Management of pain in patients with bone metastases.

Cancer-induced bone pain (CIBP) has a considerable impact on patients' quality of life as well as physical and mental health. At present, patients with CIBP are managed according to the three-step analgesic therapy algorithm proposed by the World Health Organization. Opioids are commonly used as the first-line treatment for moderate-to-severe cancer pain but are limited due to addiction, nausea, vomiting and other gastrointestinal side effects. Moreover, opioids have a limited analgesic effect in some patients. In order to optimize the management of CIBP, we must first identify the underlying mechanisms. In some patients, surgery, or surgery combined with radiotherapy or radiofrequency ablation is the first step in the management of CIBP. Various clinical studies have shown that anti-nerve growth factor (NGF) antibodies, bisphosphonates, or RANKL inhibitors can reduce the incidence and improve the management of cancer pain. Herein, we review the mechanisms of cancer pain and potential therapeutic strategies to provide insights for optimizing the management of CIBP.

Acupuncture as a Complementary Therapy for Cancer-Induced Bone Pain: A Systematic Review and Meta-Analysis.

Background: Cancer-induced bone pain (CIBP) is a special type of cancer pain and lacks safe and effective treatments. Acupuncture is a potentially valuable treatment for CIBP, studies evaluating the effect of acupuncture on CIBP have increased significantly, but the safety and efficacy of acupuncture to control CIBP remains controversial. Objective: To provide the first meta-analysis to evaluate the safety and efficacy of acupuncture in CIBP management. Data Sources: CNKI, CBM, Wanfang, VIP Database, PubMed, Embase, and Cochrane Library were searched from their inception until 1 June 2022. Study Selection: RCTs with primary bone tumor patients or other types of primary cancer companied by bone metastases as the research subjects and to evaluate the efficacy of acupuncture treatment alone or combined with the control treatment were included. Meanwhile, RCTs should choose the pain score as the primary outcome and pain relief rate, frequency of breakthrough pain, analgesic onset time, analgesia duration, quality of life, and adverse events as reference outcomes. Data Collection and Analysis: We designed a data-extraction form that was used to extract key information from the articles. Data extraction study evaluation was conducted independently by two reviewers, and a third reviewer would resolve any disagreements. The risk of bias was assessed by the Cochrane Collaboration's tool for assessing the risk bias. The quality of the evidence for main outcomes was evaluated by the GRADE system. Mean differences (MD), relative risk (RR), and 95% confidence intervals (CIs) were calculated. The forest plots were performed using the Review Manager Software (5.3 version). Subgroup analysis was used to investigate the possible sources of potential heterogeneity. Descriptive analysis was performed in case of unacceptable clinical heterogeneity. Results: Thirteen RCTs (with 1,069 patients) were included, and all studies were at high risk of bias owing to lack of blinding or other bias. Eleven studies evaluated the effectiveness of acupuncture as a complementary therapy, and showed that acupuncture plus control treatment (compared with control treatment) was connected with reduced pain intensity (MD = -1.34, 95% CI -1.74 to -0.94; Q < 0.1; I 2 = 98%, P < 0.01). Subgroup analyses based on acupoints type partly explain the potential heterogeneity. The results also showed that acupuncture plus control treatment (compared with control treatment) was connected with relieving pain intensity, increasing the pain relief rate, reducing the frequency of breakthrough pain, shortening analgesic onset time, extending the analgesic duration, and improving the quality of life. We have no sufficient evidence to prove the effectiveness of acupuncture alone. Four RCTs reported only adverse events related to opioids' side effects. Evidence was qualified as "very low" because of low methodological quality, considerable heterogeneity, or a low number of included studies. Conclusion: Acupuncture has a certain effect as a complementary therapy on pain management of CIBP, which not only mitigates the pain intensity but also improves the quality of life and reduces the incidence of opioids' side effects, although the evidence level was very low. In future, a larger sample size and rigorously designed RCTs are needed to provide sufficient evidence to identify the efficacy and safety of acupuncture as a treatment for CIBP.

Health-Related Quality of Life Among Patients With Sickle Cell Disease in an Adult Hematology Clinic in a Tertiary Hospital in Lagos, Nigeria.

