JNK in Spinal Cord Facilitates Bone Cancer Pain in Rats through Modulation of 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.

Effects of p38 MAPK inhibitor on the rat pain behavior and proinflammatory cytokines in a metastatic bone cancer pain model

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.

The effects of Yishen Qutong granula on pain sensitization and bone destruction of rats with bone cancer pain

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.

Modulation of Na_v1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain

Given that lysophosphatidic acid（LPA） and the tetrodotoxin-resistant sodium channel Na_v1.8 are both involved in bone cancer pain, the present study was designed to investigate whether crosstalk between the LPA receptor LPA_1（also known as EDG2） and Na_v1.8 in the dorsal root ganglion（DRG） contributes to the induction of bone cancer pain. We showed that the EDG2 antagonist Ki16198 blocked the mechanical allodynia induced by intrathecal LPA in na？ve rats and attenuated mechanical allodynia in a rat model of bone cancer. EDG2 and Na_v1.8expression in L_（4-6）DRGs was upregulated following intrathecal or hindpaw injection of LPA. EDG2 and Na_v1.8expression in ipsilateral L_（4-6）DRGs increased with the development of bone cancer. Furthermore, we showed that EDG2 co-localized with Na_v1.8 and LPA remarkably enhanced Na_v1.8 currents in DRG neurons, and this was blocked by either a protein kinase C（PKC） inhibitor or a PKCe inhibitor. Overall, we demonstrated the modulation of Na_v1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced.

Inhibition of Glial Activation in Rostral Ventromedial Medulla Attenuates Mechanical Allodynia in a Rat Model of Cancer-induced Bone Pain

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.

Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Background. 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. Methods. 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. Results. 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). Conclusions. 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.

Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain

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.

Effect of down-regulation of voltage-gated sodium channel Nav1.7 on activation of astrocytes and microglia in DRG in rats with cancer pain

Objective:To evaluate the effect of down-regulation of Nav1.7 on the activation of astrocytes and microglia in DRG of rats with cancer pain,and explore the transmission of the nociceptive information.Methods:Lentiviral vector harboring RNAi sequence targeting the Navl.7 gene was constructed,and Walker 256 breast cancer cell and morphine was injected to build the bone cancer pain model and morphine tolerance model in rats.Lentiviral vector was injected.Rats in each model were divided into 4 groups:model group,PBS group,vehicle group and LV-Nav1.7 group.The expression levels of GFAP and OX42 in dorsal root ganglia(DRG) were measured.Results:After the animal model was built,the level of Navl.7,GFAP and OX42 was improved obviously with the time prolonged,which was statistically significant(P<0.05).The expression level of GFAP and OX42 in the DRG in the LV-Navl.7 group declined obviously compared to the model group,PBS group and vehicle group(P<0.05).Conclusions:Intrathecal injection of Navl.7 shRNA lentiviral vector can reduce the expression of Nav1.7and inhibit the activation of astrocytes and microglia in DRG.The effort is also effective in morphine tolerance bone cancer pain model rats.

阶梯式心理干预对骨癌患者疼痛、负性情绪及生活质量的影响

目的 探讨阶梯式心理干预对骨癌患者疼痛、负性情绪及生活质量的影响。方法 将120例骨癌患者按干预方法的不同分为观察组(n=60)和对照组(n=60)。两组患者均接受常规治疗,观察组在对照组的基础上加用阶梯式心理干预。比较两组患者数字分级评分法(NRS)、医院焦虑抑郁量表(HADS)、健康调查简表(SF-36)、匹兹堡睡眠质量指数(PSQI)评分。结果 复查时,观察组患者NRS、PSQI评分均明显低于对照组,差异均有统计学意义(P﹤0.01)。复查时,两组患者HADS-A和HADS-D评分均低于入院时,观察组患者HADS-A和HADS-D评分均低于对照组,差异均有统计学意义(P﹤0.05)。复查时,两组患者生理功能、情感职能、精神健康、社会功能评分均高于本组入院时,观察组患者生理功能、情感职能、精神健康、社会功能评分均高于对照组,差异均有统计学意义(P﹤0.05)。结论 阶梯式心理干预能有效缓解骨癌患者疼痛,改善负性情绪,提高生活质量与睡眠质量。

