Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facili...Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats’ RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of proinflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.展开更多
Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatmen...Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.展开更多
Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similari...Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.展开更多
Background： Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain （CIBP）. In the present stu...Background： Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain （CIBP）. In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods： A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III （MDL28170, 1 mg/kg） on mechanical withdrawal threshold （MWT） of bilateral hind paws was examined on postoperative days （PODs） 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor＇s effect on tumor bone tartrate-resistant acid phosphatase （TRAP） stain and radiology was also carefully investigated. Results： Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 （P 〈 0.05）. TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group （P 〈 0.05）. However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions： Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.展开更多
Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy...Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.展开更多
[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain sympt...[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain symptoms of osteoporosis.[Methods]Randomized controlled trials(RCTs)of salmon calcitonin in the treatment of osteoporosis from January 2000 to March 2015 were collected by searching Chinese Biomechanics Literature Database(SinoMed,CBM),China National Knowledge Infrastructure(CNKI),VIP and Wanfang Database.The relevant data of bone pain degree and bone mineral density were extracted to evaluate the methodological quality.Meta-analysis was performed using RevMan 5.1 software.A total of 13 randomized controlled trials involving 1683 patients were included,including 862 patients in the observation group and 821 patients in the control group.[Results]Meta-analysis showed that salmon calcitonin combined with calcium was better than the control group in improving bone pain symptoms in osteoporosis patients,and the difference was statistically significant[RR=1.84,95%CI(1.56,2.18)].[Conclusions]The salmon calcitonin can significantly improve the bone pain symptoms of the osteoporosis patients,and has no serious adverse reaction.However,due to the small number of studies included in this systematic review and the small sample size,it still needs to be confirmed by high-quality,large sample,multi-center randomized controlled trials.展开更多
BACKGROUND Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients,and fish bones are the objects that most commonly lead to bowel perforation. When it does occur,the termin...BACKGROUND Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients,and fish bones are the objects that most commonly lead to bowel perforation. When it does occur,the terminal ileum is the most common site of perforation,followed by the duodenal C-loop. However,involvement of the pancreas is very rare. Because clinical symptoms are nonspecific and gastrointestinal perforation may present as only odynophagia or abdominal pain,a definite preoperative diagnosis and clinical intervention may be delayed.CASE SUMMARY We report the case of a 32-year-old man who presented to our hospital because of abdominal pain that had worsened over 5 d. He had no significant past history except that he had eaten fish 1 wk previously. Upper endoscopy revealed an irregular submucosal tumor on the front wall of the gastric antrum. Endoscopic ultrasonography and computed tomography showed a fish bone penetrating the gastric antrum and migratingin to the neck of the pancreas. The patient underwent laparoscopic surgery and had no complications one week after the operation.CONCLUSION A recent history of foreign body ingestion and imaging examinations are helpful for diagnosis of unexplained abdominal pain caused by foreign bodies.展开更多
Purpose: The Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of Vertebroplasty, demonstrated similar improvements in pain between blinded Vertebroplasty and sha...Purpose: The Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of Vertebroplasty, demonstrated similar improvements in pain between blinded Vertebroplasty and sham-Vertebroplasty groups. The result from the RCT study suggested that the observed efficacy of the Vertebroplasty procedure, instead of representing the cement-mediated reduction in pain, may relate to the vertebral bone drilling per se. The aim of this study was to demonstrate the effectiveness of pain relief of vertebral bone drilling at the site of painful osteoporotic vertebral compression fractures in the acute phase. Materials and Methods: Twenty-six patients with painful osteoporotic compression fractures underwent the vertebral bone drilling. We assessed primary outcome measures in the NRS pain score and RDQ score at day 0 and 3 following the drilling. Comparisons were made by using Wilcoxon signed rank test. Results: The mean baseline NRS and RDQ score, and the mean NRS and RDQ score at day 3 were 7.3 ± 1.2, 15.7 ± 4.2, 4.6 ± 1.4, 7.3 ± 2.2, respectively. Among the patients, we detected significant improvements in NRS pain score and RDQ score at day 3 following the drilling compared with day 0 (P < 0.001). Conclusion: Vertebral bone drilling at the site of painful vertebral compression fractures alleviated the intractable pain due to osteoporotic vertebral compression fractures.展开更多