Background Sickle cell disease (SCD) is a genetic disease of public health concern. Improved quality healthcare has increased the life expectancy of these patients; however, they also face an increased frequency of vaso-occlusive crises and other SCD complications. These complications affect their quality of life, an area of care, which healthcare providers often overlook. We sought to determine the health-related quality of life among patients living with sickle cell disease in Lagos, Nigeria.  Materials and methods We conducted a cross-sectional study of 198 patients with sickle cell disease who attended the adult sickle cell clinic at a tertiary hospital in Lagos, Nigeria, during the period from October 1, 2018, to February 28, 2019. A self-administered questionnaire was used to obtain the clinical and socio-demographic characteristics of the patients and the 35-item Short-Form Health Survey (SF-36) questionnaire was used to determine their health-related quality of life (HRQoL). Determinants of HRQoL were established using bivariate and multivariate regression analysis.  Results The mean age of the 198 patients who participated in the study was 28.4±9.1 years, mean steady-state hemoglobin was 8.2 ± 1.3 g/dl, and 85 (42.9%) patients had a monthly income of 150 USD or less. In the previous year, 65 (32.1 %) and 33 (16.6%) patients, respectively, suffered one to two episodes (s) of acute bone pain crises and acute chest syndrome, and 43 (24.7%) had blood transfusion. Using the scoring system for SF-36 provided by RAND Health, role limitation due to physical health had the lowest median score of 50 (interquartile range {IQR}: 0-100). On bivariate analysis, bone pain crisis was associated with statistically significant low scores across all the 8 HRQoL domains of the SF36 questionnaire. Other variables, including having received blood transfusion, recent hospitalization, acute chest syndrome, lower level of income, and younger age, were also associated with significantly low scores. On regression analysis, bone pain crisis, level of income, and acute chest syndrome were found to be independent determinants of quality of life in the patients. Conclusion Sickle cell disease has a negative impact on the health-related quality of life of those affected. The presence of bone pain crisis is an important predictor of health-related quality of life in sickle cell disease patients. To improve patient outcomes, healthcare providers should take a holistic approach in evaluating and managing this disease, taking into cognizance how the complications and the financial burden of this disease impact the quality of life of affected patients.

Luteolin relieves lung cancer-induced bone pain by inhibiting NLRP3 inflammasomes and glial activation in the spinal dorsal horn in mice.

BACKGROUND: Bone cancer pain (BCP) is one of the most severe complications in cancer patients. However, the pharmacological therapeutic approaches are limited. Luteolin, a major component of flavones, is widely distributed in plants and plays a critical role in the antinociceptive effects, but whether luteolin could alleviate cancer pain and its underlying mechanisms are not known. HYPOTHESIS/PURPOSE: This study investigated the molecular mechanisms by which luteolin reduced BCP. METHODS: Behavioral, pharmacological, immunohistochemical, and biochemical approaches were used to investigate the effect of luteolin on BCP. RESULTS: Luteolin treatment ameliorated Lewis lung cancer (LLC)-induced bone pain in mice in a dose-dependent manner. Luteolin treatment could inhibit the activation of neurons, glial cells, and NOD-like receptor protein 3 (NLRP3) inflammasomes in the dorsal spinal cord in the BCP mouse model. Furthermore, phosphorylated p-38 mitogen-activated protein kinase (MAPK) in the spinal dorsal horn (SDH) was suppressed by luteolin treatment that could influence the analgesic and glial inhibition effects of luteolin. CONCLUSION: Our results demonstrated that luteolin inhibited neuroinflammation by obstructing glial cell and NLRP3 inflammasome activation via modulating p38 MAPK activity in SDH, ultimately improving LLC-induced BCP.

Electroacupuncture Attenuates Cancer-Induced Bone Pain via NF-κB/CXCL12 Signaling in Midbrain Periaqueductal Gray.

