels, as well as TRITC-conjugated 3 kDa dextran, in subpial astrocytes. The intensity of Cx43-IF was significantly increased, but AQP4-IF decreased in subpial astrocytes of sham- and SNC-operated rats during all survival periods compared to naïve controls. Similarly, the uptake of 3 kDa dextran in the GLS was reduced following both sham and SNC operations. The results suggest that both sciatic nerve injury and peripheral tissue injury alone can induce changes in subpial astrocytes related to the spread of their reactivity across the cortical surface mediated by increased amounts of gap junctions. At the same time, water transport and solute uptake were impaired in subpial astrocytes.

Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

Chronic pain is a heavily debilitating condition and a huge socio-economic burden, with no efficient treatment. Over the past decade, the gut microbiota has emerged as an important regulator of nervous system’s health and disease states. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Here, we report that male but not female mice lacking Myosin1a (KO) raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic pain in response to a peripheral tissue injury. We further underscore the potential of MYO1A loss-of-function to alter the composition of the gut microbiota and uncover a functional connection between the vulnerability to chronic pain and the dysbiotic gut microbiota of KO-SGH males. As such, parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced pain chronicity in male KO-SGH offspring. Furthermore, in KO-SGH males, this dysbiosis is accompanied by a transcriptomic activation signature in the dorsal root ganglia (DRG) macrophage compartment, in response to tissue injury. We identify CD206+CD163- and CD206+CD163+ as the main subsets of DRG resident macrophages and show that both are long-lived and self-maintained and exhibit the capacity to monitor the vasculature. Consistently, in vivo depletion of DRG macrophages rescues KO-SGH males from injury-induced chronic pain underscoring a deleterious role for DRG macrophages in a Myo1a-loss-of function context. Together, our findings reveal gene-sex-microbiota interactions in determining the predisposition to injury-induced chronic pain and point-out DRG macrophages as potential effector cells.

The Complexity of Neuropathic Pain and Central Sensitization: Exploring Mechanisms and Therapeutic Prospects.

Neuropathic pain is a common pain syndrome, which seriously affects the quality of life of patients. The mechanism of neuropathic pain is complex. Peripheral tissue injury can trigger peripheral sensitization; however, what really plays a key role is the sensitization of the central nervous system. Central sensitization is a key factor in the perception of chronic pain. Central sensitization refers to the increased sensitivity of the central nervous system to pain treatment, which is related to the change of the functional connection mode of the neural network. The current study aims to reveal the basic molecular mechanisms of central sensitization, including the involvement of P2 purine X4 receptor and brain-derived neurotrophic factor. In terms of treatment, although there are drugs and physical therapy, the accuracy of targeting is limited and the efficacy needs to be further improved. Future therapeutic strategies may involve the development of new drugs designed to specifically inhibit the central sensitization process. This article focuses on the effector molecules involved in central sensitization, aiming to elucidate the pathogenesis of neuropathic pain and provide a basis for the development of more effective treatment models.

Impact of Different Flushing Frequencies on Peripheral Intravenous Catheter Failure, Coagulation, and Tissue Injury—A Counterbalanced Preclinical Human Trial

Highlights Abstract Background: Peripheral intravenous venous catheters (PIVCs) are associated with a postinsertion failure incidence of 40%, yet the common maintenance and preventive strategy of saline flushing is poorly understood at a physiological level. Methods: We developed a human model of bilateral cephalic vein cannulation to study the impact of varied PIVC flushing frequency (high frequency, HF; low frequency, LF) over 5 hours on catheter failure (primary outcome), coagulation, platelet aggregation, and local tissue injury. Ultrasound was used in a subset to assess vascular diameter/catheter to vein, blood flow velocity, and thrombus formation. Results: Out of 34 catheters in 17 adult participants, 1/17 (6%) LF catheters failed, which was not significantly different from HF catheters (0/17). Platelet function, activated partial thromboplastin time, and tissue factor were also not different (P > 0.05). However, prothrombin time (PT) increased with HF versus LF after 5 hours (P < 0.05). Ultrasound demonstrated luminal thromboses in veins experiencing both HF (6/7) versus LF (5/7) conditions after 5 hours with nonsignificant changes in vascular diameter and blood flow velocity over time. Conclusions: Although no difference in PIVC failure was observed between HF and LF flushing conditions over 5 hours, greater flushing frequency increased PT time, suggesting delayed activation or consumption of extrinsic coagulation factors. This study also demonstrated feasibility in assessment of luminal thromboses, which were remarkably prevalent after PIVC placement, and changes in vascular diameter and blood flow. This manuscript illustrates that the development of a sensitive human model will be of great use for exploring the impact of interventions on reducing PIVC failure in the future.