右美托咪定通过脊髓MrgC受体参与调控小鼠骨癌痛吗啡耐受

目的:通过骨癌痛(bone cancer pain,BCP)小鼠模型明确右美托咪定是否参与吗啡耐受并探索其机制。方法:使用Lewis肺癌细胞系制备C57BL/6小鼠股骨癌痛动物模型。对BCP小鼠进行鞘内置管,连续7天注射吗啡诱导耐受产生。von Frey纤维丝评估小鼠左后足50%机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT)、热板法评估热缩足潜伏期阈值(thermal withdrawal threshold,TWL)。给药第7天后取L3~L5节段脊髓,使用免疫组化实验和Western Blotting(WB)方法检测小鼠脊髓Mas相关基因C受体(Mas-related gene C receptor,MrgC)的表达。通过对吗啡耐受的BCP小鼠鞘内注射右美托咪定,探索其可能的机制。结果:自建模后第7天起,BCP小鼠左后足50%MWT显著下降,TWL明显缩短(P<0.05)。建模后第14天起鞘内给予吗啡,给药的第1~4天,BCP小鼠左后足50%MWT明显上升,TWL明显增加(P<0.05),给药的第5天开始50%MWT逐渐下降,TWL明显缩短。但预先鞘内给予右美托咪定后,给药的第1~7天BCP小鼠左后足50%MWT持续增高,TWL持续延长(P<0.05),且免疫组化和WB结果显示MrgC表达明显增加。结论:右美托咪定可缓解BCP小鼠吗啡耐受的形成,这一作用可能与右美托咪定促进BCP小鼠脊髓MrgC表达和活化有关。

人参皂苷Rg3对乳腺癌骨转移大鼠疼痛的缓解作用及机制研究

目的:研究人参皂苷Rg3缓解乳腺癌骨转移大鼠痛觉行为的作用及机制。方法:采用大鼠乳腺癌细胞注入胫骨骨髓腔内构建乳腺癌骨转移疼痛模型;随机分成假性手术组、模型组以及人参皂苷Rg3给药组;连续3天静脉注射人参皂苷Rg3;记录大鼠痛觉行为学变化;分子对接分析人参皂苷Rg3与蛋白质的结合;免疫荧光和免疫印迹法检测各组动物脊髓组织炎症相关蛋白表达变化。结果:乳腺癌骨转移可导致骨组织损伤,诱发大鼠机械痛敏、热痛敏及自发痛。同时脊髓胶质细胞和NLRP3炎症小体激活,促炎因子IL-1β表达上调,抗氧化因子Nrf2和GPX4表达下降,线粒体氧化损伤相关蛋白DHODH和细胞色素C表达增加。人参皂苷Rg3给药后,大鼠机械痛、热痛和自发痛缓解,脊髓炎症信号下降,抗氧化Nrf2/GPX4信号增加,线粒体过氧化物信号下降。分子对接显示人参皂苷Rg3可结合Nrf2。结论:人参皂苷Rg3激活Nrf2介导的抗氧化反应,降低脊髓炎症,从而缓解癌痛。

淫羊藿素联合吗啡对骨癌痛小鼠的镇痛效应研究

目的:探究淫羊藿素对骨癌痛(bone cancer pain,BCP)小鼠的镇痛效应,以及淫羊藿素与吗啡联合用药的镇痛效应;确定半效剂量淫羊藿素与吗啡联合用药,在达到吗啡最大镇痛效应时所减少的吗啡用量。方法:使用雄性C57BL/6J小鼠及路易斯(Lewis)肺癌细胞建立BCP小鼠模型。通过测定机械刺激缩足反射阈值(mechanical withdrawal threshold,MWT),冷刺激缩足潜伏期(paw withdrawal latency,PWL)以及自发抬足次数和抬足保护时间以评估小鼠疼痛敏感度。结果:自造模后第7~14天起,BCP小鼠左侧(荷瘤侧)后爪MWT和PWL明显降低,自发抬足次数和抬足保护时间明显上升,并持续存在(P<0.05)。造模后第7~14天给予淫羊藿素,自第10~14天起淫羊藿素明显增加BCP小鼠左侧后爪的MWT和PWL,并减少自发抬足次数和抬足保护时间,停药后效应持续至造模后第18天(即停药后第4天)(P<0.05)。应用2倍EC50剂量淫羊藿素(200 mg/kg)与吗啡联合用药可明显延长停药后镇痛效应,停药后镇痛效应持续至造模后第21天(即停药后第7天)(P<0.05)。应用半效剂量淫羊藿素(100 mg/kg)与吗啡联合用药,达到吗啡最佳镇痛效应时最多可减少60%吗啡用量。结论:淫羊藿素对BCP小鼠有明显的镇痛效应,当与吗啡联合用药时,不仅明显延长了停药后的镇痛效应,还能够减少高达60%的吗啡用量。

