bims-netuvo 2025-10-19 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2025–10–19
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.
Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.
Clinicopathological significance and prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: a single-center, retrospective study.
Predictive value of 18F-FDG PET/CT metabolic heterogeneity parameter combined with peritumoral adipose tissue abnormality and cN stage in perineural invasion of colorectal cancer: a retrospective analysis.
Periostin-positive stellate cells associated with perineural invasion in pancreatic adenocarcinoma.
Perineural Invasion Worsens Long-Term Outcomes of Pancreatic Neuroendocrine Tumors Following Surgical Resection.
Recombinant Human Neuregulin1-β1 Significantly Reduces Schwannoma Growth in Mice.
Multiparametric MRI characteristics for differentiating primary cancer origin in brain metastases.
Single-cell and bulk RNA-sequencing reveal PRRX2-driven cancer-associated fibroblast-mediated perineural invasion for predicting the immunotherapy outcome in colorectal cancer.
Chronic stress in cancer development and progression.
Canine spinal peripheral nerve sheath tumours in 18 dogs (2014-2023): surgical management and long-term outcomes.

Biomark Res. 2025 Oct 14. 13(1): 125

Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.

Wenting Chen, Jie Yu, Shengfang Ge, Tifei Yuan, Xianting Ding, Biao Yan, Lin Ye, Yefei Wang, Renbing Jia.

  The role of innervation in the pathogenesis of malignancies has been documented in many investigations. Recent studies have revealed that neurotransmitters act as mediators in nerve-stimulated cancer progression by directly influencing tumor cells and modulating the tumor microenvironment, including immune cells, angiogenesis, and surrounding stromal cells. Notably, psychological stress has been identified as a contributing factor to oncogenesis, primarily mediated by neurotransmitters. However, the complex interplay between neurotransmitters and tumor cells remains only partially understood. In this review, we explore newly identified mechanisms through which neurotransmitters (acetylcholine, glutamate, serotonin, dopamine, adrenaline, noradrenaline, γ-aminobutyric acid, neurotensin, and neuropeptide Y) regulate cancer initiation and progression, along with potential therapeutic strategies derived from these findings.

Keywords:  Cross-talk; Neurotransmitter; Tumor; Tumor microenvironment

DOI:  https://doi.org/10.1186/s40364-025-00835-6
iScience. 2025 Oct 17. 28(10): 113550

Neurodegeneration rewires the tumor microenvironment via the neuro-immune-cancer axis.

Jhommara Bautista, Emily C Coral-Riofrio, Salomé Suárez Urresta, David Palacios-Zavala, Carolina E Echeverría, Salomé Araujo-Abad, Andrés López-Cortés.

  Neurodegeneration and cancer, long considered opposing processes, neuronal loss versus uncontrolled proliferation, are increasingly recognized as mechanistically convergent. This review reframes the field by positioning neurodegeneration as an active driver of tumor evolution. Integrating insights from multi-omics, spatial transcriptomics, and neuroimmune-microbiota studies, we show how degenerating neurons disrupt DNA repair, mitochondrial function, immune regulation, and barrier integrity, thereby creating tumor-permissive niches. Particular emphasis is placed on the enteric nervous system, where neuronal loss promotes colorectal and pancreatic cancers through immune suppression and microbial dysbiosis. Shared molecular regulators, including p53, Pin1, STING, and the Biglycan-IL-10-microbiota axis, exhibit dual roles, pro-apoptotic in neurons yet pro-survival in tumors, highlighting context-dependent biology. We propose a mechanistic, target-based therapeutic classification that transcends disease boundaries. Recognizing neurodegeneration as a tumor-promoting process uncovers novel diagnostic and therapeutic opportunities, expanding cancer neuroscience beyond its current paradigm.

Keywords:  Cancer; Immunology; Neuroscience

DOI:  https://doi.org/10.1016/j.isci.2025.113550
Hum Pathol. 2025 10 10. pii: S0046-8177(25)00239-4. [Epub ahead of print] 105952

Clinicopathological significance and prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: a single-center, retrospective study.

Shota Kami, Motohiro Kojima, Masashi Kudo, Hajime Kamiya, Norikazu Une, Yukiko Sasahara, Motokazu Sugimoto, Shin Kobayashi, Masaru Konishi, Naoto Gotohda.