<strong><em>Background. </em></strong>The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer m...<strong><em>Background. </em></strong>The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. <strong><em>Methods.</em></strong> By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected.<strong><em> Results. </em></strong>Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p < 0.05), and the cold pain and spontaneous pain scores increased significantly (p < 0.05). After group study, the expression of c-fos in the cancer pain model group was significantly higher than that in the normal control group (p < 0.05), and with the increase of curcumin dose, the expression of c-fos in the high dose group was significantly lower than that in the solvent model group (p < 0.05). The expression of RANK, NF-κB, TNF-α was higher than that of the normal control group and decreased gradually with the increase of curcumin dose, among which the expression of high dose group was significantly lower than that of solvent group (p < 0.05). RANK, NF-κB, TNF-α protein expression was higher than that of normal control group and gradually decreased with the increase of curcumin dose. The levels of Cox2, IL-6, leukotriene and PGE2 in serum decreased with the increase of curcumin dose, and the high dose group decreased significantly (p < 0.05). <em><strong>Conclusions. </strong></em>On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.展开更多
Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the ...Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.展开更多
In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1...In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1） have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1（p JNK1） and p JNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective p JNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the p JNK/CXCL1 pathway may provide a new choice for treatment of CIBP.展开更多
Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in...Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in 12 cases was significantly relieved.14 cases acquired relif.Total effective rate was 83.9%.Activity ability was improved by 80.6%.No apparent toxicological and adverse effects as well as fever and cold symptoms were observed.Conclusion Aredia is a kind of ideal drugs for treatment of pain caused by malignant metastatic bone tumors.It is convenient in use and could be endured by patients.展开更多
The aim of this investigation was to analyze the associations of TMJ pain/discomfort and bone characteristics on the activities of daily living in a population based study. Methods: The study included 95 randomly sele...The aim of this investigation was to analyze the associations of TMJ pain/discomfort and bone characteristics on the activities of daily living in a population based study. Methods: The study included 95 randomly selected participants. The impact of temporomandibular joint pain/discomfort on the daily activeties was assessed by using the daily living scale by List and Helkimo (1995). The levels of serum type I collagen telopeptide fragments (P1NP), C-telopeptide crosslaps of type I collagen (CTX-1), and vitamin D (25 (OH) D) were analysed. The Mann-Whitney U-test, Spearman rank correlation coefficent (rs) were used for statistical analyses. Results: Activities of daily living were influenced by temporomandibular joint pain/discomfort to varying degrees. The degree of pain/discomfort during eating was correlated with the level of C-telopeptide crosslaps of type I collagen (p = 0.02) and type 1 collagen telopeptide fragments (p = 0.04). The females in the study had significantly lower vitamin D levels compared to males (p = 0.04). Conclusions: This population based study indicates that TMJ pain/discomfort exerts a significant negative influence on activities of daily living and is related to the biochemical markers of bone turnover and 25 (OH) D level. Several functions of daily activities such as social life, exercising and eating are the most disturbed.展开更多
Objective:To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone.Methods:52 patients with metastatic tumor of bone were randomly divided into two groups.The zoledronic a...Objective:To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone.Methods:52 patients with metastatic tumor of bone were randomly divided into two groups.The zoledronic acid group received 4 mg zoledronic acid infusion for 30 minutes and the control group received 90 mg pamidronate infusion for 6 hours. Results:The effective rates in zoledronic acid group and control group were 73.08%and 69.23%respectively.No significant difference was observed between the two groups.The median pain relief onset at days 5 and 7,respectively,and no significant difference was observed.The ECOG scores on the 7th day after medication:the differences in the zoledronic acid group before and after medication and between the two groups were both significant(P<0.001 and P=0.0448).The adverse reac- tion was no significant difference between the two groups.Conclusion:Zoledronic acid is efficient and safe in the treatment of pain caused by metastatic tumor of bone and it has low adverse reaction rate and convenient shorter using time.展开更多
BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-...BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.展开更多
Objective: To compare 3 local field radiation therapies for bone metastases to determine the strategy producing the best results. Methods: Among 104 patients with bone metastases, 30 patients were given 8 Gy in single...Objective: To compare 3 local field radiation therapies for bone metastases to determine the strategy producing the best results. Methods: Among 104 patients with bone metastases, 30 patients were given 8 Gy in single fraction, 31 given 20 Gy in 5 fractions, 43 given 40 Gy in 20 fractions. Results and Conclusion: The method of 40 Gy in 20 fractions had a higher pain relief rate and a lower pain relapse rate, suggesting that large-dose fractioned treatment regimen is more appropriate for patients with bone metastasis.展开更多
Background:Growing pain (GP) is the most common form of nonspecific, recurrent leg pain in children aged 4 - 12 years. The exact etiology of GP is not known. However, some studies have found an association between vit...Background:Growing pain (GP) is the most common form of nonspecific, recurrent leg pain in children aged 4 - 12 years. The exact etiology of GP is not known. However, some studies have found an association between vitamin D and Bone Mineral Status (BMD) status with GP in their study. Objectives: To assess the serum level of vitamin D, and BMD and to determine their association with growing pain in children. Methods: This cross-sectional analytical study was conducted in the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). Sixty children between the age of 6 - 12 years were included in the study from March 2020 to August 2021. Children who fulfilled the Evans criteria of GP were enrolled as cases and thirty age and sex matched healthy children were recruited as the control in the study. Informed written consent was obtained from patients and parents. Serum 25-hydroxy-vitamin-D levels and BMD were performed among cases and controls and subsequently compared to see their association in growing pain. A preformed semi-structured questionnaire was completed for each participant which included socio-demographic, clinical and laboratory characteristics. Appropriate statistical tests were applied for data analysis and performed by SPSS version 22. A p-value less than 0.05 was considered as significant at a 95% confidence interval. Results: In this study, 96.7% of growing pain patients had hypovitaminosis D and among them,<span style="font-family: "> the majority (86.7%) was vitamin D deficient. There was a significant association between vitamin D with GP compared to healthy control. BMD was significantly lower in the lumbar vertebra (L1 -<span style="font-family: "> L4) and femoral neck region (both right and left) among GP children compared to the control group. Conclusion: From this study, it may be concluded that the majority of children with GP had hypovitaminosis D and low BMD status compared to the control. Vitamin D deficiency and low BMD status were significantly associated with children with growing pain. Institutional Review Board (I.R.B.) Clearance Certificate (NO. BSMMU/2020/4503 Date: 15/03/2020) was provided from the office of the Registrar, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.展开更多
Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone canc...Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.展开更多
Objective:To study the effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain.Methods:Walker256 cells were passaged in ascites and injected into the tibia of female W...Objective:To study the effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain.Methods:Walker256 cells were passaged in ascites and injected into the tibia of female Wistar rats to prepare the bone cancer pain model.On the 14th day after model establishment,60 rats were randomly divided into model group,sham-operated group,Yishen Qutong granula low,middle,high dose group and tramadol hydrochloride positive control group.After continuous administration for 14 days,the mechanical pain threshold,thermal threshold and weight-bearing difference of both hind limbs were observed.Results:Compared with the model group,Yishen Qutong groups increased the mechanical pain threshold,thermal pain threshold and reduced the weight difference of both hind limbs(P<0.05).Compared with the positive drug group,there was no significant difference in increasing the mechanical pain threshold and thermal pain threshold of rats in the medium dose group of Yishen Qutong(P>0.05),and Yishen Qutong granula significantly reduced the weight-bearing difference of hind limbs in all groups(P<0.05).Conclusion:Yishen Qutong granula can relieve pain sensitization and alleviate bone damage in rats with bone cancer pain.展开更多
