Search Results (68)

Neuropathic pain is a persistent and exhausting condition which results from damage to the nervous system and is often accompanied by emotional and cognitive impairments. In this study, we investigated dynamic changes in pain-related behaviors over 8 weeks using a spared nerve injury (SNI) model in male C57Bl/6 mice. We examined behavioral outcomes in conjunction with glial activation, neurogenesis, and glutamatergic signaling in the hippocampus to elucidate the mechanisms underlying cognitive and affective alterations associated with chronic pain. Our findings demonstrate that SNI-induced neuropathic pain progressively increases anxiety-like behavior and impairs both working and long-term memory. These behavioral deficits are accompanied by significant activation of microglia and astrocytes, a reduction in hippocampal neurogenesis, and a decrease in the expression of NMDA and AMPA glutamate receptor subunits and the scaffolding protein PSD-95. Taken together, our results suggest that hippocampal neuroinflammation and associated synaptic dysfunction contribute to the affective and cognitive disturbances observed in chronic pain, providing insight into potential molecular targets for therapeutic intervention. Full article

Chronic pain affects a significant portion of the population, with fewer than 30% achieving adequate relief from existing treatments. This study describes the humanization methodology and characterization of an effective non-opioid single-chain fragment variable (scFv) biologic that reverses pain-related behaviors, in this case by targeting P2X4. After nerve injury, ATP release activates/upregulates P2X4 receptors (P2X4R) sequestered in late endosomes, triggering a cascade of chronic pain-related events. Nine humanized scFv (hscFv) variants targeting a specific extracellular 13-amino-acid peptide fragment of human P2X4R were generated via CDR grafting. ELISA analysis revealed nanomolar binding affinities, with most humanized molecules exhibiting comparable or superior affinity compared to the original murine antibody. Octet measurements confirmed that the lead, HC3-LC3, exhibited nanomolar binding kinetics (KD = 2.5 × 10⁻⁹ M). In vivo functional validation with P2X4R hscFv reversed nerve injury-induced chronic pain-related behaviors with a single dose (0.4 mg/kg, intraperitoneal) within two weeks. The return to naïve baseline remained durably reduced > 100 days. In independent confirmation, the spared nerve injury (SNI) model was similarly reduced. This constitutes an original method whereby durable reversals of chronic nerve injury pain, anxiety and depression measures are accomplished. Full article

Background: Cold dissection (CD) during nerve-sparing robot-assisted radical prostatectomy (nsRARP) in patients with prostate cancer has been proposed to improve functional outcomes by reducing the thermal damage to neurovascular bundles (NVBs). This study compares the impact of CD versus thermal dissection (TD) on postoperative early continence and erectile function recovery. Methods: A prospective comparative analysis was conducted on patients undergoing nsRARP, comparing CD and TD techniques. Continence was assessed at 15, 30, and 90 days, while erectile function was evaluated at 30, 90, and 180 days using IIEF-5 scores. Logistic and linear regression analyses were performed to identify predictors of functional recovery. Results: CD significantly improved early continence at 15 and 30 days (p < 0.05), although the difference diminished by 90 days. Erectile function recovery was consistently higher in the CD group at all time points (p < 0.01). Age negatively impacted continence and erectile function recovery, while preoperative IIEF-5 scores were strong predictors of erectile function. Prostate volume, BMI, and metabolic syndrome showed no significant influence on outcomes. Conclusions: CD enhances early continence and erectile function recovery following nsRARP by preserving NVBs and minimizing thermal damage. This technique offers a valuable approach to improving patient functional outcomes. Further studies are required to validate its long-term benefits. Full article

Background: Distal humeral shaft fractures (DHSFs) pose surgical challenges due to the proximity to the elbow joint, limited bone stock, and the risk of radial nerve injury. This study compared clinical and radiographic outcomes of anterolateral and posterior triceps-sparing approaches to determine the most effective surgical strategy. Methods: This multicenter retrospective study included 75 patients who underwent surgery for a DHSF between 2015 and 2021, with a minimum one-year follow-up, a distal fragment ≥3 cm, and no preoperative radial nerve injury. Fifty patients underwent anterior plating via anterolateral approach, and twenty-five underwent posterior plating. Clinical and radiographic outcomes were evaluated. Results: Bone union was achieved in 74 patients (98.7%), with no significant difference between the groups (p = 0.21). The anterolateral approach resulted in a shorter operative time (116 ± 29.4 vs. 143 ± 31.4 min, p = 0.03). However, intraoperative blood loss (p = 0.36), Mayo Elbow Performance Score (p = 0.71), range of motion (p = 0.36), and complication rates (p = 0.21) were not significantly different. Two cases of transient radial nerve palsy occurred in the posterior group (p = 0.17), and four cases required implant removal due to discomfort (p = 0.18) in the anterolateral group. Conclusions: Both approaches effectively treat DHSFs with high union rates and comparable functional outcomes. However, the anterolateral approach significantly reduces operative time due to supine positioning, direct access, and avoiding radial nerve dissection. Posterior plating remains viable when stable anterior fixation is unachievable. Further studies should assess the long-term outcomes and factors influencing approach selection. Full article