Effect of Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain

Chronic back pain (CBP) is a leading cause of disability, and treatment is often ineffective. Approximately 85% of cases are primary CBP, for which peripheral etiology cannot be identified, and maintenance factors include fear, avoidance, and beliefs that pain indicates injury. To test whether a psychological treatment (pain reprocessing therapy [PRT]) aiming to shift patients' beliefs about the causes and threat value of pain provides substantial and durable pain relief from primary CBP and to investigate treatment mechanisms. This randomized clinical trial with longitudinal functional magnetic resonance imaging (fMRI) and 1-year follow-up assessment was conducted in a university research setting from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Clinical and fMRI data were analyzed from January 2019 to August 2020. The study compared PRT with an open-label placebo treatment and with usual care in a community sample. Participants randomized to PRT participated in 1 telehealth session with a physician and 8 psychological treatment sessions over 4 weeks. Treatment aimed to help patients reconceptualize their pain as due to nondangerous brain activity rather than peripheral tissue injury, using a combination of cognitive, somatic, and exposure-based techniques. Participants randomized to placebo received an open-label subcutaneous saline injection in the back; participants randomized to usual care continued their routine, ongoing care. One-week mean back pain intensity score (0 to 10) at posttreatment, pain beliefs, and fMRI measures of evoked pain and resting connectivity. At baseline, 151 adults (54% female; mean [SD] age, 41.1 [15.6] years) reported mean (SD) pain of low to moderate severity (mean [SD] pain intensity, 4.10 [1.26] of 10; mean [SD] disability, 23.34 [10.12] of 100) and mean (SD) pain duration of 10.0 (8.9) years. Large group differences in pain were observed at posttreatment, with a mean (SD) pain score of 1.18 (1.24) in the PRT group, 2.84 (1.64) in the placebo group, and 3.13 (1.45) in the usual care group. Hedges g was -1.14 for PRT vs placebo and -1.74 for PRT vs usual care (P < .001). Of 151 total participants, 33 of 50 participants (66%) randomized to PRT were pain-free or nearly pain-free at posttreatment (reporting a pain intensity score of 0 or 1 of 10), compared with 10 of 51 participants (20%) randomized to placebo and 5 of 50 participants (10%) randomized to usual care. Treatment effects were maintained at 1-year follow-up, with a mean (SD) pain score of 1.51 (1.59) in the PRT group, 2.79 (1.78) in the placebo group, and 3.00 (1.77) in the usual care group. Hedges g was -0.70 for PRT vs placebo (P = .001) and -1.05 for PRT vs usual care (P < .001) at 1-year follow-up. Longitudinal fMRI showed (1) reduced responses to evoked back pain in the anterior midcingulate and the anterior prefrontal cortex for PRT vs placebo; (2) reduced responses in the anterior insula for PRT vs usual care; (3) increased resting connectivity from the anterior prefrontal cortex and the anterior insula to the primary somatosensory cortex for PRT vs both control groups; and (4) increased connectivity from the anterior midcingulate to the precuneus for PRT vs usual care. Psychological treatment centered on changing patients' beliefs about the causes and threat value of pain may provide substantial and durable pain relief for people with CBP. ClinicalTrials.gov Identifier: NCT03294148.

