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

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

Pre-Surgical Factors Influencing Post-Surgical Outcomes in Orthognathic Surgery Patients: A Longitudinal Study.

Background/Objectives: This study aims to assess the relationship between physical and psychosocial pre-surgical factors and post-surgical evolution in patients undergoing orthognathic surgery. Methods: A cohort study with 3 months of follow-up after maxillofacial surgery was conducted. Participants were recruited from the Maxillofacial Surgery Unit of Hospital Universitario La Paz in Madrid, Spain. Primary variables included the range of motion of mouth opening, protrusion tongue force, anxiety, depression and kinesiophobia. Assessments were realised on-site or via video call. Statistical analysis was conducted using mixed-effects models. Results: The initial recruitment yielded 22 patients, with 19 ultimately eligible for analysis. The study found significant impacts of pre-surgical factors on post-surgical evolution. Both ranges of motion and anxiety showed influences from baseline measures, with the range of motion affected by a pre-surgical range of motion (estimate: 3.89) and positive expectations (estimate: 4.83). Anxiety was influenced by both pre-surgical (estimate: 0.48) and baseline anxiety levels (estimate: 0.64). Kinesiophobia demonstrated a trend toward significance, with baseline levels affecting post-surgical evolution (estimate: 0.77). Conclusions: Our results highlight the relationship between pre-surgical factors and post-surgical outcomes in orthognathic surgery patients. Pre-surgical range of motion and positive expectations were found to influence post-surgical range of motion, while pre-surgical anxiety levels impacted post-surgical anxiety evolution. Pre-surgical kinesiophobia also showed potential as a post-surgical kinesiophobia predictor, but further investigation is needed to confirm this relationship.

Evaluation of post-surgical complications of hidradenitis suppurativa lesions explored with presurgical ultra-high frequency ultrasound mapping.

OBJECTIVE: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the hair follicle. Its treatment often requires a surgical approach. The aim of our study was to evaluate the occurrence of post-surgical complications following a new standard of surgical management. This included presurgical lesion mapping by ultra-high frequency ultrasound (UHFUS) with a 70MHz probe. Postoperative management was based on the principles of HS-TIME (time, inflammation/infection, moisture, edges). METHOD: A single-centre, retrospective study was conducted by the Department of Dermatology of the University of Pisa. Patients with moderate and severe HS, refractory to previous medical and surgical therapies, were enrolled. All of the patients were treated with wide surgical excision of lesions, previously explored through a UHFUS evaluation with VEVO MD (Fujifilm VisualSonics, Inc., Canada) using a 48MHz and a 70MHz ultrasound probe. Following surgery, all patients were treated with secondary intention healing following the principles of HS-TIME. For each patient, we assessed the occurrence of post-surgical complications at follow-up visit six months after surgery. For each patient we assessed the occurrence of early post-surgical complications at every follow-up visit after surgery until complete wound healing. The occurrence of delayed complications was then assessed in all patients with an observation time after complete healing of >3 months (n=23). RESULTS: A total of 26 patients were enrolled in the study. There were no reported cases of post-surgical bleeding or haematoma occurrence, while three (11.5%) patients developed minor surgical site infection. The average severity of pain decreased from a numerical rating scale of 5.3 immediately after surgery to 1.3 after four weeks. The average healing time was 33.3±16.8 days, and only five (19.2%) patients reported a complete wound healing time of >6 weeks. Focusing on delayed complications: 1/23 (4.3%) patient had hypertrophic scarring; 2/23 (8.7%) patients reported dysaesthesia; and 2/23 (8.7%) cases of clinical relapse were reported. No cases of limited mobility at the surgery site were registered. CONCLUSION: The findings of the study demonstrated the efficacy of a novel surgical protocol, including a preoperative ultrasound evaluation and appropriate postoperative wound management. Further prospective studies are needed to validate the observed results; however, we conclude that the low recurrence rates and post-surgical complications confirmed that our proposed protocol would represent an effective strategy for the management of patients with HS eligible for surgical therapy.

Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions.

Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.

Ex vivo platform en route to functional precision medicine: clinical relevance in gynecological cancers.

A scientific interrogation-driven approach to the clinical management of cancer patients is based on molecular profiling of the tumor. Empowered by the knowledge of oncogenic drivers and biomarkers, oncologists chart an optimal treatment path toward increasing the mathematical probability of a positive outcome. In this entire chain of events, an experimental proof of logical interrogation has never been incorporated before. Here, we provide the first evidence that the result of ex vivo testing of a drug matched to the genomic profiling of an N-of-1 tumor can deliver meaningful insight connecting scientific interrogation and a clinical event. Using resected tissues from endometrial (EC) and ovarian (OC) cancer patients, we designed a personalized ex vivo platform to test combinations of drugs in the default histological architecture of the individual tumors. Following the CART-T cells' principle, we co-cultured with autologous T-cells to test targeted drugs and immune checkpoint inhibitors. The study was designed with a limited clinical information window from patient registration/consent to obtaining the tumor tissues, and adjuvant treatment/post-surgery event (PSE) data were accessed retrospectively. Using a checkerboard analysis, we found that PSE-free survival time was longer in patients whose therapy "matched" the effective drug combination in ex vivo culture/co-cultures compared to those with no effect. Specifically, out of 32 EC patients in the "test & treatment-matched" category whose tumor cells failed to respond to ex vivo drug testing, none achieved > 4 and > 3 years of PSE-free survival. In contrast, out of 38 EC patients in the "test & treatment-matched" category, 4 and 6 patients, whose tumor cells responded to drugs in ex vivo culture, achieved > 4 and > 3 years of PSE-free survival, respectively. Cases with genomically-guided ex vivo testing showed that a "match" between an effective ex vivo drug combination and therapy resulted in late PSE, whereas a "match" between prescribed treatment and an ineffective drug combination in ex vivo testing led to early PSE. Our study demonstrates that integrating genomic data with personalized drug testing on an ex vivo culture/co-culture platform is an effective tool for modeling functional precision medicine in gynecological cancers. This approach bridges the gap between next-generation drug testing in translational research and patient care, providing insight for improved treatment outcomes.

"What really matters to the patients?": assessing the impact of wound healing on the quality of life in patients undergoing incisional hernia repair.

PURPOSE: We aim to evaluate the impact of surgical wound complications in the first 30 postoperative days after incisional hernia repair on the long-term quality of life of patients. In addition, the impact of the surgical technique and preoperative comorbidities on the quality of life of patients will also be evaluated. METHOD: Prospective cohort study, which evaluates 115 patients who underwent incisional hernioplasty between 2019 and 2020, using the onlay and retromuscular techniques. These patients were initially assessed with regard to surgical wound outcomes in the first 30 postoperative days (surgical site infection (SSI) or surgical site occurrence (SSO)), and then, assessed after three years, through a specific quality of life questionnaire, the Hernia Related Quality of Life Survey (HerQLes). RESULTS: After some patients were lost to follow-up during the study period, due to death, difficulty in contact, refusal to respond to the questionnaire, eighty patients were evaluated. Of these, 11 patients (13.8%) had SSI in the first 30 postoperative days and 37 (46.3%) had some type of SSO. The impact of both SSI and SSO on quality of life indices was not identified. When analyzing others variables, we observed that the Body Mass Index (BMI) had a significant impact on the patients' quality of life. Likewise, hernia size and mesh size were identified as variables related to a worse quality of life outcome. No difference was observed regarding the surgical techniques used. CONCLUSION: In the present study, no relationship was identified between surgical wound outcomes (SSO and SSI) and worse quality of life results using the HerQLes score. We observed that both BMI and the size of meshes and hernias showed an inversely proportional relationship with quality of life indices. However, more studies evaluating preoperative quality of life indices and comparing them with postoperative indices should be carried out to evaluate these correlations.

Intravenous Lidocaine for the Management of Chronic Pain: A Narrative Review of Randomized Clinical Trials.

Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.