  Perineural invasion (PNI) is a recognized prognostic factor in various malignancies, but its clinical relevance in intrahepatic cholangiocarcinoma (ICC) remains unclear. This retrospective study aimed to evaluate the impact of PNI on clinical outcomes in patients with ICC who underwent liver resection between April 2009 and December 2023. Patients who underwent lymphadenectomy or extrahepatic bile duct resection were excluded. PNI was defined as tumor invasion or spread along peripheral nerve bundles within the Glissonean sheath. A total of 52 patients were included, with 26 (50.0%) identified as PNI-positive. Compared to PNI-negative patients, those with PNI had a significantly worse overall survival (OS) (5-year OS: 50.0% vs. 85.8%, P = 0.036) and recurrence-free survival (RFS) (5-year RFS: 14.5% vs. 46.8%, P = 0.010). Univariate analysis identified PNI as a risk factor for a poor OS, although this was not significant in multivariate analysis. Both PNI and portal vein invasion were independent predictors of poor RFS. Subgroup analysis revealed that postoperative adjuvant therapy significantly improved RFS in PNI-positive patients (3-year RFS: 53.6% vs. 11.1%, P = 0.036), while no such benefit was observed in PNI-negative patients. These findings suggest that PNI is a clinically relevant prognostic marker in ICC and may help identify patients who could benefit from postoperative adjuvant therapy. Routine assessment of PNI should be incorporated into pathological evaluations following ICC resection.

Keywords:  adjuvant therapy; intrahepatic cholangiocarcinoma; liver resection; pathological feature; perineural invasion

DOI:  https://doi.org/10.1016/j.humpath.2025.105952
Quant Imaging Med Surg. 2025 Oct 01. 15(10): 9600-9612

Predictive value of 18F-FDG PET/CT metabolic heterogeneity parameter combined with peritumoral adipose tissue abnormality and cN stage in perineural invasion of colorectal cancer: a retrospective analysis.

Qiaoliang Chen, Shuangxiu Tan, Jing Chen, Jiaxin Yin, Qing Sun, Di Liang, Lian Wang, Aimei Li, Jian He.

   Background: Colorectal cancer (CRC) is among the most prevalent malignant neoplasms within the digestive system. Perineural invasion (PNI) is a significant predictor of CRC prognosis, thus the crucial need to predict PNI status prior to surgical intervention. The aim of this study was to explore the efficacy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in predicting PNI status prior to surgery in CRC patients.
Methods: This study involved the retrospective collection of 18F-FDG PET/CT data from 116 CRC patients who received treatment at our facility between January 2016 and July 2024. All patients, including 50 in the PNI group and 66 in the non-PNI group, had a surgical pathological diagnosis of PNI. The primary CRC lesions were identified and their parameters calculated using LIFEx software. A peritumoral adipose tissue (PAT) grade was established by assessing the horizontal, vertical, and severity of PAT on CT images. Variables with statistically significant differences between groups were identified by univariate analysis, and independent risk factors for predicting PNI were obtained using multivariate logistic regression analysis. A nomogram model was then established. Each parameter's predictive efficiency was assessed using receiver operating characteristic (ROC) curve analysis, and the nomogram model's accuracy and clinical value were evaluated using calibration curves and decision curve analysis (DCA).
Results: According to univariate analysis, the PNI group and the non-PNI group differed statistically significantly in the metabolic tumor volume (MTV) 40% (P=0.027), the total lesion glycolysis (TLG) 40% (P=0.027), TLG60% (P=0.033), the coefficients of variation (CV) (P<0.001), the heterogeneity index (HF) (P=0.021), PAT grade (P=0.002), cN stage (P<0.001), and cM stage (P=0.016). The results of the multivariate logistic regression analysis identified the following variables as independent risk factors for predicting PNI: CV [odds ratio (OR) =3.128, 95% confidence interval (CI): 1.476-6.628, P=0.003], PAT grade (PAT grade 2: OR =12.016, 95% CI: 2.859-50.509, P<0.001; PAT grade 3: OR =22.417, 95% CI: 4.291-117.104, P<0.001), and cN stage (OR =4.769, 95% CI: 1.636-13.900, P=0.004). The ROC curve indicated an area under the curve (AUC) value of 0.893 (95% CI: 0.837-0.949) for the nomogram model. The internal validation concordance index (C-index) was found to be 0.861. Calibration curves and DCA demonstrated that the nomogram model exhibited both good accuracy and clinical utility.
Conclusions: 18F-FDG PET/CT demonstrated predictive value for PNI in CRC. Additionally, the CV, PAT grade, and cN stage were identified as independent risk factors for PNI. The nomogram model exhibited strong predictive performance.