针刺治疗肿瘤并发症的临床研究进展

针刺作为传统的中医疗法,作用于不同腧穴具有疏经通络、益气活血的功效。中医认为阳虚、气滞、血阻是肿瘤并发症的主要发病机制,近年来针刺广泛用于治疗肿瘤及其并发症,且效果显著。基于此,以“恶性肿瘤、针刺治疗、临床观察、临床研究”为主题对2001—2021年CNKI数据库进行检索,共计检索文献357篇,归纳、整理相关文献37篇,主要从肿瘤癌性疼痛、胃肠道反应、骨髓抑制、癌性疲乏、抑郁、睡眠障碍、周围神经病变等方面进行概述,旨在探析针刺治疗肿瘤并发症的可行性,为肿瘤及其并发症的临床治疗和研究提供依据。

电针调控脊髓背角NRG1及小胶质细胞活化缓解癌性骨痛研究

目的观察电针腰(L)3~L5“夹脊”对癌性骨痛(CIBP)大鼠疼痛行为及脊髓背角神经调节蛋白1(NRG1)表达和小胶质细胞活化的影响,探讨电针缓解CIBP的作用机制。方法30只雌性SD大鼠随机分为假手术组、模型组和电针组,每组10只。向模型组和电针组大鼠右侧胫骨骨髓腔内注射10μL Walker 256乳腺癌细胞,假手术组注射10μL Hank's液。于术后15 d开始,选取双侧L3~L5“夹脊”进行电针治疗30 min,每日1次,共6次。于术前(0 d)和术后3、7、10、14、16、18、20 d进行机械性痛觉敏化测试。Western blot检测L4~L6脊髓背角NRG1的蛋白表达;免疫荧光组织化学法检测脊髓背角离子钙结合适配器分子1(Iba-1)和NRG1的表达;ELISA检测L4~L6脊髓背角肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6的含量。结果与假手术组相比,模型组大鼠自术后7 d开始右后肢机械缩足反射阈值(MWT)显著下降(P<0.001),L4~L6脊髓背角NRG1蛋白表达明显增加(P<0.05),且Iba-1与NRG1的共表达显著增加(P<0.01),TNF-α、IL-1β、IL-6含量明显升高(P<0.001)。与模型组相比,术后15 d开始电针治疗后,电针组大鼠右后肢MWT显著上升(P<0.001),L4~L6脊髓背角NRG1蛋白表达明显降低(P<0.05),且Iba-1与NRG1的共表达显著减少(P<0.01),TNF-α、IL-1β、IL-6含量明显降低(P<0.001)。结论电针双侧“夹脊”可有效缓解CIBP大鼠的疼痛行为,其机制可能与抑制脊髓背角NRG1的上调及小胶质细胞的活化有关。

艾灸联合双膦酸盐治疗中重度骨转移癌痛患者的临床效果

目的探究艾灸联合双膦酸盐治疗中重度骨转移癌痛患者的临床效果。方法选取2021年3月至2023年1月赣州市肿瘤医院收治的90例中重度骨转移癌痛患者作为研究对象,根据随机数字表法将其分为对照组(n=30)、研究A组(n=30)和研究B组(n=30)。对照组口服羟考酮缓释片,研究A组在此基础上给予双膦酸盐治疗,研究B组在研究A组基础上给予艾灸治疗。比较三组患者临床疗效、镇痛起效和持续情况、生活质量情况。结果研究B组临床疗效高于研究A组与对照组,差异有统计学意义(P<0.017)。三组患者镇痛起效时间比较,差异无统计学意义(P>0.05)。研究B组镇痛起效时间短于研究A组与对照组,镇痛持续时间长于研究A组与对照组,差异有统计学意义(P<0.05)。治疗前,三组患者生活质量比较,差异无统计学意义(P>0.05)。治疗4周后,研究B组患者睡眠、日常活动及精神状态各维度评分高于研究A组与对照组,且研究A组睡眠评分高于对照组,差异有统计学意义(P<0.05);三组患者生活质量的食欲维度评分比较,差异无统计学意义(P>0.05)。结论艾灸联合双膦酸盐治疗中重度骨转移癌痛患者,可缩短镇痛起效时间,延长镇痛持续时间,提高患者生活质量和临床疗效。