Use of Topical Nitroglycerine in the Neonatal Population Following Peripheral Tissue Ischaemia: Case Report and Updates about Safety Concerns

Neonatal thrombosis is a well-described morbidity occurring in the neonatal intensive care unit. Critically ill neonates are most vulnerable to developing thrombosis with serious complications. Fingers and toes ischaemia secondary to vascular occlusion following central lines insertion remains an uncommon occurrence. The therapeutic approach for peripheral tissue injury using local warming, anticoagulants, thrombolytics or topical hyaluronidase showed limited benefits and potential side effects. Here we report an unusual case of finger ischaemia treated successfully using topical nitroglycerine. This complements previous reports confirming the efficacy and safety of this drug and highlighting its potential benefit in neonates.

Pain management and bupivacaine

Background: Pain is an unpleasant experience associated with tissue damage. Peripheral tissue injury results in functional disturbances in the nervous system. Modern anaesthesiologists are not only concerned about preoperative and intraoperative care of the patient but also with postoperative welfare of the patient.Methods: In present study we have compared the efficacy of injection bupivacaine 0.25% infiltration preoperatively versus postoperatively on duration of postoperative analgesia, VAS (visual analogue scale) at the onset of pain, total analgesia requirement in 24 hours. 150 patients belonging to ASA (American society of anesthesiologists) class I and II between the age of 15 and 75 who underwent lower abdominal surgeries belonging to either sex were included in the study. The patients were randomly allocated to three groups. Control group (C) received 20 ml normal saline, preoperative group (A) received 0.25% bupivacaine before incision, postoperative group (B) received 0.25% bupivacaine before closure.Results: Duration of analgesia, VAS score at the time of first request of analgesia and total doses of analgesia over 24 hours were recorded. The total analgesia requirement was reduced over 24 hours in the group B in which the infiltration was done postoperatively.Conclusions: The postoperative infiltration with 0.25% bupivacaine produces longer duration and better quality of analgesia as compared to preoperative infiltration.

Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury

Systemic lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). We examined whether patrolling HSPCs differ from bone-marrow HSPCs both in SLE and healthy individuals, and how they participate in peripheral tissue injury. By employing next-generation RNA sequencing, the transcriptomes of CD34+ HSPCs deriving from the bone marrow and those patrolling the bloodstream of both healthy and individuals with SLE were compared. Patrolling SLE and Healthy human HSPC kinetics were examined through their inoculation into humanised mice. Patrolling and bone-marrow HSPCs have distinct molecular signatures, while patrolling SLE HSPCs showed an enhanced extramedullary gene expression profile. Non-mobilised, SLE-derived circulating HSPCs demonstrated altered homing capacities. Xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. Circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Patrolling SLE CD34+ HSPCs are able to home at extramedullary sites such as the spleen and kidneys, potentially participating in peripheral tissue injury.

Role of Neuroimmune Crosstalk in Mediating the Anti-inflammatory and Analgesic Effects of Acupuncture on Inflammatory Pain.

Inflammatory pain is caused by peripheral tissue injury and inflammation. Inflammation leads to peripheral sensitization, which may further cause central sensitization, resulting in chronic pain and progressive functional disability. Neuroimmune crosstalk plays an essential role in the development and maintenance of inflammatory pain. Studies in recent years have shown that acupuncture can exert anti-inflammatory and analgesic effects by regulating peripheral (i.e., involving local acupoints and inflamed regions) and central neuroimmune interactions. At the local acupoints, acupuncture can activate the TRPV1 and TRPV2 channels of mast cells, thereby promoting degranulation and the release of histamine, adenosine, and other immune mediators, which interact with receptors on nerve endings and initiate neuroimmune regulation. At sites of inflammation, acupuncture enables the recruitment of immune cells, causing the release of opioid peptides, while also exerting direct analgesic effects via nerve endings. Furthermore, acupuncture promotes the balance of immune cells and regulates the release of inflammatory factors, thereby reducing the stimulation of nociceptive receptors in peripheral organs. Acupuncture also alleviates peripheral neurogenic inflammation by inhibiting the release of substance P (SP) and calcitonin gene-related peptide from the dorsal root ganglia. At the central nervous system level, acupuncture inhibits the crosstalk between glial cells and neurons by inhibiting the p38 MAPK, ERK, and JNK signaling pathways and regulating the release of inflammatory mediators. It also reduces the excitability of the pain pathway by reducing the release of excitatory neurotransmitters and promoting the release of inhibitory neurotransmitters from neurons and glial cells. In conclusion, the regulation of neuroimmune crosstalk at the peripheral and central levels mediates the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain in an integrated manner. These findings provide novel insights enabling the clinical application of acupuncture in the treatment of inflammatory diseases.