Keywords:  Colorectal cancer (CRC); nomogram; perineural invasion (PNI); positron emission tomography/computed tomography (PET/CT); prediction

DOI:  https://doi.org/10.21037/qims-2025-708
Mol Cell Endocrinol. 2025 Oct 15. pii: S0303-7207(25)00229-1. [Epub ahead of print] 112678

Periostin-positive stellate cells associated with perineural invasion in pancreatic adenocarcinoma.

Carlos Alberto de Carvalho Fraga, Catarina Rosa E Silva Santos, Kayo Felipe Barbosa Lima, Gustavo Henrique Brasil Rodrigues, Caio Cesar Fernandes Nobre Porto, Maria Nathália de Menezes, Gabriel Victor Lucena da Silva, Adriana Simizo, Ana Kelly da SIlva Fernandes Duarte, Jussara Almeida de Oliveira Baggio, Amanda Karine Barros Ferreira Rodrigues, Karol Fireman de Farias, Elaine Virginia Martins de Souza Figueiredo, Carolinne de Sales Marques, Pedro Luiz Serrano Uson Junior, Paulo Vidal Campregher, Helder I Nakaya.

  Perineural invasion (PNI) is a hallmark of pancreatic ductal adenocarcinoma (PDAC) associated with poor prognosis. Despite its clinical significance, the specific cellular and molecular mechanisms driving PNI in PDAC remain poorly defined. In this study, we analyzed transcriptomic data from approximately 60,000 single cells across 24 PDAC biopsy specimens to characterize the cellular composition and signaling networks associated with PNI. We found that pancreatic stellate cells (PSCs) expressing high levels of Periostin (POSTN), collagens, and metalloproteinases are enriched in PNI-positive samples, suggesting an active role in extracellular matrix remodeling and tumor invasion. Spatial transcriptomics revealed that these POSTN+ PSCs are located adjacent to tumor cells in invasive regions but are more distant in non-invasive samples. Invasive tumors show a coordinated expression pattern involving ANXA1 in tumor cells, SPP1 and PLAU in PSCs, and their receptors in myeloid cells, supporting a signaling axis that promotes perineural invasion. This spatial arrangement indicates that POSTN+ PSCs are not merely bystanders but active participants in driving tumor infiltration and perineural dissemination. Together, these findings reveal coordinated multicellular programs that underlie tumor invasion and spread in PDAC, offering new insights into its aggressive biology.

Keywords:  metastasis; microenviroment; scRNA; spatial transcriptomics

DOI:  https://doi.org/10.1016/j.mce.2025.112678
Ann Surg Oncol. 2025 Oct 16.

Perineural Invasion Worsens Long-Term Outcomes of Pancreatic Neuroendocrine Tumors Following Surgical Resection.

Hui Xu, Jing-Jing Hou, Jun-Xi Xiang, Alexandra G Lopez-Aguiar, George Poultsides, Flavio Rocha, Sharon Weber, Ryan Fields, Kamran Idrees, Cliff Cho, Shishir K Maithel, Yi Lv, Xu-Feng Zhang, Timothy M Pawlik.

