The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Patrick W Mantyh - One of the best experts on this subject based on the ideXlab platform.
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administration of a tropomyosin receptor kinase inhibitor attenuates sarcoma induced nerve sprouting neuroma formation and bone Cancer Pain
Molecular Pain, 2010Co-Authors: Joseph R Ghilardi, Juan Miguel Jimenezandrade, William G Mantyh, Aaron P Bloom, Katie T Freeman, Michael A. Kuskowski, Patrick W MantyhAbstract:Pain often accompanies Cancer and most current therapies for treating Cancer Pain have significant unwanted side effects. Targeting nerve growth factor (NGF) or its cognate receptor tropomyosin receptor kinase A (TrkA) has become an attractive target for attenuating chronic Pain. In the present report, we use a mouse model of bone Cancer Pain and examine whether oral administration of a selective small molecule Trk inhibitor (ARRY-470, which blocks TrkA, TrkB and TrkC kinase activity at low nm concentrations) has a significant effect on Cancer-induced Pain behaviors, tumor-induced remodeling of sensory nerve fibers, tumor growth and tumor-induced bone remodeling. Early/sustained (initiated day 6 post Cancer cell injection), but not late/acute (initiated day 18 post Cancer cell injection) administration of ARRY-470 markedly attenuated bone Cancer Pain and significantly blocked the ectopic sprouting of sensory nerve fibers and the formation of neuroma-like structures in the tumor bearing bone, but did not have a significant effect on tumor growth or bone remodeling. These data suggest that, like therapies that target the Cancer itself, the earlier that the blockade of TrkA occurs, the more effective the control of Cancer Pain and the tumor-induced remodeling of sensory nerve fibers. Developing targeted therapies that relieve Cancer Pain without the side effects of current analgesics has the potential to significantly improve the quality of life and functional status of Cancer patients.
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blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage Cancer Pain
Neuroscience, 2010Co-Authors: William G Mantyh, Juan Miguel Jimenezandrade, Joseph R Ghilardi, James I Stake, Aaron P Bloom, Magdalena J Kaczmarska, Reid N Taylor, Katie T Freeman, Michael A. Kuskowski, Patrick W MantyhAbstract:For many patients, Pain is the first sign of Cancer and, while Pain can be present at any time, the frequency and intensity of Pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage Cancer will experience significant Cancer-induced Pain. One major unanswered question is why Cancer Pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a mouse model of bone Cancer Pain to demonstrate that as tumor growth progresses within bone, tropomyosin receptor kinase A (TrkA)-expressing sensory and sympathetic nerve fibers undergo profuse sprouting and form neuroma-like structures. To address what is driving the pathological nerve reorganization we administered an antibody to nerve growth factor (anti-NGF). Early sustained administration of anti-NGF, whose cognate receptor is TrkA, blocks the pathological sprouting of sensory and sympathetic nerve fibers, the formation of neuroma-like structures, and inhibits the development of Cancer Pain. These results suggest that Cancer cells and their associated stromal cells release nerve growth factor (NGF), which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving Cancer Pain. Similar to therapies that target the Cancer itself, the data presented here suggest that, the earlier therapies blocking this pathological nerve remodeling are initiated, the more effective the control of Cancer Pain.
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Cancer Pain and its impact on diagnosis survival and quality of life
Nature Reviews Neuroscience, 2006Co-Authors: Patrick W MantyhAbstract:Cancer Pain significantly affects the diagnosis, quality of life and survival of patients with Cancer. During the past decade, preclinical and clinical data has begun to provide insight into the mechanisms that drive and mask Cancer Pain and the mechanisms by which anti-neoplastic agents induce peripheral neuropathy. Developing a mechanism-based understanding and mechanism-based therapies to treat Cancer-associated Pain and sensory neuropathy, and incorporating these into mainstream Cancer research and therapy, will be crucial to improving the quality of life and survival of patients with Cancer.
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molecular mechanisms of Cancer Pain
Nature Reviews Cancer, 2002Co-Authors: Patrick W Mantyh, Denis R. Clohisy, M Koltzenburg, Steve P HuntAbstract:Pain is the most disruptive influence on the quality of life of Cancer patients. Although significant advances are being made in Cancer treatment and diagnosis, the basic neurobiology of Cancer Pain is poorly understood. New insights into these mechanisms are now arising from animal models, and have the potential to fundamentally change the way that Cancer Pain is controlled.
Yanqing Wang - One of the best experts on this subject based on the ideXlab platform.
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stage dependent analgesia of electro acupuncture in a mouse model of cutaneous Cancer Pain
European Journal of Pain, 2006Co-Authors: Qiliang Maoying, Ke Mi Cui, Qiong Liu, Zhiqiang Dong, Wei Wang, Jun Wang, Hong Sha, Yanqing WangAbstract:Acupuncture is one of the most effective alternative medical treatments in Pain management with the advantages of simple application, low cost and minimal side effects. However its scientific evidence and laws of action are not very clear in Cancer Pain relieving. The aim of this study was to examine the immediate and therapeutic anti-hyperalgesic effect of electro-acupuncture (EA) on a mouse model of cutaneous Cancer Pain. B16-BL6 melanoma cells were inoculated into the plantar region of unilateral hind paw and the thermal hyperalgesia was measured by using radiant heat test and hot plate test. C57BL/6 mice showed moderate and marked hyperalgesia during days 8-12 and from day 14 after the orthotopic inoculation of B16-BL6 melanoma cells into the hind paw. Single EA on day 8 after inoculation showed significant analgesic effect immediately after the treatment, the analgesic effect reached its maximum within 15-30min and declined to its minimum at 50min after EA treatment. Single EA treatment on day 20 showed no significant analgesic effect; Repeated EA treatments (started from day 8, once every other day) showed therapeutic analgesic effect, while it showed no therapeutic effect when started from day 16, a relatively late stage of this Cancer Pain model. The results demonstrated that EA had anti-hyperalgesic effect on early stage of cutaneous Cancer Pain but not on late stage. These results indicated a tight correlation of EA anti-hyperalgesic effects with the time window of Cancer Pain.