Treatment of Refractory Vesicourethral Anastomosis Pain Following Radical Prostatectomy Using a Combination of Non-ablative Erbium:YAG and Neodymium:YAG Laser Therapy: A Case Report.

This case report describes the successful treatment of refractory vesicourethral anastomosis (VUA) pain in an 82-year-old man following radical prostatectomy using a combination of non-ablative erbium:YAG and neodymium:YAG laser therapy with Fotona SP Dynamis. Despite various conventional treatments, the patient's pain persisted, which significantly impaired his quality of life. The rationale for using laser therapy is based on its potential to promote tissue healing and nerve regeneration and reduce inflammation at the anastomosis site. The patient underwent monthly laser irradiation sessions, with the erbium:YAG laser targeting the area around the urethral anastomosis site via the anus and the neodymium:YAG laser irradiating the base of the penis and scrotum. Urethral pain gradually decreased from a visual analog scale score of 10 to 0 over the course of treatment. This highlights the importance of considering alternative approaches when conventional methods fail to provide relief. The targeted, minimally invasive nature of laser therapy may offer a safer and more effective alternative to systemic medications for managing chronic post-surgical pain. Although further research is needed to establish the generalizability and long-term effectiveness of this approach, this case provides a promising foundation for future investigations of the role of laser therapy in managing refractory VUA pain following radical prostatectomy.

The Key Ripper: a specialized fixed suture-cutting device to facilitate drain removal.

The removal of post-surgical drains requires suture cutting. We developed a novel and specialized device that can safely remove the threads fixing the drains, making drain removal safer and easier than the current removal approach using scissors or a scalpel.

Exploring the impact of rehabilitation on post-surgical recovery in elbow fracture patients: a cohort study.

INTRODUCTION: Elbow fractures, characterized by their complexity, present significant challenges in post-surgical recovery, with rehabilitation playing a critical role in functional outcomes. This study explores the efficacy of rehabilitative interventions in enhancing joint range of motion (ROM) and reducing complications following surgery for both stable and unstable elbow fractures. METHODS: A cohort of 15 patients, divided based on the stability of their elbow fractures and whether they received post-operative rehabilitation, was analyzed retrospectively. Measurements of ROM-including flexion, extension, pronation, and supination-were taken at three follow-ups: 15-, 30-, and 45-day post surgery. The study assessed the impact of rehabilitation on ROM recovery and the resolution of post-surgical complications. RESULTS: The findings indicated no statistically significant differences in ROM improvements between patients who underwent rehabilitation and those who did not, across all types of movements measured. However, early rehabilitative care was observed to potentially aid in the mitigation of complications such as joint stiffness, especially in patients with stable fractures. CONCLUSION: While rehabilitation did not universally improve ROM recovery in elbow fracture patients, it showed potential in addressing post-operative complications. The study underscores the importance of individualized rehabilitation plans and highlights the need for further research to establish evidence-based guidelines for post-surgical care in elbow fractures.

From the Metaphor of the Lizard's Tail to That of the Doughnut: A Case of Achilles Tendon Complete Regrowth.

Introduction: Tendon tissue turnover is a very slow process. However, some tendons show very unique regeneration capabilities. The Achilles tendon regeneration and maturation process occurs uniformly and centripetally along the entire the length of the neo-tendon. Case Report: The present case report describes a complete regeneration of the Achilles tendon in a 54-year-old patient with a reinjury to the Achilles tendon following open tenorrhaphy surgery. The regenerative process had a positive outcome despite the patient suffering, at the time, from an infection caused by Cutibacterium acnes. Conclusion: This case report is a paradigmatic example of how the Achilles tendon is able to maintain its regenerative capacity even in extremely critical biological situations such as after an infection. However, the issue concerning the biological characteristics of the regenerated tendon remains open.