Electroacupuncture (EA) is effective in various chronic pains. NF-κB and CXCL12 modulate the formation of chronic pain. Herein, we hypothesized that EA alleviates cancer-induced bone pain (CIBP) through NF-κB/CXCL12 axis in midbrain periaqueductal gray (PAG), which participates in "top-down" pain modulatory circuits. In order to filter the optimum EA frequency for CIBP treatment, 2, 100, or 2/100 Hz EA was set up. In addition, ipsilateral, contralateral, and bilateral EA groups were established to affirm the optimal EA scheme. Bilateral 2/100 Hz EA was considered as the optimal therapeutic scheme and was applied in a subsequent experiment. Western blotting along with immunofluorescence illustrated that CIBP induces a rapid and substantial increase in CXCL12 protein level and NF-κB phosphorylation in vlPAG from day 6 to day 12. Anti-CXCL12 neutralizing antibody and pAAV-U6-shRNA(CXCL12)-CMV-EGFP-WPRE in vlPAG remarkably improved the mechanical pain threshold of the hind paw in CIBP model relative to the control. EA inhibited the upregulation of pNF-κB and CXCL12 in vlPAG of CIBP. The recombinant CXCL12 and pAAV-CMV-CXCL12-EF1a-EGFP-3Xflag-WPRE reversed the abirritation of EA in the CIBP rat model. NF-κB phosphorylation mediated-CXCL12 expression contributed to CIBP allodynia, whereas EA suppressed NF-κB phosphorylation in CIBP. According to the above evidence, we conclude that bilateral 2/100 Hz EA is an optimal therapeutic scheme for CIBP. The abirritation mechanism of EA might reduce the expression of CXCL12 by inhibiting the activation of NF-κB, which might lead to the restraint of descending facilitation of CIBP.

Non-endemic skeletal fluorosis: Causes and associated secondary hyperparathyroidism (case report and literature review).

Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and vitamin D (D) deficiency can exacerbate SF. A 51-year-old man with years of musculoskeletal pain and opiate use was hypocalcemic with secondary hyperparathyroidism upon manifesting recurrent long bone fractures. He smoked cigarettes, drank large amounts of cola beverage, and consumed little dietary Ca. Then, after 5 months of Ca and D3 supplementation, serum 25(OH)D was 21 ng/mL (Nl, 30-100), corrected serum Ca had normalized from 7.8 to 9.4 mg/dL (Nl, 8.5-10.1), alkaline phosphatase (ALP) had decreased from 1080 to 539 U/L (Nl, 46-116), yet parathyroid hormone (PTH) had increased from 133 to 327 pg/mL (Nl, 8.7-77.1). Radiographs revealed generalized osteosclerosis and a cystic lesion in a proximal femur. DXA BMD Z-scores were +7.4 and +0.4 at the lumbar spine and "1/3" radius, respectively. Bone scintigraphy showed increased uptake in two ribs, periarticular areas, and proximal left femur at the site of a subsequent atraumatic fracture. Elevated serum collagen type I C-telopeptide 2513 pg/mL (Nl, 87-345) and osteocalcin >300 ng/mL (Nl, 9-38) indicated rapid bone turnover. Negative studies included hepatitis C Ab, prostate-specific antigen, serum and urine electrophoresis, and Ion Torrent mutation analysis for dense or high-turnover skeletal diseases. After discovering markedly elevated F concentrations in his plasma [4.84 mg/L (Nl, 0.02-0.08)] and spot urine [42.6 mg/L (Nl, 0.2-3.2)], a two-year history emerged of "huffing" computer cleaner containing difluoroethane. Non-decalcified histology of a subsequent right femur fracture showed increased osteoblasts and osteoclasts and excessive osteoid. A 24-hour urine collection contained 27 mg/L F (Nl, 0.2-3.2) and <2 mg/dL Ca. Then, 19 months after "huffing" cessation and improved Ca and D3 intake, yet with persisting bone pain, serum PTH was normal (52 pg/mL) and serum ALP and urine F had decreased to 248 U/L and 3.3 mg/L, respectively. Our experience combined with 15 publications in PubMed concerning unusual causes of non-endemic SF where the F source became known (19 cases in all) revealed: 11 instances from high consumption of black tea and/or F-containing toothpaste, 1 due to geophagia of F-rich soil, and 7 due to "recreational" inhalation of F-containing vapors. Circulating PTH measured in 14 was substantially elevated in 2 (including ours) and mildly increased in 2. The severity of SF in the cases reviewed seemed to reflect cumulative F exposure, renal function, and Ca and D status. Several factors appeared to influence our patient's skeletal disease: i) direct anabolic effects of toxic amounts of F on his skeleton, ii) secondary hyperparathyroidism from degradation-resistant fluorapatite bone crystals and low dietary Ca, and iii) impaired mineralization of excessive osteoid due to hypocalcemia.