BACKGROUND: To define the impact of perineural invasion (PNI) on long-term survival of patients following curative-intent resection of pancreatic neuroendocrine tumors (pNETs).
PATIENTS AND METHODS: Patients with pNETs who underwent curative-intent resection (R0/R1) between 2000 and 2020 were identified from a multi-institutional database. The impacts of PNI on overall survival (OS) and disease-free survival (DFS) were analyzed.
RESULTS: Among 700 patients, 171 (n = 24.4%) had a pNET with PNI. The presence of PNI was associated with higher tumor grade (G3, 8.2% vs. 2.5%, p < 0.001), more advanced AJCC T disease (T3-T4, 58.5% vs. 15.9%, p < 0.001), and a higher incidence of nodal metastasis (52.6% vs. 21.2%, p < 0.001) versus patients with no PNI. Patients with PNI had a worse OS (median, with PNI 115.9 months vs. no PNI not reached, p < 0.001) and DFS (median, with PNI 51.9 vs. no PNI 115.4 months, p < 0.001) versus patients with no PNI. On multivariable analysis PNI was an independent risk factor associated with worse OS (HR = 2.624, 95%CI 1.475-4.668, p = 0.001), as well as DFS (HR = 1.972, 95%CI 1.396-2.786, p < 0.001). Among 256 patients with very early staged tumors (G1N0) who underwent an R0 resection, PNI remained a strong independent factor associated with worse long-term survivals (OS, HR = 3.892, 95%CI 1.196-12.662, p = 0.024; DFS, HR = 2.530, 95%CI 1.010-6.339, p = 0.048).
CONCLUSIONS: PNI was an independent adverse prognostic factor among patients undergoing curative-intent resection of pNETs, even among individuals with early-stage disease. The presence of PNI should be routinely assessed and considered in the prognostic stratification of patients following resection of pNETs.

DOI: https://doi.org/10.1245/s10434-025-18561-6
Ann Neurol. 2025 Oct 17.

Recombinant Human Neuregulin1-β1 Significantly Reduces Schwannoma Growth in Mice.

Julia P Bischoff, Alexander Schulz, Christian Hagel, Robert Büttner, Michael Reuter, Waylan K Bessler, D Wade Clapp, Helen Morrison.

OBJECTIVE: Schwannomas are benign tumors that arise from Schwann cells of the nerve sheath, and their management presents a significant clinical challenge, particularly in genetic conditions like NF2-related schwannomatosis (NF2-SWN). Although current treatments, including surgery, radiation, and repurposed pharmacological agents, can be effective, they are often limited by issues such as tumor recurrence and the risk of nerve function impairment. This study aims to evaluate the potential of recombinant human Neuregulin1 beta 1 (rhNRGβ1) to inhibit schwannoma growth and promote Schwann cell differentiation in preclinical models.
METHODS: We investigated the therapeutic potential of rhNRGβ1, a recombinant human epidermal growth factor (EGF)-like domain of Neuregulin1 beta 1, as a growth-inhibitory agent for schwannomas. Two distinct mouse models were used to assess its efficacy, with both histological and functional endpoints analyzed.
RESULTS: Both systemic and local administration of rhNRGβ1 resulted in a significant reduction in schwannoma tumor growth. Mechanistically, rhNRGβ1 not only inhibited tumor proliferation, but also promoted the differentiation of both proliferative and de-differentiated Schwann cells, suggesting a dual action of growth inhibition and cellular maturation.
INTERPRETATION: These findings highlight the therapeutic potential of rhNRG1-β1 in managing schwannomas, not only by reducing tumor growth, but also by promoting the maturation and functional restoration of Schwann cells. This dual effect provides a promising avenue for novel therapeutic strategies aimed at addressing both the growth and cellular differentiation challenges associated with schwannomas in NF2-SWN and other related conditions. ANN NEUROL 2025.

DOI: https://doi.org/10.1002/ana.78050
BMC Med Imaging. 2025 Oct 15. 25(1): 415

Multiparametric MRI characteristics for differentiating primary cancer origin in brain metastases.

Ali Salbas, Mehmet Coskun, Yusuf Kenan Cetinoglu, Merve Horoz, Murat Yogurtcu, Anil Huvez, Mustafa Fazil Gelal.