Association of Untreated Pre-surgical Depression With Pain and Outcomes After Spinal Surgery.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: Untreated pre-surgical depression may prolong post-surgical pain and hinder recovery. However, research on the impact of untreated pre-surgical depression on post-spinal surgery pain is lacking. Therefore, this study aimed to assess pre-surgical depression in patients and analyze its relationship with post-surgical pain and overall post-surgical outcomes. METHODS: We recruited 100 patients scheduled for lumbar spine surgery due to spondylolisthesis, degenerative lumbar disc diseases, and herniated lumbar disc diseases. Psychiatrists evaluated them for the final selection. We assessed the Beck Depression Inventory (BDI), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and EuroQoL 5 Dimensions (EQ-5D) scores, numerical back and leg pain scales, and medication dosage data collected before and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Ninety-one patients were included in this study; 40 and 51 were allocated to the control and depression groups, respectively. The pre- and post-surgical leg pain, back pain, and functional scores were not different. However, the depression group showed higher ODI and EQ-5D and lower JOA scores than the control group 3 months post-surgery. Partial correlation analysis revealed an inverse correlation between the JOA and BDI scores and a positive correlation between the EQ-5D and BDI scores at 3 months postoperatively. CONCLUSION: Untreated depression can prolong postoperative pain and hinder recovery. Detecting and treating depression in patients before spine surgery may improve their overall quality of life and functional recovery.

Lysyl Oxidase-like 2 Dysregulation Increases the Risk of Post-Operative Fibrotic Scars Formation in the Female Reproductive Tract: A Novel Therapeutic Target to Reduce Fibrogenesis.

The formation of fibrotic bands in female reproductive system, including the uterus, after abdominal and pelvic surgeries, is an important medical challenge associated with many complications, including infertility and pain. Investigating the role of different molecules involved in fibrosis and adhesion formation may help in the development of new drugs to prevent this disorder. Lysyl oxidase-like 2 (LoxL2) is a copper-dependent enzyme that catalyzes the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM) to stabilize ECM. Dysregulation of LoxL2 activity resulting from tissue hypoxia and inflammation after gynecological surgeries in the female reproductive tract increases collagen fibers cross-linking and promotes fibrosis. It has been shown that targeting LoxL2 by Lox inhibitors may reduce fibrosis. Considering the expression of LoxL2 in female reproductive organs and its dysregulation in hypoxia and inflammation, it is possible that LoxL2 has therapeutic potential as a drug target in the prevention of adhesions. In this review, we discuss the role of LoxL2 in the promotion of fibrotic processes focusing on its link with inflammatory and hypoxic conditions. We also justify the use of anti- LoxL2 agents as a potential therapeutic strategy for the prevention of post-surgical scar formation.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

The Therapeutic Potential of Targeting the Connexin43 as a New Approach to Reducing Post-Surgical Adhesion.

Post-surgical peritoneal adhesions are a serious problem causing complications, such as bowel obstruction, infertility, and pain. There are currently no effective ways of preventing post-surgical adhesions. Excess secretion of proinflammatory cytokines and profibrotic molecules by immune cells and adherent fibroblasts is the main mechanism thatpromotes post-operative fibrotic scars. Although many studies have been conducted on the pathological causes of this disorder, there are still many unknown facts in this matter, so assessment of the role of different molecules in causing inflammation and adhesion can lead to the creation of new treatment methods. Connexins are a group of proteins related to gap junctions that have a role in cell communication and transmitted signaling between adjacent cells. Between different types of connexin protein isoforms, connexin43 is known to be involved in pathological conditions related to inflammation and fibrosis. Recent studies have reported that inhibition of connexin43 has the potential to reduce inflammation and fibrosis by reducing the expression of molecules like α-SMA and plasminogen activator inhibitor (PAI) that are involved in the early stages of adhesion formation. Further, inhibition of connexin43 may have therapeutic potential as a target to prevent post-surgical peritoneal adhesions.

Pre-Pandemic Predictivity of Anxious-Depressive Symptoms in Post-Surgical Traumatic Distress in Hysterectomy for Benign Disease and COVID-19 Outbreak: A Case-Control Study.