Management of cancer pain with analgetic adjuvant and weak opioid in prostate cancer bone metastases: A case series.

BACKGROUND: In cancer patients, cancer pain is the most common cancer complication. About 60-90% of patients with advanced stage cancer experience various levels of pain, and about 30% of patients have been suffering from persistent severe pain. Bones are the most frequent targets of metastases in patients with cancer such as breast, prostate, lung, kidney, and thyroid. In advanced prostate cancer, bone metastasis leads to bone pain, skeletal fracture, and increased mortality. At least 75% of patients with bone metastasis experience bone pain. CASE DESCRIPTION: We report three cases of cancer pain, treated with primary cancer from the prostate metastasis to the spine. All three patients had lower back pain that radiated to the left and right limbs, with mixed pain and bone pain, where early hospital admission shows the Numeric Rating Scale (NRS) pain scale 9-10. Treated with administration of adjuvant therapy (Gabapentin) and weak opioids (injections of Tramadol) as well as injections of Metylprednisolone (for 3 days), the patient's pain scale was evaluated, and the average NRS obtained on days 2-4 was 5-6. On day 5-8, treatment continued with Gabapentin and Tramadol injections, and the pain scale (NRS) decreased to 2-3. All patients on the 8-9th day of treatment also received Biphosphonates to reduce pain, bone damage, fracture risk, and blood calcium levels. Patients can be discharged with an oral Gabapentin prescription only. CONCLUSION: A pain scale (NRS) reduction of >50% is obtained from the initial pain scale in cancer pain patients treated using a combination of adjuvant therapy and weak opioids.

Chanling Gao Attenuates Bone Cancer Pain in Rats by the IKKß/NF-κB Signaling Pathway.

Cancer pain is one of the most common and serious symptoms of cancer patients. At present, the agents used for the prevention or treatment of cancer pain do not act with optimal safety and efficacy. The nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) play an important regulatory role in the developmental process of cancer pain. IKKß is a key molecule of the IκB (IKK) kinase that propagates cellular responses to inflammation. Previous studies have shown that phosphorylation and degradation of the IκBα protein promotes the activation of NF-κB and the expression of TNF-α, IL-1ß, and IL-6, participating in the formation and development of cancer pain. Chanling Gao (CLG) is a compound preparation of traditional Chinese medicine. It contains specific functions, namely nourishing Yin, activating blood circulation and relieving pain and dysfunction syndrome. It is used in the treatment of a variety of pain disorders including cancer-induced bone pain (CIBP), which has a certain relief effect. However, its mechanism of action still remains unclear. In the present study, a rat model of tibia CIBP was successfully established using the Walker 256 breast cancer cell line. The IKKß/NF-κB signaling pathway and its related factors TNF-α, IL-1ß, and IL-6 were used as the entry points to explore the effect of CLG on CIBP and their possible mechanisms of action. The results indicated that CLG improved the body mass of the CIBP rat model and increased the pain threshold in rats. CLG significantly inhibited the degradation of IκBα and the levels of p-IκBα, p-IKKß, and p-p65 NF-κB proteins in the spinal cord of CIBP rats, inhibiting the contents of TNF-α, IL-1ß, and IL-6. Therefore, we conclude that the analgesic effect of CLG in this rat model of CIBP may be related to the inhibition of the IKKß/NF-κB signaling pathway and the reduction of synthesis and release of TNF-α, IL-1ß, and IL-6.

Managing Pain in the Older Cancer Patient.

