scholarly journals Bone Metastasis Pain, from the Bench to the Bedside

2019 ◽  
Vol 20 (2) ◽  
pp. 280 ◽  
Author(s):  
Federica Aielli ◽  
Marco Ponzetti ◽  
Nadia Rucci

Bone is the most frequent site of metastasis of the most common cancers in men and women. Bone metastasis incidence has been steadily increasing over the years, mainly because of higher life expectancy in oncologic patients. Although bone metastases are sometimes asymptomatic, their consequences are most often devastating, impairing both life quality and expectancy, due to the occurrence of the skeletal-related events, including bone fractures, hypercalcemia and spinal cord compression. Up to 75% of patients endure crippling cancer-induced bone pain (CIBP), against which we have very few weapons. This review’s purpose is to discuss the molecular and cellular mechanisms that lead to CIBP, including how cancer cells convert the bone “virtuous cycle” into a cancer-fuelling “vicious cycle”, and how this leads to the release of molecular mediators of pain, including protons, neurotrophins, interleukins, chemokines and ATP. Preclinical tests and assays to evaluate CIBP, including the incapacitance tester (in vivo), and neuron/glial activation in the dorsal root ganglia/spinal cord (ex vivo) will also be presented. Furthermore, current therapeutic options for CIBP are quite limited and nonspecific and they will also be discussed, along with up-and-coming options that may render CIBP easier to treat and let patients forget they are patients.

Author(s):  
Juan P. Cata

Metastatic spinal cord compression (MSCC) is a medical emergency that requires early diagnosis and treatment. Medical management or surgery can be indicated depending on different factors including duration of the symptoms, patient comorbidities, and hospital resources. Patients scheduled for decompressive laminectomy due to MSCC may present to the operating room with pain, high requirements of opioids, hematological disorders, impending bone fractures, nausea and vomiting, and electrolytes disorders. Multimodal intraoperative monitoring is needed to minimize spinal cord injury. The immediate postoperative care of these patients is directed to accelerate recovery by providing multimodal analgesia, encouraging early ambulation, and optimizing their nutritional status.


1993 ◽  
Vol 78 (6) ◽  
pp. 929-937 ◽  
Author(s):  
Tali Siegal ◽  
Tzony Siegal

✓ The effects of differing strategies of serotonergic manipulation on vascular permeability, prostaglandin E2 (PGE2) synthesis, and the clinical course are evaluated in an experimental model of neoplastic spinal cord compression in rats. Serotonergic manipulations include in vivo inhibition of serotonin (5-HT) synthesis by p-chlorophenylalanine (p-CPA) and in vivo blockage of serotonin type 2 (5-HT2) receptors either by the selective antagonist ketanserin or by cyproheptadine. In paralyzed rats, the ratio of 5-hydroxyindole-3-acetic acid (5-HIAA) to 5-HT is significantly elevated in the compressed segments, suggesting that 5-HT utilization is increased. Treatment with p-CPA attenuates spinal 5-HT levels by 62.8% ± 5.1% (mean ± standard deviation) and reduces the elevated 5-HIAA:5-HT ratio to the normal value. The increased synthesis of PGE2 observed in the compressed cord is unaffected by p-CPA or ketanserin treatment but is markedly attenuated by cyproheptadine. Ketanserin reduces the 10-fold increase in spinal cord permeability observed in paralyzed rats in a clearly dose-related manner. If given at the first sign of neurological dysfunction, ketanserin delays the onset of paraplegia with the 1-mg/kg dose being clearly superior. Cyproheptadine and p-CPA also reduce the increased permeability and protract the course to paraplegia. A comparison of the effect of dexamethasone, indomethacin, cyproheptadine, p-CPA, and ketanserin reveals that they protract the disease course by 48%, 57%, 60%, 64%, and 78%, respectively. These data suggest that 5-HT2 receptors mediate some of the deleterious vascular consequences observed in the compressed spinal cord by a mechanism not coupled with PGE2 synthesis. A potential benefit of serotonergic manipulations for the acute treatment of neoplastic spinal cord compression is suggested.


2017 ◽  
Vol 3 (2) ◽  
pp. 176-183 ◽  
Author(s):  
Stephan Duetzmann ◽  
Ulrich Pilatus ◽  
Volker Seifert ◽  
Gerhard Marquardt ◽  
Matthias Setzer

2020 ◽  
Vol 117 (30) ◽  
pp. 18018-18028
Author(s):  
Nira de la Vega Gallardo ◽  
Rosana Penalva ◽  
Marie Dittmer ◽  
Michelle Naughton ◽  
John Falconer ◽  
...  

CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3−/−mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.