Systematic review and meta-analysis: surgical reparative treatment for orthopedic patients with ankle fracture complicated by peripheral tissue injury.

This study aimed to apply meta-analysis to study the efficacy of surgical repair treatment on ankle fractures. The Boolean logic search method was adopted to retrieve relevant randomized control trials (RCTs), with "Fracture", "Ankles", "Fractured Foot", "Fractures Merge", and "Surgical Treatment" as search terms. The databases PubMed, Medline, HowNet, and others were searched from the time of their establishment. The software Review Manager (Rev Man 5.3) was used for meta-analysis. A total of 10 references were included in the study, and most of them had low-risk bias (medium-high quality). The results of meta-analysis showed that after surgical repair treatment, gait was good, while the gait score of the non-surgical group was poor. The result was Chi2 (Chi-squared Test) =57.91, df (degree of freedom) =5, I2=91%, P<0.1, mean difference (MD) =-9.21, 95% CI: -10.25 to -8.17, Z=17.36, P<0.05. The non-surgical group showed a higher degree of pain and poorer ankle and hindfoot functions vs. the surgical group. Also, the pain degree of the non-surgical repair combined with surrounding tissue group was higher, and the ankle and hindfoot functions were poorer vs. the surgical repair treatment group. The Pain intensity results of the surgical and non-surgical groups were Chi2 =12.89, df =2, I2=84%, P<0.1, MD =-9.51, 95% CI: -10.47 to -8.55, Z=19.39, P<0.05; the AOFAS scores of surgical repair treatment and non-surgical repair treatment were Chi2 =27.07, df =6, I2=78%, P<0.1, MD =8.89, 95% CI: 8.26 to 9.71, Z=24.30, P<0.05. It was revealed that surgical repair treatment can significantly reduce the postoperative pain of patients with ankle joint fractures, while the non-surgical repair treatment group had a higher degree of postoperative pain. The result was (MD =2.32, 95% CI: 2.16 to 2.48, I2=100%, Z=28.33, P<0.05). Surgical repair treatment of ankle fracture demonstrated significant curative effects, with fewer adverse reactions, and the stability of the ankle joint was well restored.

Patrolling Human SLE Haematopoietic Progenitors Demonstrate Enhanced Extramedullary Colonisation; Implications for Peripheral Tissue Injury

Systemic Lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). By employing next-generation sequencing, we compared the gene transcription signatures of CD34+ HSPCs deriving from either the bone marrow or HSPCs patrolling the bloodstream of healthy and individuals with SLE, seeking common transcriptional pathways that may have been modified between steady and disease states. Our findings indicate that circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Non-mobilised, SLE-derived circulating HSPCs demonstrated enhanced engrafting and altered differentiation capacities. Importantly, xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. SLE CD34+ HSPCs homing and engraftment at extramedullary sites such as the spleen and kidneys may participate in peripheral tissue injury. Funding Information: This study was supported by the H2020-ERC-2016-ADG-LUPUSCARE-742390 and Greek State Scholarships Foundation (ΙΚΥ) MIS-5000432 and MIS-5001552 grants. Declaration of Interests: None. Ethics Approval Statement: Informed consent was obtained from all patients and human controls prior to sample collection (IRB protocol number 10/22-6-2017). All mouse animal work has been approved by the BRFAA ethics committee and the Attica Veterinary Department (758634/22-11/2019).

Cottonseed Oil Alleviates Ischemic Stroke-Induced Oxidative Stress Injury Via Activating the Nrf2 Signaling Pathway.