As quality and cost effectiveness become essential in clinical practice,an evidencebased evaluation of the utility of imaging orders becomes an important consideration for radiology’s value in patient care.We report ...As quality and cost effectiveness become essential in clinical practice,an evidencebased evaluation of the utility of imaging orders becomes an important consideration for radiology’s value in patient care.We report an institutional quality improvement project including a retrospective review of utility of sacrum magnetic resonance(MR)imaging for low back pain at our institution over a four-year period and follow-up results after physician education intervention.Sacral MR imaging for low back pain and tailbone pain were only positive for major findings in 2/98(2%)cases,and no major changes in patient management related to imaging findings occurred over this period,resulting in almost$500000 cost without significant patient benefit.We distributed these results to the Family Medicine department and clinics that frequently placed this order.An approximately 83%drop in ordering rate occurred over the ensuing 3 mo follow-up period.Sacrum MR imaging for low back pain and tail bone pain has not been a cost-effective diagnostic tool at our institution.Physician education was a useful tool in reducing overutilization of this study,with a remarkable drop in such studies after sharing these findings with primary care physicians at the institution.In conclusion,sacrum MR imaging rarely elucidates the cause of low back/tail pain diagnosed in a primary care setting and is even less likely to result in major changes in management.The practice can be adopted in other institutions for the benefit of their patients and improve cost efficiency.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.30901396,No.81070890,No.30872441and No.81171259)
文摘Descending nociceptive modulation from the supraspinal structures plays an important role in cancer-induced bone pain (CIBP). Rostral ventromedial medulla (RVM) is a critical component of descending nociceptive facilitation circuitry, but so far the mechanisms are poorly known. In this study, we investigated the role of RVM glial activation in the descending nociceptive facilitation circuitry in a CIBP rat model. CIBP rats showed significant activation of microglia and astrocytes, and also up-regulation of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) and pro-inflammatory mediators released by glial cells (IL-1β, IL-6, TNF-α and brain-derived neurotrophic factor) in the RVM. Stereotaxic microinjection of the glial inhibitors (minocycline and fluorocitrate) into CIBP rats’ RVM could reverse the glial activation and significantly attenuate mechanical allodynia in a time-dependent manner. RVM microinjection of p38 MAPK inhibitor (SB203580) abolished the activation of microglia, reversed the associated up-regulation of proinflammatory mediators and significantly attenuated mechanical allodynia. Taken together, these results suggest that RVM glial activation is involved in the pathogenesis of CIBP. RVM microglial p38 MAPK signaling pathway is activated and leads to the release of downstream pro-inflammatory mediators, which contribute to the descending facilitation of CIBP.
基金financially supported by the National Natural Science Foundation of China(No.82001189)The Project Tackling of Key Scientific and Technical Problems of Henan Provine(No.232102311163).
文摘Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.
基金supported by the Zhongshan-Fudan Joint Innovation Center,Zhongshan,Guangdong Province,China(528437)the National Natural Science Foundation of China(82271258,82271248,82204830,81971056)+1 种基金Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis.CIBP constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic pain.At present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be achieved.Hence,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic drugs.Herein,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root ganglion.The nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to CIBP.The peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.
基金This study was funded by Beijing Natural Science Foundation
文摘Background： Calpain, a calcium-dependent cysteine protease, has been demonstrated to regulate osteoclastogenesis, which is considered one of the major reasons for cancer-induced bone pain （CIBP）. In the present study, calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity. Methods： A rat CIBP model was established with intratibial injection of Walker 256 cells. Then, the efficacy of intraperitoneal administered calpain inhibitor III （MDL28170, 1 mg/kg） on mechanical withdrawal threshold （MWT） of bilateral hind paws was examined on postoperative days （PODs） 2, 5, 8, 11, and 14. On POD 14, the calpain inhibitor＇s effect on tumor bone tartrate-resistant acid phosphatase （TRAP） stain and radiology was also carefully investigated. Results： Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5, 8, and 11 （P 〈 0.05）. TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group （P 〈 0.05）. However, bone resorption and destruction measured by radiographs showed no difference between the two groups. Conclusions： Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model. It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis. Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.