   BACKGROUND: Accurate identification of primary cancer origin in brain metastases (BMs) is crucial for diagnosis and treatment planning. Identification is challenging, particularly in unknown primary cases. Multiparametric Magnetic Resonance Imaging (MRI) offers non-invasive imaging characteristics as diagnostic clues. This study aimed to investigate the relationship between multiparametric MRI features of BMs and their primary tumor origin.
METHODS: This retrospective study included 125 patients with intra-axial brain metastases, classified as breast cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), malignant melanoma, and other cancers. Multiparametric MRI, including T2-FLAIR, contrast-enhanced 3D T1-weighted imaging, apparent diffusion coefficient (ADC) maps, susceptibility-weighted imaging (SWI), and cerebral blood volume (CBV) maps, was performed. Lesion volume, necrotic volume, necrosis ratio, peritumoral edema volume, and edema ratio were measured. 3D Slicer® software was used for semi-automated volumetric measurements. Quantitative ADC and rCBV values, intratumoral susceptibility signal (ITSS) scores, and metastasis number and location were analyzed to differentiate primary tumor origins.
RESULTS: 291 metastatic lesions from 125 patients were analyzed. NSCLC metastases showed significantly higher necrosis ratios than breast (p < 0.001) and SCLC (p = 0.025) metastases. Malignant melanoma metastases exhibited significantly higher edema ratios than breast (p = 0.001) and SCLC (p = 0.004) metastases. NSCLC metastases also showed a significantly higher edema ratio than breast (p = 0.011) metastases. Mean ADC values were significantly higher in NSCLC metastases compared to all other groups, with an optimal cut-off of ≥ 0.905 mm²/s (AUC: 0.775). Malignant melanoma and SCLC metastases had significantly higher rCBV values than breast cancer metastases. Malignant melanoma metastases consistently showed the highest ITSS scores among all groups, with an optimal cut-off of ≥ 1 (AUC: 0.769). Furthermore, multiple metastases ≤ 0.5 cm³ were significantly associated with breast cancer (p = 0.041). Infratentorial metastases were more prevalent in breast cancer (OR = 2.490, p = 0.001).
CONCLUSION: Brain metastases exhibit distinct multiparametric MRI characteristics by primary cancer origin. Breast cancer metastases tend to be smaller, multiple, and infratentorial. NSCLC metastases show greater necrosis and higher ADC values, while melanoma metastases demonstrate higher intratumoral susceptibility. These features offer valuable diagnostic clues for differentiating primary cancer types in patients with brain metastases.
CLINICAL TRIAL NUMBER: Not applicable.

Keywords:  ADC; Brain metastases; Breast cancer; ITSS; Lung cancer; Malignant melanoma; Necrosis; Perilesional edema; Primary tumor origin; rCBV

DOI:  https://doi.org/10.1186/s12880-025-01925-5
Front Cell Dev Biol. 2025 ;13 1620388

Single-cell and bulk RNA-sequencing reveal PRRX2-driven cancer-associated fibroblast-mediated perineural invasion for predicting the immunotherapy outcome in colorectal cancer.

Mingxiao Chen, Yue Cai, Feng Han, Bo Li, Zhou Xu, Kaili Cui, Wenqi Bai, Feng Li.

   Background: Perineural invasion (PNI) is common in a variety of solid tumors and has been identified as an important pathway promoting tumor local invasion and distant metastasis. Its presence is usually associated with increased aggressiveness, malignant biology, and a worse patient prognosis. However, its specific role and regulatory mechanisms in colorectal cancer (CRC) remain unclear.
Methods: In this study, we integrated 20 CRC single-cell transcriptome datasets, which contained 575,768 high-quality cells, and used the Scissor algorithm to map PNI phenotypes in TCGA bulk samples to the single-cell level. Nine cancer-associated fibroblast (CAF) subpopulations were identified and functionally annotated. We evaluated the clinical relevance of CAF subsets in TCGA and three independent cohorts (silu_2022, GSE39582, and GSE17536) using BayesPrism-based deconvolution. We analyzed transcriptional regulatory networks using pySCENIC and validated PRRX2 function by in vitro experiments. Immune infiltration characteristics were quantified using the ssGSEA score, and the association between the PRRX2 score and immune checkpoint inhibitor efficacy was analyzed in conjunction with two immunotherapy cohorts. In addition, we performed a drug sensitivity analysis based on the GDSC pharmacogenomics database to screen potential therapeutic agents.
Results: In this study, we systematically revealed the characteristics of the perineural invasion-associated fibroblast subsets and their regulatory mechanisms. In PNI-positive tumors, the proportion of fibroblasts was significantly increased, with the enrichment of MMP2+ myofibroblastic cancer-associated fibroblasts (myCAFs), and facilitated perineural infiltration through extracellular matrix remodeling. Further analysis revealed that PRRX2 was a core regulator of MMP2+myCAFs, promoting perineural invasion through the activation of TGF-β signaling pathways. PRRX2 knockdown significantly inhibited fibroblast proliferation, clonogenic formation, and invasive migration capacity, and it reduced TGFB1 and NGF expressions. The clinical cohort validation demonstrated a significant correlation between the PRRX2-score and advanced tumor stage, along with vascular and lympho-vascular invasion (LVI). Furthermore, patients with high PRRX2 scores had a significantly worse prognosis. In addition, patients with high PRRX2 scores responded poorly to immune checkpoint inhibitors but may be sensitive to targeted agents or antibody-coupled drugs, which may serve as potential targets for combination therapy.
Conclusion: This analysis established PRRX2-driven MMP2+myCAFs as pivotal mediators of CRC perineural invasion through TGF-β/ECM remodeling. The PRRX2 score serves as a biomarker for prognosis prediction and immunotherapy outcome.