Oxidative stress is believed to be one of the primary causes in ischemic stroke injury, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is the most important endogenous antioxidative stress damage pathway. Cottonseed oil (CSO), which is used mostly as a solvent for lipid-soluble drugs, has been shown to exert antioxidative effects against peripheral tissue injury. However, the effects and mechanisms of CSO on ischemic stroke-induced oxidative stress injury and the Nrf2 signaling pathway remain largely unknown. In this study, we investigated the potential of CSO in regulating oxidative stress injury induced by middle cerebral artery occlusion and reperfusion (MCAO-R), or oxygen and glucose deprivation and reperfusion (OGD-R). We found that 1.3mL/kg CSO treatment of male rats with a subcutaneous injection once every other day for 3weeks significantly improved neurological deficit; reduced infarction volume; alleviated neuronal injuries; reduced the content of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and markedly increased the expression of Nrf2. Furthermore, treatment with 10-9μL/mL CSO to a neuron cell line (HT-22) for 24h significantly increased cell viability and decreased cell apoptosis after OGD-R injury; significantly reduced the levels of ROS and MDA; increased the activity of SOD, GSH, and GSH-PX; and induced an increase in Nrf2 nuclear translocation. Based on our findings, we conclude that CSO treatment alleviates ischemic stroke injury-induced oxidative stress via activating the Nrf2 signaling pathway, highlighting the potential that CSO has as a therapeutic for ischemic strokes.

Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte

BackgroundIschemic stroke is the second leading cause of death globally. The narrow time window for administering effective thrombolytic therapy motivates the search for alternative prevention strategies. Microglia and astrocyte activation-mediated inflammation play a pivotal role in ischemic stroke injury. Cottonseed oil (CSO) has been shown to exert anti-inflammatory effects against peripheral tissue injury, although CSO is mostly used as a solvent for lipid-soluble drugs. However, the role of CSO in neuroprotection against stroke has not been previously reported.MethodsWe treated adult male rats with CSO (1.3 ml/kg, subcutaneous injection, once every other day for 3 weeks) and then constructed a middle cerebral artery occlusion (MCAO) model followed by 24 h of reperfusion. Then, we measured the neurological scores, infarction volume, neuronal injury, and brain edema; we also measured the levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), degree of microglial and astrocytic activation, protein expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), C3d and S100A10, and the presence of A1 type astrocytes and A2 type astrocytes.ResultsWe found that CSO treatment significantly improved the neurological deficit, reduced infarction volume, and alleviated neuronal injuries, blood–brain barrier (BBB) disruption, and brain edema. Additionally, CSO treatment significantly reduced microglial and astrocytic activation, inhibited TLR4 and NF-κB protein expression, and reduced the release of IL-1β, IL-6, and TNF-α. Finally, CSO treatment significantly decreased the number of C3d/glial fibrillary acidic protein (GFAP)-positive cells and C3d protein expression, and increased the number of S100A10/GFAP-positive cells and S100A10 protein expression.ConclusionOur results first found that CSO treatment alleviated ischemic stroke injury by reducing microglial and astrocytic activation and inflammation, which was related to the inhibition of TLR4/NF-κB pathway and the reduction of A1 phenotype neurotoxic astrocyte activation, suggesting that CSO could be a new strategy in the prevention of ischemic stroke.

Ketogenic Diet Potentiates Electrical Stimulation-Induced Peripheral Nerve Regeneration after Sciatic Nerve Crush Injury in Rats.

Recent findings indicate that the ketogenic diet (KD) is neuroprotective and electrical stimulation (ES) can improve functional recovery from peripheral nerve injury. However, it is not clear whether KD and ES play a synergistical role in the peripheral nerve recovery following injury. A KD consisting of a 3:1 ratio of fat to carbohydrate+protein is used and is coupled with ES treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery is evaluated by electromyography, and axonal regeneration and myelination by histological methods. The effects on insulin-like growth factor 1 (IGF-1) and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury, are also investigated. The combination of KD and ES synergistically increases muscle force in biceps femoris and gluteus maximus and prevents development of hypersensitivity in biceps femoris. It promotes peripheral nerve regeneration by increasing total axons, axon density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects are due to modulation of the IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. The results establish that KD and ES promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach.

Laparoscopic partial splenectomy of benign tumors assisted by microwave ablation.