文摘Bone metastases(BM)are a common complication in advanced cancer patients,significantly contributing to morbidity and mortality due to their ability to cause pain,fractures,and spinal cord compression.Radiation therapy(RT)is vital in managing these complications by targeting metastatic lesions to ease pain,improve mobility,and reduce the risk of skeletal-related events such as fractures.Evidence supports the effectiveness of RT in pain relief,showing its ability to provide significant palliation and lessen the need for opioid painkillers,thereby enhancing the overall quality of life(QoL)for patients with BM.However,optimizing RT outcomes involves considerations such as the choice of radiation technique,dose fractionation schedules,and the integration of supportive care measures to mitigate treatment-related side effects like fatigue and skin reactions.These factors highlight the importance of personalized treatment planning tailored to individual patient needs and tumor characteristics.This mini-review aims to provide comprehensive insights into the multifaceted impacts of RT on pain management and QoL enhancement in BM patients,with implications for refining clinical practices and advancing patient care through the synthesis of findings from various studies.
文摘[Objectives]To systematically evaluate the efficacy and safety of salmon calcitonin in the treatment of osteoporosis,and to provide reference for clinical salmon calcitonin treatment and improvement of bone pain symptoms of osteoporosis.[Methods]Randomized controlled trials(RCTs)of salmon calcitonin in the treatment of osteoporosis from January 2000 to March 2015 were collected by searching Chinese Biomechanics Literature Database(SinoMed,CBM),China National Knowledge Infrastructure(CNKI),VIP and Wanfang Database.The relevant data of bone pain degree and bone mineral density were extracted to evaluate the methodological quality.Meta-analysis was performed using RevMan 5.1 software.A total of 13 randomized controlled trials involving 1683 patients were included,including 862 patients in the observation group and 821 patients in the control group.[Results]Meta-analysis showed that salmon calcitonin combined with calcium was better than the control group in improving bone pain symptoms in osteoporosis patients,and the difference was statistically significant[RR=1.84,95%CI(1.56,2.18)].[Conclusions]The salmon calcitonin can significantly improve the bone pain symptoms of the osteoporosis patients,and has no serious adverse reaction.However,due to the small number of studies included in this systematic review and the small sample size,it still needs to be confirmed by high-quality,large sample,multi-center randomized controlled trials.
文摘BACKGROUND Ingestion of foreign bodies results in gastrointestinal perforation in approximately 1% of patients,and fish bones are the objects that most commonly lead to bowel perforation. When it does occur,the terminal ileum is the most common site of perforation,followed by the duodenal C-loop. However,involvement of the pancreas is very rare. Because clinical symptoms are nonspecific and gastrointestinal perforation may present as only odynophagia or abdominal pain,a definite preoperative diagnosis and clinical intervention may be delayed.CASE SUMMARY We report the case of a 32-year-old man who presented to our hospital because of abdominal pain that had worsened over 5 d. He had no significant past history except that he had eaten fish 1 wk previously. Upper endoscopy revealed an irregular submucosal tumor on the front wall of the gastric antrum. Endoscopic ultrasonography and computed tomography showed a fish bone penetrating the gastric antrum and migratingin to the neck of the pancreas. The patient underwent laparoscopic surgery and had no complications one week after the operation.CONCLUSION A recent history of foreign body ingestion and imaging examinations are helpful for diagnosis of unexplained abdominal pain caused by foreign bodies.
文摘Purpose: The Investigational Vertebroplasty Efficacy and Safety Trial (INVEST), a randomized blinded controlled study of Vertebroplasty, demonstrated similar improvements in pain between blinded Vertebroplasty and sham-Vertebroplasty groups. The result from the RCT study suggested that the observed efficacy of the Vertebroplasty procedure, instead of representing the cement-mediated reduction in pain, may relate to the vertebral bone drilling per se. The aim of this study was to demonstrate the effectiveness of pain relief of vertebral bone drilling at the site of painful osteoporotic vertebral compression fractures in the acute phase. Materials and Methods: Twenty-six patients with painful osteoporotic compression fractures underwent the vertebral bone drilling. We assessed primary outcome measures in the NRS pain score and RDQ score at day 0 and 3 following the drilling. Comparisons were made by using Wilcoxon signed rank test. Results: The mean baseline NRS and RDQ score, and the mean NRS and RDQ score at day 3 were 7.3 ± 1.2, 15.7 ± 4.2, 4.6 ± 1.4, 7.3 ± 2.2, respectively. Among the patients, we detected significant improvements in NRS pain score and RDQ score at day 3 following the drilling compared with day 0 (P < 0.001). Conclusion: Vertebral bone drilling at the site of painful vertebral compression fractures alleviated the intractable pain due to osteoporotic vertebral compression fractures.