Keywords:  PRRX2; colorectal cancer; immunotherapy; perineural invasion; single-cell RNA

DOI:  https://doi.org/10.3389/fcell.2025.1620388
Sci Bull (Beijing). 2025 Sep 22. pii: S2095-9273(25)00974-0. [Epub ahead of print]

Chronic stress in cancer development and progression.

Xin Niu, Ting Wu, Linghui Zeng, Fangwei Wang, Weiguo Lv, Long Zhang, Fangfang Zhou.

  Short-term stress positively affects homeostasis recovery; however, long-term stress leads to various diseases. Accumulating evidence shows that cancer processes are not only related to genetics and environment but also to chronic stress. For patients with cancer, the disease process induces prolonged psychological and physical stress, including fear and pain, which makes chronic stress common in patients. Chronic stress, in turn, regulates different components of the primary tumor and tumor microenvironment through a wide variety of stress mediators. Furthermore, studies indicate that chronic stress increases tumor burden and mortality in patients with different types of cancer, while the management of chronic stress can alleviate disease burden and extend patient survival. Therefore, a deeper understanding of the role and mechanism of chronic stress in cancer is necessary for developing new strategies for cancer treatment beyond traditional treatment approaches. Herein, we explored the different sources of chronic stress, the molecular mechanisms through which chronic stress affects cancer development and progression, and the stress mediators involved. We discussed the multiple impacts of chronic stress on cancer, as well as the currently available intervention strategies. We also highlighted the prospects and challenges of chronic stress management in the clinical treatment of cancer.

Keywords:  Cancer development; Cancer progression; Chronic stress; Intervention strategies; Stress mediators

DOI:  https://doi.org/10.1016/j.scib.2025.09.034
Front Vet Sci. 2025 ;12 1653812

Canine spinal peripheral nerve sheath tumours in 18 dogs (2014-2023): surgical management and long-term outcomes.

Jonathan Deacon, Jos Bongers, Catherine Stalin.

  Spinal peripheral nerve sheath tumours (PNST) commonly manifest as chronic pain, lameness, and paresis in dogs, and these conditions typically prove resistant to medical management. These tumours present significant surgical challenges due to their anatomical location and the complexity of achieving complete margins whilst minimising post-operative morbidity and complications. This single-centre retrospective study evaluated surgical outcomes in 18 dogs with histologically confirmed PNST treated between 2014 and 2023, examining the effectiveness of both amputation and compartmental resection approaches. An analysis revealed an overall median survival time (MST) of 326 days (range: 28-1,374 days), with three patients remaining alive at study conclusion. Notably, patients achieving R0 proximal margins demonstrated significantly better outcomes with longer overall survival times (range: 311-1,374 days, mean 841 days, median 850 days) compared to those with R1 margins (range: 28-1,357 days, mean 346 days, median 217 days). These findings demonstrate that surgical interventions, particularly when achieving non-infiltrated proximal margins, can provide meaningful improvements in both patient comfort and survival time for dogs affected by PNST.

Keywords:  PNST; amputation; durectomy; laminectomy; rhizotomy

DOI:  https://doi.org/10.3389/fvets.2025.1653812