PURPOSE OF REVIEW: This paper aims to give the specialist and non-specialist alike an overview of the considerations involved in the management of cancer-related pain in the older population. RECENT FINDINGS: Comprehensive guidelines on cancer pain management have been published recently by expert bodies. Cancer pain differs in many respects to other pain conditions and we are likely to encounter it more frequently in older patients in the future. The elderly are more sensitive to the effects of many analgesic medications. The elderly patient with cancer pain presents a unique challenge to the treating physician. The biological effects of ageing impact on the efficacy of many pain management strategies as well as its diagnosis and assessment. Treatment options can be broadly divided into pharmacological, non-pharmacological and interventional. A multidisciplinary approach and frequent re-assessment are essential in achieving favourable outcomes in this patient group.

Evaluating the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases: A phase 2 clinical trial.

INTRODUCTION: Since the survival time of patients with bony metastases has noticeably improved in recent years, these patients are at high risk of complications associated with this metastasis. Hence, the appropriate choice of treatment modality or combination of therapeutic approaches can lead to increasing bone pain relief, improving quality of life, etc. This study is aimed to evaluate the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases. PATIENTS AND METHODS: In a single-arm clinical trial, 23 eligible patients (14 female and 9 male) with the mean age of 67 years old and suffering from bony metastases were enrolled in the study. Two hours after radiotherapy, the patients underwent hyperthermia for 1 h in the supine position. All the patients completed the brief pain inventory (BPI) assessment tool and quality of life questionnaire (QLQ-C30) from the European Organization for Research and Treatment of Cancer (EORTC) at the baseline, end of the treatment and 1, 2 and 3 months thereafter. The response to the treatment was assessed as the zero score (complete response) or two or more than two-point drop of the worst pain within the preceding 24 h (partial response) during the 3-month posttreatment. RESULTS: All the pain intensity and interference scores, except the pain interference with the enjoyment of life score, significantly decreased. A total of 18 out of 23 patients (78%) achieved complete or partial response. The number of patients using pain relief medications decreased from 74% (n=17) at the baseline to 48% (n=11) 3 months later. Moreover, except for nausea and vomiting, appetite loss, diarrhea and financial impact problems, the patients' quality of life improved significantly in all the functional scales and symptoms within 3 months. CONCLUSION: This study showed that using hyperthermia in combination with radiotherapy significantly ameliorated bone pain among the patients suffering from cancer with painful bony metastases.

Antinociceptive effects of Ginsenoside Rb1 in a rat model of cancer-induced bone pain.

Ginsenoside Rb1 (GRb1) is a major ingredient of ginseng, a traditional medicine that has been used for thousands of years. Previous studies have reported that GRb1 had anti-inflammatory, antioxidant and neuroprotective effects. The current study aimed to evaluate the antinociceptive effects of GRb1 in a rat model of cancer-induced bone pain (CIBP) established by intratibial injection of Walker 256 cells. Intraperitoneal injection (i.p.) of GRb1 (5 and 10 mg/kg, but not 1 mg/kg) partially and transiently reversed the mechanical allodynia and thermal hyperalgesia in CIBP rats at 14 days following surgery when the pain behavior is established. Furthermore, repeated administration of GRb1 demonstrated persistent analgesic effect. Additionally, the protein expression and immunoreactivity of iba1, which is the maker of microglia, was significantly suppressed in CIBP rats treated with GRb1 (i.p., 10 mg/kg) from day 12 for three consecutive days compared with CIBP rats treated with a vehicle. Furthermore, upregulation of spinal interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were also significantly inhibited by the treatment of GRb1 (i.p., 10 mg/kg) from day 12 for three consecutive days. Together, these results indicated that GRb1 may attenuate CIBP via inhibiting the activation of microglia and glial-derived proinflammatory cytokines.

Sinomenine attenuates cancer-induced bone pain via suppressing microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades in rat models.