Author(s):  
L Ascari ◽  
C Stefanini ◽  
U Bertocchi ◽  
P Dario

This work presents the design and development of an integrated image-guided robot-assisted endoscopic system for the safe navigation within the spinal subarachnoid space, providing the surgeon with the direct vision of the structures (i.e. spinal cord, roots, vessels) and the possibility of performing some particularly useful operations, like local electrostimulation of nerve roots. The modelling, micro-fabrication, fluidic sustentation, and cable-based actuation system of a steerable tip for a multilumen flexible catheter is described; the hierarchical control system shared between the surgeon and the computer, and based on machine vision techniques and a simple but effective three-dimensional reconstruction is detailed. The Blind Expected Perception sensory-motor scheme is proposed in robot-assited endoscopy. Results from in vitro, ex vivo, and in vivo experiments show that the described model can accurately predict the shape of the catheter given the tension distribution on the cables, that the proposed actuation system can assure smooth and precise control of the catheter tip, that the fluidic sustentation of the catheter is essential in in vivo navigation, and that the proposed rear view mirror interface to show non-visible obstacles is appropriate; in conclusion, the results proved the validity of the proposed solution to develop an intrinsically safe robotic system for navigation and intervention in a narrow and challenging environment such as the spinal subarachnoid space.


2019 ◽  
pp. 508-519
Author(s):  
Peter Hoskin

Chapter 22 discusses radiotherapy planning for metastatic disease, predominantly for patients with bone metastasis, spinal cord compression, and brain metastasis. The techniques for such treatments are specific to this indication rather than the primary tumour site.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Marco Manca ◽  
Elisabeth Glowatzki ◽  
Dale C. Roberts ◽  
Gene Y. Fridman ◽  
Felix P. Aplin

AbstractRecent studies have shown that ionic direct current (iDC) can modulate the vestibular system in-vivo, with potential benefits over conventional pulsed stimulation. In this study, the effects of iDC stimulation on vestibular nerve fiber firing rate was investigated using loose-patch nerve fiber recordings in the acutely excised mouse crista ampullaris of the semicircular canals. Cathodic and anodic iDC steps instantaneously reduced and increased afferent spike rate, with the polarity of this effect dependent on the position of the stimulating electrode. A sustained constant anodic or cathodic current resulted in an adaptation to the stimulus and a return to spontaneous spike rate. Post-adaptation spike rate responses to iDC steps were similar to pre-adaptation controls. At high intensities spike rate response sensitivities were modified by the presence of an adaptation step. Benefits previously observed in behavioral responses to iDC steps delivered after sustained current may be due to post-adaptation changes in afferent sensitivity. These results contribute to an understanding of peripheral spike rate relationships for iDC vestibular stimulation and validate an ex-vivo model for future investigation of cellular mechanisms. In conjunction with previous in-vivo studies, these data help to characterize iDC stimulation as a potential therapy to restore vestibular function after bilateral vestibulopathy.


2016 ◽  
Vol 57 (12) ◽  
pp. 1531-1539 ◽  
Author(s):  
Peng Zhao ◽  
Chao Kong ◽  
Xueming Chen ◽  
Hua Guan ◽  
Zhenshan Yu ◽  
...  

2018 ◽  
Vol 68 ◽  
pp. 78-89 ◽  
Author(s):  
Nicole L. Ramo ◽  
Snehal S. Shetye ◽  
Femke Streijger ◽  
Jae H.T. Lee ◽  
Kevin L. Troyer ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Giovanni Cirillo ◽  
Daniele De Luca ◽  
Michele Papa

Astrocytic Ca2+dynamics have been extensively studied inex vivomodels; however, the recent development of two-photon microscopy and astrocyte-specific labeling has allowed the study of Ca2+signaling in living central nervous system. Ca2+waves in astrocytes have been described in cultured cells and slice preparations, but evidence for astrocytic activation during sensory activity is lacking. There are currently few methods to image living spinal cord: breathing and heart-beating artifacts have impeded the widespread application of this technique. We here imaged the living spinal cord by two-photon microscopy in C57BL6/J mice. Through pressurized injection, we specifically loaded spinal astrocytes using the red fluorescent dye sulforhodamine 101 (SR101) and imaged astrocytic Ca2+levels with Oregon-Green BAPTA-1 (OGB). Then, we studied astrocytic Ca2+levels at rest and after right electrical hind paw stimulation. Sensory stimulation significantly increased astrocytic Ca2+levels within the superficial dorsal horn of the spinal cord compared to rest. In conclusion,in vivomorphofunctional imaging of living astrocytes in spinal cord revealed that astrocytes actively participate to sensory stimulation.


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