文摘<strong><em>Background. </em></strong>The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. <strong><em>Methods.</em></strong> By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected.<strong><em> Results. </em></strong>Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p < 0.05), and the cold pain and spontaneous pain scores increased significantly (p < 0.05). After group study, the expression of c-fos in the cancer pain model group was significantly higher than that in the normal control group (p < 0.05), and with the increase of curcumin dose, the expression of c-fos in the high dose group was significantly lower than that in the solvent model group (p < 0.05). The expression of RANK, NF-κB, TNF-α was higher than that of the normal control group and decreased gradually with the increase of curcumin dose, among which the expression of high dose group was significantly lower than that of solvent group (p < 0.05). RANK, NF-κB, TNF-α protein expression was higher than that of normal control group and gradually decreased with the increase of curcumin dose. The levels of Cox2, IL-6, leukotriene and PGE2 in serum decreased with the increase of curcumin dose, and the high dose group decreased significantly (p < 0.05). <em><strong>Conclusions. </strong></em>On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.
基金supported by the National Natural Science Foundation of China,Nos. 82071556 (to WM), 81873793 (to WM), 82001198 (to YQZ), 82101310 (to DQL)the National Key Research and Development Program of China,No. 2020YFC2005300 (to WM)。
文摘Nitric oxide(NO)/cyclic guanosine 3′,5′-monophosphate(cGMP) signaling has been shown to act as a mediator involved in pain transmission and processing. In this review, we summarize and discuss the mechanisms of the NO/cGMP signaling pathway involved in chronic pain, including neuropathic pain, bone cancer pain, inflammatory pain, and morphine tolerance. The main process in the NO/cGMP signaling pathway in cells involves NO activating soluble guanylate cyclase, which leads to subsequent production of cGMP. cGMP then activates cGMP-dependent protein kinase(PKG), resulting in the activation of multiple targets such as the opening of ATP-sensitive K+ channels. The activation of NO/cGMP signaling in the spinal cord evidently induces upregulation of downstream molecules, as well as reactive astrogliosis and microglial polarization which participate in the process of chronic pain. In dorsal root ganglion neurons, natriuretic peptide binds to particulate guanylyl cyclase, generating and further activating the cGMP/PKG pathway, and it also contributes to the development of chronic pain. Upregulation of multiple receptors is involved in activation of the NO/cGMP signaling pathway in various pain models. Notably the NO/cGMP signaling pathway induces expression of downstream effectors, exerting both algesic and analgesic effects in neuropathic pain and inflammatory pain. These findings suggest that activation of NO/cGMP signaling plays a constituent role in the development of chronic pain, and this signaling pathway with dual effects is an interesting and promising target for chronic pain therapy.
基金supported by the National Natural Science Foundation of China(No.81172150)
文摘In patients with advanced cancer, cancer-induced bone pain（CIBP） is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase（JNK） and chemokine（C-X-C motif） ligand 1（CXCL1） have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1（p JNK1） and p JNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective p JNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the p JNK/CXCL1 pathway may provide a new choice for treatment of CIBP.
文摘Objective To study therapeutic efficacy of Aredia in treating malignant metastatic bone tumors. Method 60～90 mg Aredia was administrated iv in 31 cases with malignant metastatic tumors,once each week. Results Pain in 12 cases was significantly relieved.14 cases acquired relif.Total effective rate was 83.9%.Activity ability was improved by 80.6%.No apparent toxicological and adverse effects as well as fever and cold symptoms were observed.Conclusion Aredia is a kind of ideal drugs for treatment of pain caused by malignant metastatic bone tumors.It is convenient in use and could be endured by patients.