针刺治疗骨转移癌痛的临床及机制研究进展

骨转移癌痛是中重度癌症疼痛最常见的类型,其发病机制复杂,目前机制研究多集中在兴奋脊髓神经元、激活胶质细胞、不同受体的活化等方面。目前治疗药物存在一定的不良反应。临床研究表明针刺治疗骨转移癌痛可以减轻药物耐受和不良反应、增进疗效,减少镇痛药物的剂量,同时改善病人的焦虑、抑郁症状,提高生存质量。针刺可能通过调节神经递质释放、抑制胶质细胞活化以及调节下行抑制和易化系统等途径发挥镇痛效应。本文就骨转移癌痛的发病机制及针刺治疗骨癌痛的临床及基础研究进行综述,以期进一步为针刺镇痛的机制研究及临床应用提供科学依据。

核心岩藻糖基化修饰调控NLRP3介导骨癌性疼痛的作用机制

目的研究核心岩藻糖基化(core fucosylation,CF)修饰对骨癌性疼痛的作用,并探究其作用机制。方法收集我院骨癌性疼痛患者30例,随机选取一半患者使用传统镇痛类药物吗啡治疗,设为吗啡组;另一半患者设为对照组。采用数字疼痛评分法(numerical rating scales,NRS)对所有患者进行疼痛评分;蛋白免疫印迹及ELISA实验观察患者血清及骨髓上清液中NLRP3、IL-1β、IL-18的表达情况;免疫沉淀观察NLRP3及CF修饰的变化。构建乳腺癌致骨癌性疼痛大鼠模型,将40只健康成年SD大鼠分为对照组、模型组、FUT8shRNA组、吗啡组。免疫荧光检测脊髓组织中CF修饰的变化特征;合成腺病毒包装的FUT8shRNA抑制大鼠体内CF修饰后检测脊髓组织中NLRP3、TNF-α、IL-1β、IL-18的表达变化;利用VonFrey纤维丝测痛仪测量后爪对VonFrey纤维丝刺激的触觉异常性疼痛敏感性,通过缩爪机械阈值(PWT)和自由行走疼痛评分观察骨癌性疼痛对大鼠疼痛行为的影响,比较两种干预方法对NLRP3、TNF-α、IL-1β、IL-18、p38MAPK、PI3K、Akt等蛋白表达变化的影响。结果与对照组相比,吗啡组疼痛强度明显降低、持续时间变短(P<0.05);吗啡组血清及骨髓上清液中NLRP3、IL-1β、IL-18表达明显下调(P<0.05);免疫沉淀实验结果显示,吗啡组NLRP3及CF修饰的水平明显下降(P<0.05)。在体内实验中,与对照组相比,模型组大鼠CF修饰表达明显升高(P<0.05);LCA、TNF-α、IL-1β、IL-18的水平显著上升(P<0.01);大鼠机械性触诱发痛和热痛觉过敏明显加重(P<0.05);NLRP3、TNF-α、IL-1β、IL-18、p38MAPK、PI3K、Akt表达显著上调(P<0.05);与模型组相比,FUT8shRNA组和吗啡组大鼠CF修饰表达明显降低(P<0.05);NLRP3、TNF-α、IL-1β、IL-18的水平显著下降(P<0.01);大鼠机械性触诱发痛和热痛觉过敏明显缓解(P<0.05);NLRP3、TNF-α、IL-1β、IL-18、p38MAPK、PI3K、Akt表达显著下调(P<0.05)。结论抑制CF修饰可对骨癌性疼痛发挥保护作用,其作用机制可能与调控p38MAPK/PI3K/Akt/NLRP3信号通路有关。

羟考酮剂量优化对乳腺癌骨转移癌痛患者镇痛效果及安全性的影响

目的分析羟考酮剂量优化对乳腺癌骨转移癌痛患者镇痛效果及安全性的影响。方法前瞻选择2020年1月-2022年1月医院88例乳腺癌骨转移癌痛患者作为研究对象,随机数字表法分为两组各44例,在排除药物禁忌和明确疼痛严重程度后,给予所有患者乙酰氨基酚片口服治疗14d,治疗期间观察组加用低剂量的羟考酮缓释片;对照组治疗前7d加用常规剂量羟考酮缓释片,7d后改服低剂量羟考酮缓释片。治疗14d,比较两组镇痛效果;治疗前、治疗14d,比较两组生命质量[使用乳腺癌患者生命质量测定量表(FACT-B)评估],治疗期间统计不良反应发生情况并比较。结果治疗14d,两组镇痛效果比较,差异无统计学意义(P>0.05);治疗前,两组一般模块(FACT-G)、乳腺癌特异模块评分比较,差异无统计学意义(P>0.05);治疗14d,两组FACT-G、乳腺癌特异模块评分均升高,且观察组FACT-G、乳腺癌特异模块评分均高于对照组,差异有统计学意义(P<0.05);观察组嗜睡、便秘、恶心呕吐、头晕等不良反应总发生率低于对照组,差异有统计学意义(P<0.05)。结论长期应用低剂量羟考酮缓释片治疗乳腺癌骨转移癌痛,不影响整体镇痛效果,在一定程度上还可减少不良反应发生,患者生命质量提高,有较高的临床应用价值。