Background/Objectives: This study identifies and characterizes temporal bone fractures over a five-year period at a level one trauma center, focusing on the injury mechanism, otic capsule involvement, facial nerve involvement, fracture orientation, and the impact of the COVID-19 pandemic on skull base trauma. Methods: This retrospective cross-sectional study from a single level one trauma center reviewed skull base fractures from March 2018 to July 2023, identified with ICD-10 codes. Temporal bone fractures were categorized as otic capsule-sparing or -involving and by orientation (transverse, longitudinal, or oblique). Data were grouped into before, during, and after the COVID-19 lockdown period to address the impact of the COVID-19 pandemic. Data were also grouped into facial nerve injury and no facial nerve injury. Fisher’s exact test (5% significance) and descriptive statistics were used to compare groups. Results: A total of 364 fractures were identified. Facial nerve injuries (6.1%) were more likely in otic-capsule-involving (p < 0.001) and transverse or oblique fractures (p < 0.001). During the COVID-19 lockdown, hospital stays (p = 0.011) and ICU days (p = 0.035) were shorter. Among 22 facial nerve injury cases, half received high-dose steroids, but 6 died before evaluation. Six had complete paralysis; all received steroids, and three had surgical decompression. Only two had documented recovery. Of the 10 patients with partial paralysis, 5 received steroids, but only 2 showed improvement. All patients with incomplete eye closure received protective measures. Conclusions: Temporal bone fractures involving the otic capsule or transverse/oblique patterns are more likely to result in facial nerve injury. There are treatment discrepancies, which highlight a lack of a standard approach to treating those with facial nerve injury. An analysis of the impact of the COVID-19 pandemic revealed shorter hospital and intensive care stays during this time. Full article

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]’s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management. Full article

In general, the nerve cells of the peripheral nervous system regenerate normally within a certain period after the physical damage of their axon. However, when peripheral nerves are transected by trauma or tissue extraction for cancer treatment, spontaneous nerve regeneration cannot occur. Therefore, it is necessary to perform microsurgery to connect the transected nerve directly or insert a nerve conduit to connect it. In this study, we applied human tonsillar mesenchymal stem cell (TMSC)-derived Schwann cell-like cells (TMSC-SCs) to facilitate nerve regeneration and prevent muscle atrophy after neurorrhaphy. The TMSC-SCs were manufactured in a good manufacturing practice facility and termed neuronal regeneration-promoting cells (NRPCs). A rat model of peripheral nerve injury (PNI) was generated and a mixture of NRPCs and fibrin glue was transplanted into the injured nerve after neurorrhaphy. The application of NRPCs and fibrin glue led to the efficient induction of sciatic nerve regeneration, with the sparing of gastrocnemius muscles and neuromuscular junctions. This sparing effect of NRPCs toward neuromuscular junctions might prevent muscle atrophy after neurorrhaphy. These results suggest that a mixture of NRPCs and fibrin glue may be a therapeutic candidate to enable peripheral nerve and muscle regeneration in the context of neurorrhaphy in patients with PNI. Full article

Background: Cheilectomy is a joint-sparing surgery for the treatment of moderate stages of Hallux Rigidus (HR). The purpose of this systematic review was to assess the clinical outcomes, range of motion (ROM), complications, and revision rates associated with cheilectomy. Methods: A literature search of the PubMed, Scopus, and Cochrane databases was performed. PRISMA guidelines were used. Risk of bias was assessed through the Newcastle–Ottawa Scale. Meta-analysis of the clinical outcomes scores was performed. Results: The initial search identified 317 articles, with 16 included. Cheilectomy improved ROM by 51.15% (41.23° to 62.32°), with greater gains in traditional (67.72%) vs. minimally invasive (48.74%) techniques. VAS decreased by 72.61%, more in traditional (79.35%) than minimally invasive (64.97%). AOFAS improved by 33.99%, from 61.83 to 82.85. Complications occurred in 11% (11.68% traditional, 9.73% minimally invasive), with residual pain (7.46%) more common in traditional and nerve injury (3.78%) in minimally invasive procedures. Revision rates were 7.4% overall (6.1% traditional, 8.8% minimally invasive). Conclusions: This procedure showed satisfactory results regardless of whether the traditional or minimally invasive technique is used. Current evidence does not allow for a definitive indication, but careful patient selection is advisable, particularly for mild to moderate cases. Full article