文摘The aim of this investigation was to analyze the associations of TMJ pain/discomfort and bone characteristics on the activities of daily living in a population based study. Methods: The study included 95 randomly selected participants. The impact of temporomandibular joint pain/discomfort on the daily activeties was assessed by using the daily living scale by List and Helkimo (1995). The levels of serum type I collagen telopeptide fragments (P1NP), C-telopeptide crosslaps of type I collagen (CTX-1), and vitamin D (25 (OH) D) were analysed. The Mann-Whitney U-test, Spearman rank correlation coefficent (rs) were used for statistical analyses. Results: Activities of daily living were influenced by temporomandibular joint pain/discomfort to varying degrees. The degree of pain/discomfort during eating was correlated with the level of C-telopeptide crosslaps of type I collagen (p = 0.02) and type 1 collagen telopeptide fragments (p = 0.04). The females in the study had significantly lower vitamin D levels compared to males (p = 0.04). Conclusions: This population based study indicates that TMJ pain/discomfort exerts a significant negative influence on activities of daily living and is related to the biochemical markers of bone turnover and 25 (OH) D level. Several functions of daily activities such as social life, exercising and eating are the most disturbed.
文摘Objective:To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone.Methods:52 patients with metastatic tumor of bone were randomly divided into two groups.The zoledronic acid group received 4 mg zoledronic acid infusion for 30 minutes and the control group received 90 mg pamidronate infusion for 6 hours. Results:The effective rates in zoledronic acid group and control group were 73.08%and 69.23%respectively.No significant difference was observed between the two groups.The median pain relief onset at days 5 and 7,respectively,and no significant difference was observed.The ECOG scores on the 7th day after medication:the differences in the zoledronic acid group before and after medication and between the two groups were both significant(P<0.001 and P=0.0448).The adverse reac- tion was no significant difference between the two groups.Conclusion:Zoledronic acid is efficient and safe in the treatment of pain caused by metastatic tumor of bone and it has low adverse reaction rate and convenient shorter using time.
基金This study was approved by the Institutional Review Board of Samsung Medical Center(approval number:2020-09-027-001).
文摘BACKGROUND Osteomalacia(OM)is frequently confused with various musculoskeletal or other rheumatic diseases,especially in patients with adult-onset widespread musculoskeletal pain because of its low prevalence and non-specific manifestations.AIM To facilitate the early diagnosis and etiology-specific treatment of adult-onset hypophosphatemic OM.METHODS A retrospective review of medical records was performed to screen adult patients who visited a physiatry locomotive medicine clinic(spine and musculoskeletal pain clinic)primarily presenting with widespread musculoskeletal pain at a single tertiary hospital between January 2011 and December 2019.We enrolled patients with hypophosphatemia,high serum bone-specific alkaline phosphatase levels,and at least one imaging finding suggestive of OM.RESULTS Eight patients with adult-onset hypophosphatemic OM were included.The back was the most common site of pain.Proximal dominant symmetric muscle weakness was observed in more than half of the patients.Bone scintigraphy was the most useful imaging modality for diagnosing OM because radiotracer uptake in OM showed characteristic patterns.Six patients were diagnosed with adefovir(ADV)-induced Fanconi syndrome,and the other two patients were diagnosed with tumor-induced OM and light-chain nephropathy,respectively.After phosphorus and vitamin D supplementation and treatment for the underlying etiologies,improvements in pain,muscle strength,and gait were observed in all patients.CONCLUSION Mechanical pain characteristics,hypophosphatemia,and distinctive bone scintigraphy patterns are the initial diagnostic indicators of adult-onset hypophosphatemic OM.ADV-induced Fanconi syndrome is the most common etiology of hypophosphatemic OM in hepatitis B virus-endemic countries.
文摘Objective: To compare 3 local field radiation therapies for bone metastases to determine the strategy producing the best results. Methods: Among 104 patients with bone metastases, 30 patients were given 8 Gy in single fraction, 31 given 20 Gy in 5 fractions, 43 given 40 Gy in 20 fractions. Results and Conclusion: The method of 40 Gy in 20 fractions had a higher pain relief rate and a lower pain relapse rate, suggesting that large-dose fractioned treatment regimen is more appropriate for patients with bone metastasis.