PGC-1α介导线粒体生物发生对骨癌痛伴发镜像痛的影响

目的:探讨过氧化物酶体增殖物激活受体-γ共激活因子-1α (peroxisome proliferator-activated receptor-γ coactivator-1α, PGC-1α)调控线粒体生物发生对骨癌痛伴发镜像痛的影响。方法:第一部分实验:成年雌性SD大鼠按照随机数字表法分成2组,假手术组(Sham组)与骨癌痛组(bone cancer pain, BCP组),每组10只。第二部分实验:大鼠按照随机数字表法分成3组,Sham+vehicle组、BCP+vehicle组、BCP+ZLN(ZLN005,PGC-1α激活剂组),每组25只。将MRMT-1大鼠乳腺癌细胞注入左胫骨髓腔建立BCP大鼠模型,Sham组大鼠注射等体积Hank's平衡盐溶液。第二部分实验中,BCP+ZLN组大鼠鞘内注射ZLN005(单次单剂量100μg/30μl),Sham+vehicle组与BCP+vehicle组注射等体积溶剂。Western blot用于分析大鼠脊髓中PGC-1α、Nrf1和Tfam蛋白表达量。q PCR用于分析mt DNA相对拷贝数。免疫荧光双标染色分析PGC-1α的分布与细胞定位。结果:单侧癌细胞接种诱导BCP大鼠双侧后爪出现机械性痛觉过敏。ZLN005鞘内注射可减轻BCP大鼠双侧后爪的机械性痛觉过敏。在BCP大鼠的脊髓中观察到PGC-1α、Nrf1、Tfam和mt DNA相对拷贝数水平下降。鞘内注射ZLN005后,PGC-1α、Nrf1、Tfam和mt DNA相对拷贝数的水平升高。PGC-1α在同侧和对侧脊髓背角均有分布。PGC-1α的荧光强度在BCP大鼠双侧脊髓中出现下降。PGC-1α主要与神经元共定位。结论:脊髓中的线粒体生物发生的损伤促进了骨癌痛伴发镜像痛的发生发展。PGC-1α激活介导线粒体生物发生缓解骨癌痛及其伴发的镜像痛。

全程化疼痛管理在晚期肺癌骨转移疼痛患者中的应用效果

目的探讨全程化疼痛管理在晚期肺癌骨转移疼痛患者中的应用效果。方法选取126例肺癌骨转移疼痛患者,将2020年1月至2021年6月接受常规疼痛管理的68例患者作为对照组,将2021年7月至2022年12月接受全程化疼痛管理的58例患者作为观察组。比较两组患者的数字分级评分法(NRS)评分、爆发性疼痛发生情况、癌痛状况[美国疼痛学会病人结局问卷修订量表(APS-POQ-Medified)]、心理状态[抑郁自评量表(SDS)、焦虑自评量表(SAS)]、生活质量[欧洲癌症研究与治疗组织生命质量测定量表(EORTC QLQ-C30)]及护理满意度。结果干预后,两组患者NRS评分均低于本组干预前,观察组患者NRS评分低于对照组,对照组患者爆发性疼痛发生率为42.65%,高于观察组患者的13.79%,差异均有统计学意义(P﹤0.05)。干预后,两组患者疼痛控制满意度评分均高于本组干预前,疼痛程度、疼痛影响、疼痛信念评分均低于本组干预前,观察组患者疼痛控制满意度评分高于对照组,疼痛程度、疼痛影响、疼痛信念评分均低于对照组,差异均有统计学意义(P﹤0.05)。干预后,两组患者SDS、SAS评分均低于本组干预前,观察组患者SDS、SAS评分均低于对照组,差异均有统计学意义(P﹤0.05)。干预后,两组患者EORTC QLQ-C30量表各维度评分均高于本组干预前,观察组患者EORTC QLQ-C30量表各维度评分均高于对照组,差异均有统计学意义(P﹤0.05)。观察组患者的护理满意度为98.28%,明显高于对照组患者的80.88%,差异有统计学意义(P﹤0.01)。结论全程化疼痛管理应用于晚期肺癌骨转移疼痛患者中,能够明显改善疼痛程度和负性情绪,提高生活质量和护理满意度。