Objective(s): The objective of this study was to report our experience with a series of patients with temporal bone fractures from 2019 to 2023 and to evaluate the dilemmas in diagnosing the extent of their ontological injuries through a narrative review of the literature focusing on the classifications of temporal bone fractures. Methods: Data were collected retrospectively from the electronic medical records of patients who presented to the emergency department and were diagnosed with temporal bone fractures using computed tomograms of the head and temporal bone between September 2019 and March 2023. A total of 117 patients were included in the study. Demographic data, fracture classification, mechanism of injury, and presence and/or repair of cerebrospinal fluid (CSF) leak, facial nerve injury (both immediate and delayed), and hearing loss (both immediate and delayed) were also recorded. Results: In total, 49.5% of our cohort were between the ages of 19 and 39, and the majority (66%) were males. The primary cause of the trauma was falls in 41% of patients, followed by motor vehicle accidents (29%), and 70% had a Glasgow Coma Score (GCS) between 13 and 15 at presentation. In total, 92.3% of temporal bone fractures did not involve the otic capsule, and 79.3% were longitudinal fractures. In total, 89% of the CSF leaks were seen in patients with longitudinal fractures. Similarly, 70% of facial nerve deficits were seen in patients with longitudinal and otic capsule-sparing fractures. Conclusion: Diagnosis of facial asymmetry and hearing loss in patients with TBFs can be challenging in acute care settings but was less challenging in our cohort due to patients presenting with good GCSs. Dilemmas in clinical evaluation in the acute care setting are due to poor GCSs, heterogeneity of documentation of injuries, and classification of TBFs. Implementation of universal protocols with homogeneity in the documentation and classification of temporal bone fractures may help improve patient care and prediction of outcomes. Full article

Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedial strategy in NPP management in humans and mammals. However, past studies have investigated the underlying mechanism of the analgesic effects of EA on NPP, focusing primarily on adenosine receptors in peripheral tissues. Herein, we elucidate the role of the adenosine (Adora-3) signaling pathway in mediating pain relief through EA in the central nervous system, which is obscure in the literature and needs exploration. Specific pathogen-free (SPF) male adult mice (C57BL/6 J) were utilized to investigate the effect of EA on adenosine metabolism (CD73, ADA) and its receptor activation (Adora-3), as potential mechanisms to mitigate NPP in the central nervous system. NPP was induced via spared nerve injury (SNI). EA treatment was administered seven times post-SNI surgery, and lumber (L4–L6) spinal cord was collected to determine the molecular expression of mRNA and protein levels. In the spinal cord of mice, following EA application, the expression results revealed that EA upregulated (p < 0.05) Adora-3 and CD73 by inhibiting ADA expression. In addition, EA triggered the release of adenosine (ADO), which modulated the nociceptive responses and enhanced neuronal activation. Meanwhile, the interplay between ADO levels and EA-induced antinociception, using an Adora-3 agonist and antagonist, showed that the Adora-3 agonist IB-MECA significantly increased (p < 0.05) nociceptive thresholds and expression levels. In contrast, the antagonist MRS1523 exacerbated neuropathic pain. Furthermore, an upregulated effect of EA on Adora-3 expression was inferred when the Adora-3 antagonist was administered, and the EA treatment increased the fluorescent intensity of Adora-3 in the spinal cord. Taken together, EA effectively modulates NPP by regulating the Adora-3 signaling pathway under induced pain conditions. These findings enhance our understanding of NPP management and offer potential avenues for innovative therapeutic interventions. Full article

