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Current Opinion in Anaesthesiology Oct 2015This review outlines the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluates current knowledge regarding whether adjuvants... (Review)
Review
PURPOSE OF REVIEW
This review outlines the analgesic role of perineural adjuvants for local anesthetic nerve block injections, and evaluates current knowledge regarding whether adjuvants modulate the neurocytologic properties of local anesthetics.
RECENT FINDINGS
Perineural adjuvant medications such as dexmedetomidine, clonidine, buprenorphine, dexamethasone, and midazolam play unique analgesic roles. The dosing of these medications to prevent neurotoxicity is characterized in various cellular and in-vivo models. Much of this mitigation may be via reducing the dose of local anesthetic used while achieving equal or superior analgesia. Dose-concentration animal models have shown no evidence of deleterious effects. Clinical observations regarding blocks with combined bupivacaine-clonidine-buprenorphine-dexamethasone have shown beneficial effects on block duration and rebound pain without long-term evidence of neurotoxicity. In-vitro and in-vivo studies of perineural clonidine and dexmedetomidine show attenuation of perineural inflammatory responses generated by local anesthetics.
SUMMARY
Dexmedetomidine added as a peripheral nerve blockade adjuvant improves block duration without neurotoxic properties. The combined adjuvants clonidine, buprenorphine, and dexamethasone do not appear to alter local anesthetic neurotoxicity. Midazolam significantly increases local anesthetic neurotoxicity in vitro, but when combined with clonidine-buprenorphine-dexamethasone (sans local anesthetic) produces no in-vitro or in-vivo neurotoxicity. Further larger-species animal testing and human trials will be required to reinforce the clinical applicability of these findings.
Topics: Adjuvants, Anesthesia; Anesthetics; Humans; Nerve Block
PubMed: 26207854
DOI: 10.1097/ACO.0000000000000222 -
Journal of Neurological Surgery. Part... Apr 2016Head and neck malignancies with orbital involvement present difficult decisions to the treating physician. When the spread is perineural, the challenges are greater due... (Review)
Review
Head and neck malignancies with orbital involvement present difficult decisions to the treating physician. When the spread is perineural, the challenges are greater due to the incipient nature of the spread and the fact that the orbit can also be involved by centrifugal spread from the non-ophthalmic branches of the trigeminal nerve. The disease is often misdiagnosed and the subsequent delay in treatment results in worse outcomes. This article discusses the evaluation of the eye and the many facets of orbital involvement by perineural spread of malignancy including the treatment of complications.
PubMed: 27123389
DOI: 10.1055/s-0036-1582239 -
Frontiers in Cell and Developmental... 2020Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and... (Review)
Review
Studies have reported the vital role of nerves in tumorigenesis and cancer progression. Nerves infiltrate the tumor microenvironment thereby enhancing cancer growth and metastasis. Perineural invasion, a process by which cancer cells invade the surrounding nerves, provides an alternative route for metastasis and generation of tumor-related pain. Moreover, central and sympathetic nervous system dysfunctions and psychological stress-induced hormone network disorders may influence the malignant progression of cancer through multiple mechanisms. This reciprocal interaction between nerves and cancer cells provides novel insights into the cellular and molecular bases of tumorigenesis. In addition, they point to the potential utility of anti-neurogenic therapies. This review describes the evolving cross-talk between nerves and cancer cells, thus uncovers potential therapeutic targets for cancer.
PubMed: 33392191
DOI: 10.3389/fcell.2020.601738 -
Biomedical Papers of the Medical... Dec 2019Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One...
Oral squamous cell carcinoma (OSCC) is a growing problem worldwide. Several biological and molecular criteria have been established for making a prognosis of OSCC. One of the most important factors affecting the risk of tumor recurrence and overall prognosis is perineural invasion and bone invasion. Perineural invasion is defined as a tumor spreading and the ability of tumor cells to penetrate around or through the nerve tissue. Perineural invasion can cause the tumor to spread to distant areas from the primary tumor location. One possible explanation for this is the formation of microenvironment in the perineural space which may contain cellular factors that act on both nerve tissue and some types of tumor tissues. Bone invasion by OSCC has major implications for tumor staging, choice of treatment, outcome and quality of life. Oral SCCs invade the mandibular or maxillary bone through an erosive, infiltrative or mixed pattern that correlates with clinical behavior. Bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. Some cytokines (e.g. TNFα and PTHrP) lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression in oral SCC cells and in cancer stromal cells to induce osteoclastogenesis. Oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. A more molecular-based clinical staging and tailor-made therapy would benefit patients with bone invasion by OSCC.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Bone Neoplasms; Carcinoma, Squamous Cell; Cytokines; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nerve Sheath Neoplasms; Predictive Value of Tests; Prognosis
PubMed: 31435075
DOI: 10.5507/bp.2019.032 -
Nigerian Journal of Clinical Practice Jul 2022This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and...