The aim of this study is to investigate the application and the feasibility of microwave ablation in laparoscopic partial splenectomy. From January 2018 to June 2019, four patients with benign spleen lesions in our hospital underwent laparoscopic partial splenectomy assisted by microwave ablation. The reviewed parameters included the operation time, intraoperative blood loss, ablation time, frequency of ablation, postoperative drainage time, postoperative hospitalization time, and postoperative complications. All four patients underwent laparoscopic partial splenectomy assisted by microwave ablation successfully, and there were no cases of conversion to laparotomy. The operation time was 100-200 min (mean, 152.5 min) and ablation time was 16-35 min (mean, 22.8 min). The frequency of ablation was 4-7 times (mean, 5.3 times), and the intraoperative blood loss was 5-300 ml (mean, 138.8 ml). The postoperative drainage time was 3-5 d (mean, 3.3 d), and postoperative hospital stay was 3-9 d (mean, 7.8 d). There were no complications such as peripheral tissue injury, massive bleeding, infestation of spleen fossa, and pancreatic leakage. Microwave ablation is worthy of clinical application in laparoscopic partial spleen resection as it is safe and effective with low rates of bleeding and fast recovery.

Effect of anterior cervical discectomy and decompression with different fusion segments on sagittal spine-pelvis balance

To explore the effect on sagittal spine-pelvis balance of different fusion segments in anterior cervical discectomy and fusion (ACDF). The clinical data of 326 patients with cervical spondylotic myelopathy, treated by ACDF between January 2010 and December 2016, was retrospectively analysed. There were 175 males and 151 females with an average age of 56 years (range, 34-81 years). Fusion segments included single segment in 69 cases, double segments in 85 cases, three segments in 90 cases, and four segments in 82 cases. Full spine anterolateral X-ray films were performed before operationand at 12 months after operation. The spine-pelvis parameters of fusion segments were measured and compared. The parameters included C 0-2 Cobb angle, C 2-7 Cobb angle, C 2-7 sagittal vertical axis (C 2-7 SVA), T 1 slope (T 1S), thoracic inlet angle (TIA), thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), C 7 sagittal vertical axis (C 7 SVA), T 1 pelvic angle (TPA). The Japanese Orthopaedic Association (JOA) score of cervical spine and visual analogue scale (VAS) scores of pain of cervical spine and upper extremity were compared before operation and at 12 months after operation. Pearson correlation analysis was performed on LL, PI, SS, C 7 SVA, and TPA before and after operation to evaluate the changes of spine-pelvis fitting relationship after ACDF. All 326 patients were followed up 12-32 months (mean, 18.5 months). During the follow-up period, internal fixator was in place, and no spinal cord nerve or peripheral soft tissue injury was found. JOA scores and cervical VAS scores improved significantly at 12 months after operation ( P<0.05), no significant difference was found in VAS scores of upper extremity when compared with preoperative scores ( P>0.05). The preoperative cervical VAS scores and the postoperative JOA scores at 12 months had significant differences between groups ( P<0.05). At 12 months after operation, there was no significant difference in sagittal spine-pelvis parameters in the single segment group compared with preoperative ones ( P>0.05); but the C 0-2 Cobb angle, C 2-7 Cobb angle, C 2-7 SVA, T 1S, TIA, C 7 SVA, and TPA in the double segments, three segments, and four segments groups were significant larger than preoperative ones ( P<0.05). The C 0-2 Cobb angle, C 2-7 Cobb angle, T 1S, C 7 SVA, and TPA among 4 groups had significant differences before operation and at 12 months after operation ( P<0.05). At 12 months after operation, the changes of C 7 SVA and TPA in the double segments, three segments, and four segments groups were significantly larger than those in the single segment group ( P<0.05). PI had positive correlations with LL and SS before and after operation in 4 groups ( P<0.05). Normal fitting relationship between lumbar spine and pelvis in physiological state also exists in patients with cervical spondylotic myelopathy, and ACDF can not change this specific relationship. In patients with cervical spondylotic myelopathy, the sagittal spine-pelvis sequence do not change after ACDF single-level fusion, while the sagittal spine-pelvis balance change after double-level and multi-level fusion.

