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Pain Medicine (Malden, Mass.) Mar 2017To review acute pain management strategies in patients undergoing amputation with consideration of preoperative patient factors, pharmacologic/interventional modalities,... (Review)
Review
OBJECTIVE
To review acute pain management strategies in patients undergoing amputation with consideration of preoperative patient factors, pharmacologic/interventional modalities, and multidisciplinary care models to alleviate suffering in the immediate post-amputation setting.
BACKGROUND
Regardless of surgical indication, patients undergoing amputation suffer from significant residual limb pain and phantom limb pain in the acute postoperative phase. Most studies have primarily focused on strategies to prevent persistent pain with inclusion of immediate postoperative outcomes as secondary measures. Pharmacologic agents, including gabapentin, ketamine, and calcitonin, and interventional modalities such as neuraxial and perineural catheters, have been examined in the perioperative period.
DESIGN
Focused Literature Review.
RESULTS
Pharmacologic agents (gabapentin, ketamine, calcitonin) have not shown consistent efficacy. Neuraxial analgesia has demonstrated both an opioid sparing and analgesic benefit while results have been mixed regarding perineural catheters in the immediate post-amputation setting. However, several early studies of perineural catheters employed sub-optimal techniques (distal surgical placement), and prolonged use of perineural catheters may provide a sustained benefit. Regardless of analgesic technique, a multidisciplinary approach is necessary for optimal care.
CONCLUSION
Patient-tailored analgesic regimens utilizing catheter-based techniques are essential in the acute post-amputation phase and should be implemented in all patients undergoing amputation. Future research should focus on improved measurement of acute pain and comparisons of effective analgesic regimens instead of single techniques.
Topics: Amputation, Surgical; Humans; Pain Management
PubMed: 27402960
DOI: 10.1093/pm/pnw110 -
Anaesthesia Jul 2021Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the... (Meta-Analysis)
Meta-Analysis
Both perineural and intravenous dexamethasone and dexmedetomidine are used as local anaesthetic adjuncts to enhance peripheral nerve block characteristics. However, the effects of dexamethasone and dexmedetomidine based on their administration routes have not been directly compared, and the relative extent to which each adjunct prolongs sensory blockade remains unclear. This network meta-analysis sought to compare and rank the effects of perineural and intravenous dexamethasone and dexmedetomidine as supraclavicular block adjuncts. We sought randomised trials investigating the effects of adding perineural and intravenous dexamethasone or dexmedetomidine to long-acting local anaesthetics on supraclavicular block characteristics, including time to block onset and durations of sensory, motor and analgesic blockade. Data were compared and ranked according to relative effectiveness for each outcome. Our primary outcome was sensory block duration, with a 2-h difference considered clinically important. We performed a frequentist analysis, using the GRADE framework to appraise evidence. One-hundred trials (5728 patients) were included. Expressed as mean (95%CI), the control group (local anaesthetic alone) had a duration of sensory block of 401 (366-435) min, motor block duration of 369 (330-408) min and analgesic duration of 435 (386-483) min. Compared with control, sensory block was prolonged most by intravenous dexamethasone [mean difference (95%CI) 477 (160-795) min], followed by perineural dexamethasone [411 (343-480) min] and perineural dexmedetomidine [284 (235-333) min]. Motor block was prolonged most by perineural dexamethasone [mean difference (95%CI) 294 (236-352) min], followed by intravenous dexamethasone [289 (129-448)min] and perineural dexmedetomidine [258 (212-304)min]. Analgesic duration was prolonged most by perineural dexamethasone [mean difference (95%CI) 518 (448-589) min], followed by intravenous dexamethasone [478 (277-679) min] and perineural dexmedetomidine [318 (266-371) min]. Intravenous dexmedetomidine did not prolong sensory, motor or analgesic block durations. No major network inconsistencies were found. The quality of evidence for intravenous dexamethasone, perineural dexamethasone and perineural dexmedetomidine for prolongation of supraclavicular sensory block duration was 'low', 'very low' and 'low', respectively. Regardless of route, dexamethasone as an adjunct prolonged the durations of sensory and analgesic blockade to a greater extent than dexmedetomidine. Differences in block characteristics between perineural and intravenous dexamethasone were not clinically important. Intravenous dexmedetomidine did not affect block characteristics.