Cancer-induced bone pain is one of the most severe types of pathological pain, which often occurs in patients with advanced prostate, breast, and lung cancer. It is of great significance to improve the therapies of cancer-induced bone pain due to the opioids' side effects including addiction, sedation, pruritus, and vomiting. Sinomenine, a traditional Chinese medicine, showed obvious analgesic effects on a rat model of chronic inflammatory pain, but has never been proven to treat cancer-induced bone pain. In the present study, we investigated the analgesic effect of sinomenine after tumor cell implantation and specific cellular mechanisms in cancer-induced bone pain. Our results indicated that single administration of sinomenine significantly and dose-dependently alleviated mechanical allodynia in rats with cancer-induced bone pain and the effect lasted for 4 h. After tumor cell implantation, the protein levels of phosphorylated-Janus family tyrosine kinase 2 (p-JAK2), phosphorylated-signal transducers and activators of transcription 3 (p-STAT3), phosphorylated-Ca2+/calmodulin-dependent protein kinase II (p-CAMKII), and phosphorylated-cyclic adenosine monophosphate response element-binding protein (p-CREB) were persistently up-regulated in the spinal cord horn. Chronic intraperitoneal treatment with sinomenine markedly suppressed the activation of microglia and effectively inhibited the expression of JAK2/STAT3 and CAMKII/CREB signaling pathways. We are the first to reveal that up-regulation of microglial JAK2/STAT3 pathway are involved in the development and maintenance of cancer-induced bone pain. Moreover, our investigation provides the first evidence that sinomenine alleviates cancer-induced bone pain by inhibiting microglial JAK2/STAT3 and neuronal CAMKII/CREB cascades.

The roles of epigallocatechin-3-gallate in the treatment of neuropathic pain: an update on preclinical in vivo studies and future perspectives.

Neuropathic pain (NP) is a complex and chronic disease caused by lesions or defects of the somatosensory nervous system. The treatments normally used for managing NP usually lack efficacy. Several animal models of NP have been engineered in order to understand the molecular mechanisms underlying NP and to find alternative molecules to use as new therapeutic agents. Preclinical in vivo studies identified the epigallocatechin-3-gallate (EGCG), a main active component of green tea (Camellia sinensis), as a possible therapeutic molecule for NP treatment due to its anti-inflammatory and antioxidant properties. Interestingly, it has been shown that EGCG reduced bone cancer pain. The purpose of this article is to discuss the potential use of EGCG for control and treatment of NP, by reviewing the preclinical studies reported in the literature and by shedding light on the potential schemes based on EGCG's application in clinical practices.

Clinical observation on Qiangjin Zhuanggu Qufeng Mixture in elderly primary osteoporosis / 中草药

Objective: To observe the clinical effect of Qiangjin Zhuanggu Qufeng Mixture on treating elderly primary osteoporosis, which had the effect of formula of nourishing the liver and kidney. Method A total of 100 elderly primary osteoporosis treated in Hangzhou Hospital of Traditional Chinese Medicine were selected and randomly divided into control group and treatment group, 50 cases in each group. The control group was treated with calcium preparations, vitamin D, calcium carbonate, Vitamin D3 Chewable Tablets and Calcitriol Soft Capsules; The treatment group was treated with Qiangjin Zhuanggu Qufeng Mixture on the basis of the control group. All patients were treated for six months. The change of the Chinese medicine symptoms scores was observed, and metastatic bone pain scores and calcaneus bone density was compared. Result The effective rate of traditional Chinese medicine symptoms in the treatment group was significantly better than that in the control group. The metastatic bone pain scores of both groups mitigated after treating, and the treatment group was better. The level of calcaneus bone density improved significantly, but that in two groups had no statistically difference after treating. Conclusion:s Calcium preparations, vitamin D, calcium carbonate, Vitamin D3 Chewable Tablets, and Calcitriol Soft Capsules combined with Qiangjin Zhuanggu Qufeng Mixture could improve traditional Chinese medicine symptoms and bone density, and mitigate metastatic bone pain.

P2X4 receptor in the dorsal horn partially contributes to brain-derived neurotrophic factor oversecretion and toll-like receptor-4 receptor activation associated with bone cancer pain.