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a rat model of bone Cancer Pain induced by intra tibia inoculation of walker 256 mammary gland carcinoma cells
Biochemical and Biophysical Research Communications, 2006Co-Authors: Qiliang Maoying, Yu-qiu Zhang, Zhiqiang Dong, Jun Wang, Jun Zhao, Minfen Yan, Yanqing WangAbstract:This study described a modified rat model of bone Cancer Pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory Pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory Pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Abeta fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The Pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of 'mirror image' Pain in bone Cancer Pain. In summary, the present study provided a useful and easily established rat model of bone Cancer Pain which will contribute to further study of the mechanisms underlying Cancer Pain.
Y U Weifeng - One of the best experts on this subject based on the ideXlab platform.
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a rat model of tibia Cancer Pain produced by walker 256 mammary gland carcinoma cells
Chinese Journal of Cancer, 2008Co-Authors: Y U WeifengAbstract:Objective:To establish a tibial Cancer Pain model with Walker 256 mammary gland carcinoma cell line (CCL), so as to provide a useful tool for further study of the mechanisms underlying Cancer Pain and its treatment. Methods: Walker 256 mammary gland carcinoma cells were injected into the cavum abdominis of infant rats to prepare ascitic tumor fluid. A total of 15 μl ascitic tumor fluid was injected into the cavum medullare ossium of left tibia in adult SD rats to establish tibial Cancer Pain model. Thermoinactivated cells were injected into the adult SD rats (sham group); normal SD rats served as normal control group. One to 4 weeks after injection, walk-associated Pain, radiation heat-associated Pain threshold (paw withdrawal latency, PWL) and mechanical Pain threshold(pwa withdrawal threshold, PWT) were all observed. And the bone damage in the models with Pain behavior obviously changed was monitored by radiograph analysis. Results: Successful tumor forming was achieved in 67.3% of rats. Fifteen days after model establishment, walk-associated Pain score of the model group was obviously higher than that of the sham group and normal control group(P0.01). The PWL and PWT of the injected tibia in the model group were obviously lower than those of the normal control group and sham group at 21 d and 18 d after injection (P0.01); meanwhile, they were also obviously lower than those of the hind limbs of the contralateral side in the model group (P0.05). Radiograph data showed that the injected tibias of models with obviously changed Pain behavior was obviously damaged. Conclusion: The rats model of tibial Cancer Pain, similar to the human bone Cancer Pain, can be successfully established by Walker 256 mammary gland cells.
Manfred Raber - One of the best experts on this subject based on the ideXlab platform.
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long term treatment of Cancer Pain with transdermal fentanyl
Journal of Pain and Symptom Management, 1998Co-Authors: B Donner, Michael Strumpf, Michael Zenz, Manfred RaberAbstract:Abstract The long-term therapy of 51 patients using transdermal fentanyl was evaluated. The transdermal therapy was performed for 158 days (range, 15–855 days). The need for increasing dosages of transdermal fentanyl was caused by the progression of the underlying Cancer disease (mean initial dose, 69.5 μ g fentanyl/hr; mean final dose, 167.7 μ g fentanyl/hr). The transdermal system was changed every third day. Application intervals had to be shortened in 23.5% of the patients. Pain reduction was good throughout the study. Severe side effects did not occur. Constipation and the need for laxatives occurred less frequently than with previously administered oral morphine. Skin tolerance of the transdermal system was good. The treatment of Cancer Pain with transdermal fentanyl can be performed as a long-term therapy and result in good Pain relief. Considering its specific pharmacokinetic properties, it is an alternative medication on step III of the World Health Organization's guidelines for Cancer Pain management.
Martin P Uitendaal - One of the best experts on this subject based on the ideXlab platform.
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transdermal fentanyl in opioid naive Cancer Pain patients an open trial using transdermal fentanyl for the treatment of chronic Cancer Pain in opioid naive patients and a group using codeine
Journal of Pain and Symptom Management, 2000Co-Authors: Ans P E Vielvoyekerkmeer, Carlien Mattern, Martin P UitendaalAbstract:Abstract To treat Cancer Pain, physicians often decide to jump directly from step 1 of the World Health Organization (WHO) analgesic ladder to step 3. The use of transdermal fentanyl in patients with Cancer Pain who had either used no opioid before, or only codeine, is evaluated in the present trial. Both opioid-naive ( N = 14) and codeine-using ( N = 14) patients started with transdermal fentanyl in the lowest available delivery rate (25 μg/hr). Immediate-release oral morphine was present as "rescue" medication. Transdermal fentanyl provided good to excellent Pain relief in the majority (68 % ) of these patients. During the study, 5 patients continued with 25 μg/hr, and the others used a higher dose. Clinically relevant respiratory depression was not observed. The common side effects of opioids were found; constipation was mentioned by 3 patients (11 % ). Transdermal fentanyl appeared a safe analgesic in these opioid-naive Cancer Pain patients. In this study, WHO step 2 could be skipped without untoward complications.