BACKGROUND AND AIMS
This experimental study was designed to test the hypothesis that ondansetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor, sensory, and proprioception blockade in a dose-dependent fashion in a bupivacaine-induced sciatic nerve blockade.
MATERIALS AND METHODS
Forty-nine male Wistar Albino rats who underwent unilateral sciatic nerve block were divided into seven groups with an equal number in each group. Group B: only perineural block (PB), Group BO200: PB and perineural 200 μg ondansetron, Group BO400: PB and perineural 400 μg ondansetron, Group BO800: PB and perineural 800 μg ondansetron, Group BO800IP: PB and intraperitoneal 800 μg ondansetron, Group O800: only perineural 800 μg ondansetron, Group S: sham-operated. The rats' motor, sensory, and proprioception functions were evaluated by a blinded investigator every 10 min until they returned to normal function. The recovery times of the motor, sensory, and proprioception functions were recorded and compared. All sciatic nerves were removed and examined by electron microscopy for neurotoxic signs.
RESULTS
In which sciatic nerve block was formed with bupivacaine, the duration of the motor, sensory, and proprioception functions blockade was decreased, and the duration to return to normal functions was significantly shortened at Group BO800 (p < 0.05). According to electron microscopy results, perineural 200 μg, 400 μg, and 800 μg ondansetron were not neurotoxic.
CONCLUSION
This is the first study showing that perineural ondansetron administration (800 μg dose) reverses the effect of the local anesthetics and shortens the duration of the motor, sensory, and proprioception functions blockade.
Topics: Animals; Bupivacaine; Male; Nerve Block; Ondansetron; Rats; Rats, Wistar; Sciatic Nerve
PubMed: 35859477
DOI: 10.4103/njcp.njcp_1804_21 -
Anaesthesia Jan 2015We systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants.... (Meta-Analysis)
Meta-Analysis Review
We systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action (short- or medium- vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233 (172-295) min when injected with short- or medium-term action local anaesthetics and by 488 (419-557) min when injected with long-term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted with caution due to the extreme heterogeneity of results, with I2 exceeding 90% for both analyses. Meta-regression did not show an interaction between dose of perineural dexamethasone (4-10 mg) and duration of analgesia (r2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis.
Topics: Adjuvants, Anesthesia; Analgesia; Anesthetics, Local; Dexamethasone; Dose-Response Relationship, Drug; Humans; Nerve Block; Time Factors
PubMed: 25123271
DOI: 10.1111/anae.12823 -
Cancers Jun 2019Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and... (Review)
Review
Perineural invasion (PNI) is defined as the presence of neoplastic cells along nerves and/or within the different layers of nervous fibers: epineural, perineural and endoneural spaces. In pancreatic cancer-particularly in pancreatic ductal adenocarcinoma (PDAC)-PNI has a prevalence between 70 and 100%, surpassing any other solid tumor. PNI has been detected in the early stages of pancreatic cancer and has been associated with pain, increased tumor recurrence and diminished overall survival. Such an early, invasive and recurrent phenomenon is probably crucial for tumor growth and metastasis. PNI is a still not a uniformly characterized event; usually it is described only dichotomously ("present" or "absent"). Recently, a more detailed scoring system for PNI has been proposed, though not specific for pancreatic cancer. Previous studies have implicated several molecules and pathways in PNI, among which are secreted neurotrophins, chemokines and inflammatory cells. However, the mechanisms underlying PNI are poorly understood and several aspects are actively being investigated. In this review, we will discuss the main molecules and signaling pathways implicated in PNI and their roles in the PDAC.