Previous studies have suggested that the microglial P2X7 purinoceptor is involved in the release of tumor necrosis factor-α (TNFα) following activation of toll-like receptor-4 (TLR4), which is associated with nociceptive behavior. In addition, this progress is evoked by the activation of the P2X4 purinoceptor (P2X4R). Although P2X4R is also localized within spinal microglia in the dorsal horn, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. With the present rat model of CIBP, we demonstrate a critical role of the microglial P2X4R in the enhanced nociceptive transmission, which is associated with TLR4 activation and secretion of brain-derived neurotrophic factor (BDNF) and TNFα in the dorsal horn. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, P2X4R small interfering RNA (siRNA) was administered intrathecally, and real-time PCR, Western blots, immunofluorescence histochemistry, and ELISA were used to detect the expression of P2X4R, TLR4, OX-42, phosphorylated-p38 MAPK (p-p38), BDNF, and TNFα. Compared with controls, intrathecal injection of P2X4R siRNA could prevent nociceptive behavior induced by ATP plus lipopolysaccharide and CIBP and reduce the expression of P2X4R, TLR4, p-p38, BDNF, and TNFα. In addition, the increase of BDNF protein in rat microglial cells depended on P2X4 receptor signaling, which is partially associated with TLR4 activation. The ability of microglial P2X4R to activate TLR4 in spinal cord leading to behavioral hypersensitivity and oversecretion of BDNF could provide an opportunity for the prevention and treatment of CIBP.

Effect of electroacupuncture treatment on pain behavior and calcitonin-gene related peptide expression in cancer induced bone pain-morphine tolerance rat model / 中华行为医学与脑科学杂志

Objective To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP)-morphine tolerance rat model and the expression of calcitonin-gene related peptide(CGRP) immunohistochemisty in dorsal root ganglion (DRG).Methods Forty SD rats were divided into four groups:sham group,CIBP + morphine tolerance group (BM),CIBP + electroacupuncture group (BE),and CIBP + morphine tolerance + electroacupuncture group (BME).BM,BE and BME groups were prepared CIBP model by carcinoma cell tibia implanted.After six days,the three CIBP groups accepted treatment of morphine,electroacupuncture,and morphine combined electroacupuncture,separately,nine days continuously.Acupoints were selected Zusanli (ST36) and Sanyinjiao (SP6).50％ mechanical withdraw threshold was evaluated by mechanical stimulation.CGRP expression in dorsal root ganglion was detected by immunohistochemisty.Results After five days of electroacupuncture treatment,pain threshold was (10.9 ± 0.8) g in BME group,(8.7 ± 0.6) g in BM group and (6.2 ± 0.9) g in BE group.The results had significant statistic differences (P ＜ 0.01,separately).IOD value of CGRP expression in dorsal root ganglion was 9026.5 ± 1827.4 in BME group,compared with 14803.1 ± 2086.7 in BM group and 15730.6 ± 2712.5 in BE group (P ＜ 0.01,separately).Results Electroacupuncture can relieve CIBP-morphine tolerance rat pain behavior.The mechanism is related to inhibiting CGRP overdue expression in DRG.

The application of external applies and washing of Chinese medicine in the treatment of muscular and bone pain / 国际中医中药杂志

External applies and washing of traditional Chinese medicine has sound curative effect in treating muscular and bone pain.The author reported some his experiences on the treatment of muscular and bone pain with hot applies and tendon-relaxing and collaterals-activating lotion.

A Case of Osteomalacic Myopathy

Osteomalacia is a disorder in which the mineralization of the organic matrix of the skeleton is defective. Proximal muscular weakness is a common symptom of osteomalacia. A 27-year-old woman reported the gradual onset of gait disturbance and bone pain in the thigh. Her height shortened during 10 months. On neurological examinations, proximal muscular weakness of the extremities was disclosed. Serum phosphorus was 1.8 mg/dl (normal 2.5~4.5), alkaline phosphatase was 1045 IU/L (normal 70~290), and 1,25 (OH)2 vitamin D3 was 18 pg/ml (normal 20~60). On roentgenography, multiple pseudofracture lines of the rib and erosion of the head of the right femur were demonstrated. A bone scan showed multiple hot spots on the ribs and right femur. She was medicated with calcitriol and phosphorus and she recovered most of her strength and experienced decreased bone pain after 3 months. We report a case that confirms osteomalacic myopathy by an endocrinological test in patients who experienced gradual proximal muscular weakness and bone pain.