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Comparison of Postoperative Analgesia Following Epidural Bupivacaine and Epidural Bupivacaine with Verapamil in Orthopaedic Lower Limb Surgeries

Efficacy of isothiocyanate-based compounds on different forms of persistent pain.

PurposeCurrent pharmacotherapy for persistent pain related to neuropathy or articular diseases is unsatisfactory, due to the large number of unresponsive patients and side effects. Isothiocyanates (ITCs) are a class of natural or synthetic compounds characterized by the general formula R–NCS. ITCs show antihyperalgesic effects in models of central and peripheral nervous tissue injury and anti-inflammatory properties. The pharmacodynamics are strictly related to the release of the gasotransmitter hydrogen sulfide (H2S) from their moiety. In particular, phenyl ITC (PITC) and 3-carboxyphenyl ITC (3C-PITC) exhibit interesting slow H2S-release properties suitable for treating painful pathology. The aim of the present work was to evaluate the efficacy of PITC and 3C-PITC against mechanical hyperalgesia and spontaneous pain induced by nerve injury and osteoarthritis.MethodsNerve injury and osteoarthritis were induced in rats by ligation of the sciatic nerve (chronic constriction injury) and intra-articular injection of monoiodoacetate, respectively. Behavioral tests were performed 14 days after damage induction.ResultsSingle subcutaneous administrations of PITC, 3C-PITC (4.43 and 13.31 µmol kg−1, respectively) were able to completely reverse hypersensitivity to noxious stimuli in both models of neuropathic and osteoarticular pain. The effect of ITCs was compared with that of NaHS, the prototypical H2S donor, showing similar efficacy and higher potency. ITCs and NaHS also reduced spontaneous pain.ConclusionITCs offer a promising novel approach to counteract persistent, drug-resistant painful pathology.

Selective inhibition of CaV3.2 channels reverses hyperexcitability of peripheral nociceptors and alleviates postsurgical pain.

Pain-sensing sensory neurons of the dorsal root ganglion (DRG) can become sensitized or hyperexcitable in response to surgically induced peripheral tissue injury. We investigated the potential role and molecular mechanisms of nociceptive ion channel dysregulation in acute pain conditions such as those resulting from skin and soft tissue incision. We used selective pharmacology, electrophysiology, and mouse genetics to link increased current densities arising from the CaV3.2 isoform of T-type calcium channels (T-channels) to nociceptive sensitization using a clinically relevant rodent model of skin and deep tissue incision. Furthermore, knockdown of the CaV3.2-targeting deubiquitinating enzyme USP5 or disruption of USP5 binding to CaV3.2 channels in peripheral nociceptors resulted in a robust antihyperalgesic effect in vivo and substantial T-current reduction in vitro. Our study provides mechanistic insight into the role of plasticity in CaV3.2 channel activity after surgical incision and identifies potential targets for perioperative pain that may greatly decrease the need for narcotics and potential for drug abuse.

Finite element modelling of complex movements during self-sealing of ring incisions in leaves of Delosperma cooperi

A numerical computer model was developed in order to describe the complex self-sealing mechanism of injured Delosperma cooperi leaves. For this purpose, the leaf anatomy was simplified to a model consisting of five concentric tissue layers. Specific parameters (modulus of elasticity, permeability, porosity, etc.) were assigned to each tissue type for modelling its physical properties. These parameters were either determined experimentally from living plant material or taken from literature. The developed computer model considers the leaf as a liquid-filled porous body within a continuum approach in order to determine the governing equations. The modelling of the wound accounts for both the injury of peripheral tissues and the free surfaces caused by the incision. The loss of water through these free surfaces initiates the self-sealing process. It is further shown that the tissue permeability and the reflection coefficient (relative permeability of a cell membrane for solutes) are the determining parameters of the self-sealing process, whereas the modulus of elasticity has a negligible influence. Thus, the self-sealing mechanism is a hydraulically driven process which leads to a local (incision region) and global (total leaf) contraction of the leaf. The accuracy of the modelled self-sealing process was validated by comparing simulation results with experiments conducted on natural plant leaves. The results will serve as valuable input for developing novel, bio-inspired technical products with self-sealing function.