PubMed: 31248001
DOI: 10.3390/cancers11070893 -
Anticancer Research Aug 2016To identify differentially expressed genes (DEGs) between perineural invasion-positive (PP) and -negative (PN) cutaneous squamous cell cancers (CSCC).
AIM
To identify differentially expressed genes (DEGs) between perineural invasion-positive (PP) and -negative (PN) cutaneous squamous cell cancers (CSCC).
MATERIALS/METHODS
Forty CSCC samples with and without perineural invasion were processed for RNA isolation and hybridization to Affymetrix-U219 DNA microarrays. Raw gene expression data were normalized by Robust Multi-array Averaging (RMA) and log2 transformed. Gene expression-based classification models were created and accuracies evaluated using leave-one-out cross-validation.
RESULTS
At a stringent limma p-value (p<0.001), 24 genes were differentially expressed between PP and PN samples. The cross-validated performance of the eight classification models exhibited a mean accuracy of 85-95%. Diagonal linear discriminant was most accurate at 95%, followed by Bayesian compound covariate at 94%. The poorest accuracy (85%) was observed for 1-Nearest neighbor and Support vector machines.
CONCLUSION
Gene expression may distinguish between PP and PN CSCC. Understanding these gene patterns may potentiate more timely diagnosis of perineural invasion and guide comprehensive therapies.
Topics: Bayes Theorem; Biomarkers, Tumor; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasms, Squamous Cell; Nerve Sheath Neoplasms; Oligonucleotide Array Sequence Analysis; Skin Neoplasms; Support Vector Machine
PubMed: 27466506
DOI: No ID Found -
Cancer Imaging : the Official... Oct 2010Perineural tumour spread refers to a contiguous neoplastic extension along a nerve. As it may be clinically silent, imaging plays a pivotal role in the evaluation and... (Review)
Review
Perineural tumour spread refers to a contiguous neoplastic extension along a nerve. As it may be clinically silent, imaging plays a pivotal role in the evaluation and delineation of perineural infiltration in head and neck malignancies, which in turn affects treatment planning. This article focuses on the imaging features of perineural spread of head and neck tumours. The important potential perineural pathways and the possible underlying pathogenesis of this phenomenon are also reviewed.
Topics: Cranial Nerve Neoplasms; Diagnosis, Differential; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 20880778
DOI: 10.1102/1470-7330.2010.9033 -
Pain Reports 2021Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in...
Analgesic effect of perineural local anesthetics, steroids, and conventional medical management for trauma and compression-related peripheral neuropathic pain: a retrospective cohort study.
INTRODUCTION
Trauma and compression are common causes of peripheral neuropathic pain (NP) refractory to conventional medical management (CMM). The role of perineural interventions in relieving this type of pain is unclear.
OBJECTIVES
The objectives of this retrospective study were to determine the analgesic benefits of adding a combination of perineural local anesthetic and steroids (LA-S) to CMM compared with CMM alone in patients who had moderate-to-severe refractory NP after trauma to the ankle and the foot.
METHODS
Health care records of 60 patients in exposed (3 injections of perineural LA-S at weekly intervals with CMM) and 60 in unexposed (CMM) cohorts were reviewed. Data on patient characteristics, pain, and mental and physical function were extracted at baseline and at the postintervention follow-up. Data were analyzed to evaluate analgesic benefit from the study interventions and the impact of baseline characteristics.
RESULTS
Perineural LA-S with CMM cohort had lower pain numerical rating scale scores at 1 to 3 months after the intervention as compared to the CMM alone cohort (5.50 [interquartile range 4.00-7.00] and 7.00 [interquartile range 5.00-8.00], respectively; < 0.01). However, multivariable analysis did not show an independent beneficial analgesic effect with the addition of perineural LA-S to CMM compared with CMM alone. A greater severity of preintervention catastrophizing (each unit increase in pain catastrophizing score increased pain score at follow-up by 0.04, 95% confidence interval: 0.01-0.07) was associated with reduction in the analgesic benefit.
CONCLUSION
Perineural local anesthetic and steroid injections do not confer an analgesic benefit for trauma- or compression-related peripheral NP.
PubMed: 34278164
DOI: 10.1097/PR9.0000000000000945