Background and Objectives: This study aimed to investigate the relationship between neuropathic pain and CREB-binding protein (CBP) and methyl-CpG-binding protein 2 (MeCP2) expression levels in a rat model with spared nerve injury (SNI). Materials and Methods: Rat (male Sprague-Dawley white rats) models with surgical SNI (n = 6) were prepared, and naive rats (n = 5) were used as controls. The expression levels of CBP and MeCP2 in the spinal cord and dorsal root ganglion (DRG) were compared through immunohistochemistry at 7 and 14 days after surgery. The relationship between neuropathic pain and CBP/MeCP2 was also analyzed through intrathecal siRNA administration. Results: SNI induced a significant increase in the number of CBPs in L4 compared with contralateral DRG as well as with naive rats. The number of MeCP2 cells in the dorsal horn on the ipsilateral side decreased significantly compared with the contralateral dorsal horn and the control group. SNI induced a significant decrease in the number of MeCP2 neurons in the L4 ipsilateral DRG compared with the contralateral DRG and naive rats. The intrathecal injection of CBP siRNA significantly inhibited mechanical allodynia induced by SNI compared with non-targeting siRNA treatment. MeCP2 siRNA injection showed no significant effect on mechanical allodynia. Conclusions: The results suggest that CBP and MeCP2 may play an important role in the generation of neuropathic pain following peripheral nerve injury. Full article

The nucleus accumbens shell (NAcSh) is a major structure associated with distinct aspects of reward and mnemonic information encoding, relying on spatial data to define optimal behavioral strategies. Chronic pain-derived striatal plasticity is considered one underpinning cause of working memory (WM) impairments. However, it is unclear how the NAcSh is involved in these spatial deficits. To address this, we evaluated the impact of unilateral local NAcSh electrical lesions during the execution of a food-reinforced eight-shaped spatial alternation WM task. Behavioral performance was assessed in rats after the onset of the neuropathic pain model—spared nerve injury (SNI). Our findings indicate that the induction of SNI and/or NAcSh lesions did not significantly impact the animals’ performance accuracy or motor activity during the execution of the behavioral task, but altered their response latency patterns. In addition, these manipulations did not induce significant antinociceptive effects. Collectively, these results suggest that the NAcSh may participate in specific aspects of spatial information integration and processing under neuropathic pain conditions. Full article

Purpose: The purpose of this study was to analyze the prevalence of and complications resulting from temporal bone fractures in adult and pediatric patients evaluated for cranio-facial trauma in an emergency setting. Methods: A retrospective blinded analysis of CT scans of a series of 294 consecutive adult and pediatric patients with cranio-facial trauma investigated in the emergency setting was conducted. Findings were compared between the two populations. Preliminary reports made by on-call residents were compared with the retrospective analysis, which was performed in consensus by two experienced readers and served as reference standard. Results: CT revealed 126 fractures in 116/294 (39.5%) patients, although fractures were clinically suspected only in 70/294 (23.8%); p < 0.05. Fractures were longitudinal, transverse and mixed in 69.5%, 10.3% and 19.8% of cases, respectively. Most fractures were otic-sparing fractures (95.2%). Involvement of the external auditory canal, ossicular chain and the osseous structures surrounding the facial nerve was present in 72.2%, 8.7% and 6.3% of cases, respectively. Temporal bone fractures extended into the venous sinuses/jugular foramen and carotid canal in 18.3% and 17.5% of cases, respectively. Vascular injuries (carotid dissection and venous thrombosis) were more common in children than in adults (13.6% versus 5.3%); however, the observed difference did not reach statistical significance. 79.5% of patients with temporal bone fractures had both brain injuries and fractures of the facial bones and cranial vault. Brain injuries were more common in adults (90.4%) than in children (63.6%), p = 0.001. Although on-call residents reliably detected temporal bone fractures (sensitivity = 92.8%), they often missed trauma-associated ossicular dislocation (sensitivity = 27.3%). Conclusions: Temporal bone fractures and related complications are common in patients with cranio-facial trauma and need to be thoroughly looked for; the pattern of associated injuries is slightly different in children and in adults. Full article

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA’s specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-β), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1^−/− groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain. Full article

Radical hysterectomy is a central surgical procedure in gynecological oncology. A nerve-sparing approach is essential to minimize complications from iatrogenic injury to the pelvic nerves, resulting in postoperative urinary, anorectal, and sexual dysfunction. The hypogastric plexus (HP), a complex network of sympathetic and parasympathetic nerves, plays a critical role in pelvic autonomic innervation. This article offers a comprehensive overview of the surgical anatomy of the HP and provides a step-by-step description of HP dissection, with a particular emphasis on preserving the bladder nerve branches of the inferior HP. A thorough understanding and mastery of the anatomical and surgical nuances of HP dissection are crucial for optimizing outcomes in nerve-sparing gynecologic-oncological procedures. Full article