文摘Background:Growing pain (GP) is the most common form of nonspecific, recurrent leg pain in children aged 4 - 12 years. The exact etiology of GP is not known. However, some studies have found an association between vitamin D and Bone Mineral Status (BMD) status with GP in their study. Objectives: To assess the serum level of vitamin D, and BMD and to determine their association with growing pain in children. Methods: This cross-sectional analytical study was conducted in the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). Sixty children between the age of 6 - 12 years were included in the study from March 2020 to August 2021. Children who fulfilled the Evans criteria of GP were enrolled as cases and thirty age and sex matched healthy children were recruited as the control in the study. Informed written consent was obtained from patients and parents. Serum 25-hydroxy-vitamin-D levels and BMD were performed among cases and controls and subsequently compared to see their association in growing pain. A preformed semi-structured questionnaire was completed for each participant which included socio-demographic, clinical and laboratory characteristics. Appropriate statistical tests were applied for data analysis and performed by SPSS version 22. A p-value less than 0.05 was considered as significant at a 95% confidence interval. Results: In this study, 96.7% of growing pain patients had hypovitaminosis D and among them,<span style="font-family: "> the majority (86.7%) was vitamin D deficient. There was a significant association between vitamin D with GP compared to healthy control. BMD was significantly lower in the lumbar vertebra (L1 -<span style="font-family: "> L4) and femoral neck region (both right and left) among GP children compared to the control group. Conclusion: From this study, it may be concluded that the majority of children with GP had hypovitaminosis D and low BMD status compared to the control. Vitamin D deficiency and low BMD status were significantly associated with children with growing pain. Institutional Review Board (I.R.B.) Clearance Certificate (NO. BSMMU/2020/4503 Date: 15/03/2020) was provided from the office of the Registrar, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
基金a grant from the National Nature Sciences Foundation of China (No. 30672426).
文摘Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.
基金General Program of National Natural Science Foundation of China(No.81873283)Special Project of"Ten Diseases and Ten Drugs"of Beijing Municipal Commission of Science and Technology(No.z171100001717017)。
文摘Objective:To study the effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain.Methods:Walker256 cells were passaged in ascites and injected into the tibia of female Wistar rats to prepare the bone cancer pain model.On the 14th day after model establishment,60 rats were randomly divided into model group,sham-operated group,Yishen Qutong granula low,middle,high dose group and tramadol hydrochloride positive control group.After continuous administration for 14 days,the mechanical pain threshold,thermal threshold and weight-bearing difference of both hind limbs were observed.Results:Compared with the model group,Yishen Qutong groups increased the mechanical pain threshold,thermal pain threshold and reduced the weight difference of both hind limbs(P<0.05).Compared with the positive drug group,there was no significant difference in increasing the mechanical pain threshold and thermal pain threshold of rats in the medium dose group of Yishen Qutong(P>0.05),and Yishen Qutong granula significantly reduced the weight-bearing difference of hind limbs in all groups(P<0.05).Conclusion:Yishen Qutong granula can relieve pain sensitization and alleviate bone damage in rats with bone cancer pain.
文摘As quality and cost effectiveness become essential in clinical practice,an evidencebased evaluation of the utility of imaging orders becomes an important consideration for radiology’s value in patient care.We report an institutional quality improvement project including a retrospective review of utility of sacrum magnetic resonance(MR)imaging for low back pain at our institution over a four-year period and follow-up results after physician education intervention.Sacral MR imaging for low back pain and tailbone pain were only positive for major findings in 2/98(2%)cases,and no major changes in patient management related to imaging findings occurred over this period,resulting in almost$500000 cost without significant patient benefit.We distributed these results to the Family Medicine department and clinics that frequently placed this order.An approximately 83%drop in ordering rate occurred over the ensuing 3 mo follow-up period.Sacrum MR imaging for low back pain and tail bone pain has not been a cost-effective diagnostic tool at our institution.Physician education was a useful tool in reducing overutilization of this study,with a remarkable drop in such studies after sharing these findings with primary care physicians at the institution.In conclusion,sacrum MR imaging rarely elucidates the cause of low back/tail pain diagnosed in a primary care setting and is even less likely to result in major changes in management.The practice can be adopted in other institutions for the benefit of their patients and improve cost efficiency.