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic led to several needed containment measures that conditioned the onset of depressive, anxiety, and post-traumatic stress symptoms in the population. These symptoms, especially if not diagnosed and treated, can also occur in patients undergoing medical care or surgery, with a high impact on people's lives and causing low adherence to treatment. The study evaluates whether the spread of the coronavirus disease 2019 (COVID-19) worsened the onset of post-surgical distress and symptoms of anxiety and depression in a population undergoing hysterectomy for benign disease during the pandemic era, comparing it with a population with the same characteristics but recruited before COVID-19. Methods: The sample was evaluated before surgery (T1), post-operatively (T2), and 3 months after surgery (T3) through a sociodemographic questionnaire and through the HADS (Hospital Anxiety and Depression Scale) to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) to assess the onset of post-surgical distress. Results: Patients treated after the COVID-19 pandemic showed a higher depressive symptoms rate compared with those treated before (p-value = 0.02); conversely, pre-COVID-19 patients were more prone to develop post-traumatic stress disorder (PTSD) (p-value = 0.04). A significant association between the occurrence of PTSD and anxiety-depressive symptoms registered at T2 (p-value = 0.007) and T3 (p-value < 0.0001) emerged. In the end, the COVID-19 pandemic has exerted a detrimental influence on the mental well-being of the patients under investigation, with a notable exacerbation of their mood disturbances. Conclusions: The findings advocate for the implementation of psychometric and psychodiagnostic assessments to promptly detect high-risk scenarios that could lead to PTSD, compromising treatment compliance and exacerbating the overall outcome, resulting in substantial direct and indirect burdens.

Pulsed electromagnetic fields (PEMF) as a valid tool in orthognathic surgery to reduce post-operative pain and swelling: a prospective study.

PURPOSE: PEMF (pulsed electromagnetic fields) founds application in several medical fields to accelerate bone wounds healing and to reduce inflammation. The aim of our study was to evaluate the effectiveness of PEMF in reducing postoperative swelling and pain in patients undergoing orthognathic surgery. METHODS: A prospective observational monocentric study was conducted on a sample of 30 patients undergone to orthognathic surgery in Maxillofacial Surgery Unit of University of Naples Federico II. The patients who followed these inclusion criteria were enrolled in the study: age ≥ 18 years, Class III malocclusion, Surgical procedure of Le Fort I osteotomy + Bilateral Sagittal Split Osteotomy (BSSO), Written informed consent. Patients were divided into two groups: Group SD) postoperative standard treatment with medical therapy and cryotherapy, Group SD + PEMF) postoperative standard therapy + PEMF. Each patient underwent a 3D facial scan, at one (1d) and four (4d) days after surgery to compare the swelling reduction. The pain score was assessed through VAS score and analgesics administration amount. RESULTS: In SD + PEMF group, the facial volume reduction between 1d and 4d scan was on average 56.2 ml (6.23%), while in SD group, it was 23.6 ml (2.63%). The difference between the two groups was 3.6% (p = 0.0168). VAS pain values were significantly higher in SD group compared to SD + PEMF group in the second day after surgery (P = 0.021) and in the total 4 days (P = 0.008). CONCLUSIONS: Our data suggest that PEMF is valid tool to promote faster postoperative swelling and pain reduction in patients undergoing orthognathic surgery.

Novel Scorpion Toxin ω-Buthitoxin-Hf1a Selectively Inhibits Calcium Influx via CaV3.3 and CaV3.2 and Alleviates Allodynia in a Mouse Model of Acute Postsurgical Pain.