Topics: Adjuvants, Anesthesia; Administration, Intravenous; Anesthetics, Local; Brachial Plexus Block; Dexamethasone; Dexmedetomidine; Humans; Network Meta-Analysis
PubMed: 33118163
DOI: 10.1111/anae.15288 -
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 -
Oral Oncology Jan 2015Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor... (Review)
Review
Perineural growth is a unique route of tumor metastasis that is associated with poor prognosis in several solid malignancies. It is diagnosed by the presence of tumor cells inside the neural space seen on histological or imaging evaluations. Little is known about molecular mechanisms involved in the growth and spread of tumor cells in neural spaces. The poor prognosis associated with perineural growth and lack of targeted approaches necessitates the study of molecular factors involved in communication between tumor and neural cells. Perineural growth rates, shown to be as high as 63% in head and neck squamous cell carcinoma (HNSCC), correlate with increased local recurrence and decreased disease-free survival. Here we describe the literature on perineural growth in HNSCC. In addition, we discuss factors implicated in perineural growth of cancer. These factors include brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 and -4, glial cell-line derived neurotrophic factor (GDNF), the neural cell adhesion molecule (NCAM), substance P (SP), and chemokines. We also explore the literature on membrane receptors, including the Trk family and the low-affinity nerve growth factor receptor. This review highlights areas for further study of the mechanisms of perineural invasion which may facilitate the identification of therapeutic targets in HNSCC.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Neoplasm Metastasis
PubMed: 25456006
DOI: 10.1016/j.oraloncology.2014.10.004 -
Cancers Sep 2021Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the highest incidence of perineural invasion (PNI), which often indicates a poor prognosis. Aggressive tumor cells invade nerves, causing neurogenic inflammation; the tumor microenvironment also induces nerves to undergo a series of structural and functional reprogramming. In turn, neurons and the surrounding glial cells promote the development of pancreatic cancer through autocrine and/or paracrine signaling. In addition, hyperalgesia in PDAC patients implies alterations of pain transmission in the peripheral and central nervous systems. Currently, the studies on this topic are relatively limited. This review will elaborate on the mechanisms of tumor-neural interactions and its possible relationship with pain from several aspects that have been focused on in recent years.
PubMed: 34572820
DOI: 10.3390/cancers13184594 -
Biochimica Et Biophysica Acta Apr 2016Pancreatic cancer is one of the most malignant human tumors. Perineural invasion, whereby a cancer cell invades the perineural spaces surrounding nerves, is acknowledged... (Review)
Review
Pancreatic cancer is one of the most malignant human tumors. Perineural invasion, whereby a cancer cell invades the perineural spaces surrounding nerves, is acknowledged as a gradual contributor to cancer aggressiveness. Furthermore, perineural invasion is considered one of the root causes of the recurrence and metastasis observed after pancreatic resection, and it is also an independent predictor of prognosis. Advanced research has demonstrated that the neural microenvironment is closely associated with perineural invasion in pancreatic cancer. Therapy targeting the molecular mechanism of perineural invasion may enable the durable clinical treatment of this formidable disease. This review provides an overview of the present status of perineural invasion, the relevant molecular mechanisms of perineural invasion, pain and hyperglycemia associated with perineural invasion in pancreatic cancer, and the targeted therapeutics based on these studies.
Topics: Chemokines; Humans; Hyperglycemia; Neoplasm Invasiveness; Pain, Intractable; Pancreatic Neoplasms; Prognosis
PubMed: 26794395
DOI: 10.1016/j.bbcan.2016.01.002 -
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 -
The Annals of Thoracic Surgery Jun 2023Lymphovascular invasion and perineural invasion are unfavorable prognostic factors in patients with esophageal squamous cell carcinoma. However, the prevalence and...
BACKGROUND
Lymphovascular invasion and perineural invasion are unfavorable prognostic factors in patients with esophageal squamous cell carcinoma. However, the prevalence and prognostic importance of lymphovascular invasion and perineural invasion after neoadjuvant chemoradiotherapy in these patients remains unclear.
METHODS
We retrospectively reviewed specimens of 321 patients with pathologically diagnosed esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy in our institution from 2017 to 2020. Lymphovascular invasion and perineural invasion were assessed by hematoxylin and eosin staining. Survival was analyzed using the log-rank test and multivariable Cox regression analysis.
RESULTS
Lymphovascular invasion and perineural invasion were present in 12.5% (n = 40) and 17.8% (n = 57) of resection specimens, respectively. Lymphovascular invasion and perineural invasion were significantly more common in patients with advanced cancer (both P < .05). In the univariate analyses, lymphovascular invasion and perineural invasion were associated with shorter overall survival and disease-free survival. Multivariable analysis revealed that lymphovascular invasion after neoadjuvant therapy was an independent adverse prognostic factor for overall survival and disease-free survival. Subgroup analyses showed that lymphovascular invasion could identify cases with worse overall survival or disease-free survival among node-negative patients, indicating the role of lymphovascular invasion in the precise staging of pN0 patients.
CONCLUSIONS
Lymphovascular invasion and perineural invasion were significantly negatively correlated with overall survival and disease-free survival. Lymphovascular invasion was an independent prognostic predictor in esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy. Lymphovascular invasion and perineural invasion should be considered in the histopathology workup for esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy; Esophageal Neoplasms; Carcinoma, Squamous Cell; Retrospective Studies; Neoplasm Staging; Prognosis; Neoplasm Invasiveness
PubMed: 36027933
DOI: 10.1016/j.athoracsur.2022.07.052 -
Pharmaceutics Nov 2019One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only... (Review)
Review
One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood-brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.
PubMed: 31726721
DOI: 10.3390/pharmaceutics11110598 -
Journal of Neurological Surgery. Part... Apr 2016Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell... (Review)
Review
Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.
PubMed: 27123384
DOI: 10.1055/s-0036-1571834