Venom peptides have evolved to target a wide range of membrane proteins through diverse mechanisms of action and structures, providing promising therapeutic leads for diseases, including pain, epilepsy, and cancer, as well as unique probes of ion channel structure-function. In this work, a high-throughput FLIPR window current screening assay on T-type CaV3.2 guided the isolation of a novel peptide named ω-Buthitoxin-Hf1a from scorpion Hottentotta franzwerneri crude venom. At only 10 amino acid residues with one disulfide bond, it is not only the smallest venom peptide known to target T-type CaVs but also the smallest structured scorpion venom peptide yet discovered. Synthetic Hf1a peptides were prepared with C-terminal amidation (Hf1a-NH2) or a free C-terminus (Hf1a-OH). Electrophysiological characterization revealed Hf1a-NH2 to be a concentration-dependent partial inhibitor of CaV3.2 (IC50 = 1.18 µM) and CaV3.3 (IC50 = 0.49 µM) depolarized currents but was ineffective at CaV3.1. Hf1a-OH did not show activity against any of the three T-type subtypes. Additionally, neither form showed activity against N-type CaV2.2 or L-type calcium channels. The three-dimensional structure of Hf1a-NH2 was determined using NMR spectroscopy and used in docking studies to predict its binding site at CaV3.2 and CaV3.3. As both CaV3.2 and CaV3.3 have been implicated in peripheral pain signaling, the analgesic potential of Hf1a-NH2 was explored in vivo in a mouse model of incision-induced acute post-surgical pain. Consistent with this role, Hf1a-NH2 produced antiallodynia in both mechanical and thermal pain.

Advancing Novel Strategies against Post-surgical Tendon Adhesion Bands, Exploring New Frontiers.

Current interest in adhesion formation stems from its global impact on the function and quality of life, spanning a spectrum of subtle impairments to significant disabilities, based on the affected area and the extent of adhesion. Yet therapeutic agents are restricted to prophylactic anti-inflammatories, revision surgeries, and biological and physical techniques, none of which grant a decent outcome. Recent advancements in tissue- engineered biomaterials, drug delivery systems, and fabricating technologies such as nanoparticles, hydrogels, and weaving or braiding demonstrate potential for improved outcomes. However, none of the mentioned methods have reliable outcomes, thus this study aims to elucidate the mechanisms involved in the pathophysiology of tendon adhesion and post-surgical adhesion band formation (PSAB), with a closer look at inflammatory pathways stimulating the process. This article consolidates information on diverse therapeutic and prophylactic methods and cutting-edge technologies, aiming to provide a comprehensive update on this topic, and providing researchers an avenue for new and innovative ideas for further investigations.

Intra-peritoneal lavage of Zingiber officinale rhizome and its active constituent gingerol impede inflammation, angiogenesis, and fibrosis following post-operative peritoneal adhesion in male rats.

Post-operative peritoneal adhesions (PA) are a common and important clinical problem. In this study, we focused on the ameliorative efficacy of ginger and gingerol compounds on surgical-induced peritoneal adhesion, and their strategies that disrupted the PA formation pathways to suppress their incidence. First, liquid chromatography-mass spectrometry (LC-MS) was established to separate and identify several chemical groups of ginger rhizome extract. In the next steps, male Wistar albino rats were randomly selected and divided into various groups, namely sham, control, ginger extract (0.6, 1.8, 5 %w/v), and gingerol (0.05, 0.1, 0.3, and 1 %w/v). Finally, we investigated the macroscopic parameters such as wound healing, body weight as well as spleen height and weight. In addition, visual peritoneal adhesion assessment was performed via Nair et al and Adhesion Scoring Scheme. Moreover, the microscopic parameters and biological assessment was performed via and immunoassays. The present findings revealed significant improvement in wound healing and reduction of the adhesion range, as Nair et al. and Adhesion Scoring Scheme scoring, in both the ginger and gingerol groups compared to the PA group (P < 0.05). Whereas, gingerol (0.3 % w/v) was able to increase the body weight in rats (P < 0.0001) at end stage of experiment. Also, inflammation, angiogenesis, and fibrosis were significantly decreased due to the downregulation of interleukin (IL)-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, vascular endothelial growth factor (VEGF), respectively, in the ginger and gingerol groups compared to the PA group (P < 0.05). In contrast, the levels of IL-10 were increased in the ginger and gingerol groups compared to the control group (P < 0.01). Our results proved that ginger rhizome and gingerol, as novel therapeutic compounds, could be used to prevent PA for their beneficial anti-inflammatory as well as anti-fibrosis properties in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger and gingerol.