Receptive properties of primary afferent fibres from rabbit pleura,in vitro

Abstract We investigated the physiological properties of mediastinal pleural primary afferent units by recording single nerve fibre activity from the phrenic nerve in an in vitro preparation of rabbit tissue. A total of 41 units with conduction velocities in the group III and IV range were examined for their responsiveness to mechanical, thermal and chemical stimuli. Most receptive fields were adjacent to the phrenic nerve-pericardiacophrenic artery complex. The thresholds to punctate mechanical stimulation (von Frey hairs) were widely scattered around a median of 5.4 mN; all fibres showed slowly adapting responses to mechanical stimulation. Heat sensitivity was observed in 7/41 units (17%), while 17/41 (41%) of the fibres exhibited a spurious transient excitation to strong and rapid cooling. Chemosensitivity was scarce with respect to capsaicin (7/33 (21%) of the units responding) but more common to CO2-saturated synthetic interstitial fluid (pH 6.1, 5/16 (31%) responding). The most effective stimulus was a mixture of bradykinin, serotonin, histamine and prostaglandin E2 ('inflammmatory soup') which evoked stimulus responses in 27/33 (82%) of the afferent fibres challenged. Sensitization to mechanical stimuli occurred in 5/41 (12%) of the units, following the application of heat or inflammatory mediators. The rabbit pleura appears as a tissue mainly innervated by multimodal mechano- and chemosensitive afferent units.     

Perceived discrimination and physical activity mediate the associations between receiving a survivorship care plan and cancer pain

BackgroundSurvivorship care plan helps improve the continuity of care and manage ongoing pain that affects up to 46% of cancer survivors by promoting health behaviors, including physical activity. However, perceived discrimination may decrease the likelihood of cancer survivors participating in physical activities and negatively influence their pain status. Thus, this study aimed to examine the mediating role of physical activity and perceived discrimination in the relationship between receiving a survivorship care plan and cancer pain.MethodsThis cross-sectional, correlational study utilized data from the 2012–2019 Behavioral Risk Factor Surveillance System. Analyses accounted for the complex survey design. Logistic regression was utilized to analyze the association among survivorship care plans, discrimination, physical activity, and pain. Generalized structural equation modeling was conducted to test a hypothesized model in which survivorship care plans and discrimination affect physical activity, and subsequently influence pain status.ResultsForty-two and 81% of survivors reported receiving treatment summaries and follow-up care plans, respectively, and 8% experienced cancer pain. After controlling for covariates, the highest discrimination quintile was three times more likely to report cancer pain than the lowest quintile. While receiving follow-up care plans was positively related to cancer pain, respondents in the third- to fifth- quintiles were less likely to report cancer pain when receiving follow-up care plans than the first quintile respondents. Physical activity mediated the association between discrimination and cancer pain.ConclusionsReverse relationships between receiving follow-up care plans and cancer pain existed; however, discrimination and physical activity mediated these relationships.     

大鼠脊髓小胶质细胞P2X4的表达和糖尿病病理性神经痛大鼠炎症反应和疼痛阈值的关系

摘要 目的：探究大鼠脊髓小胶质细胞P2X4的表达和糖尿病病理性神经痛大鼠炎症反应和疼痛阈值的关系。方法：通过高脂饮食结合链脲佐菌素注射诱导糖尿病病理性神经痛大鼠模型并分为3组：对照组（正常大鼠,腹腔注射载体柠檬酸盐缓冲液0.25 mL/kg）,模型组（糖尿病病理性疼痛模型,同上注射,n=15）和抑制剂组（大鼠糖尿病病理性模型,过鞘内导管注射米诺环素）,共28 d。通过MWT评估对机械刺激的手掌反应。通过双极针电极检测实验大鼠的运动神经传导速速。通过蛋白印迹分析P2X4和BDNF蛋白表达。通过RT-PCR分析炎症因子IL-1β、TNF-α和NLRP3的mRNA表达。通过蛋白印迹分析p38MAPK和p-p38MAPK的蛋白表达。结果：第2week、4week和6week,模型组MWT较对照组降低（P<0.05）,抑制剂组MWT较模型组升高（P<0.05）。第2 week,个实验组大鼠MNCV比较无差异（P>0.05）,第4week和第6week,模型组MNCV较对照组降低（P<0.05）,抑制剂组MNCV较模型组升高（P<0.05）。模型组P2X4和BDNF蛋白表达较对照组升高（P<0.05）,抑制剂组P2X4和BDNF蛋白表达较模型组降低（P<0.05）,模型组P2X4和BDNF mRNA表达较对照组升高（P<0.05）,抑制剂组P2X4和BDNF mRNA表达较模型组降低（P<0.05）。模型组IL-1β、TNF-α和NLRP3的mRNA表达较对照组升高（P<0.05）,抑制剂组IL-1β、TNF-α和NLRP3的mRNA表达较抑制剂组降低（P<0.05）。模型组p-p38MAPK蛋白表达较对照组升高（P<0.05）,抑制剂组p-p38MAPK蛋白表达较模型组降低（P<0.05）,各实验组大鼠p38MAPK蛋白表达无差异（P>0.05）。结论：大鼠脊髓小胶质细胞P2X4-BDNF信号在DNP中起重要作用,并且P2X4在DNP期间激活的脊髓小胶质细胞中表达升高,抑制小胶质细胞激活能显著降低P2X4表达和炎症水平,可防止热痛觉过敏并增加大鼠疼痛阈值。     

夹脊电针疗法联合重复经颅磁刺激对不完全性脊髓损伤后神经病理性疼痛患者心理状态、血清炎性因子和疼痛介质的影响

摘要 目的：观察夹脊电针疗法联合重复经颅磁刺激（rTMS）对不完全性脊髓损伤（ISCI）后神经病理性疼痛（NP）患者心理状态、血清炎性因子和疼痛介质的影响。方法：选择ISCI后并发NP患者113例,根据随机数字表法分为对照组（n=56,rTMS治疗）和研究组（n=57,对照组基础上结合夹脊电针疗法）,连续治疗4周后观察两组疼痛改善、心理状态、血清炎性因子和疼痛介质水平的变化。结果：研究组的临床总有效率高于对照组（P<0.05）。研究组治疗4周后的疼痛评级指数（PRI）、现实疼痛指数（PPI）、视觉模拟评分（VAS）评分低于对照组（P<0.05）。研究组治疗4周后的焦虑自评量表（SAS）、抑郁自评量表（SDS）评分低于对照组（P<0.05）。研究组治疗4周后的肿瘤坏死因子-α（TNF-α）、降钙素原（PCT）低于对照组,白细胞介素-10（IL-10）则高于对照组（P<0.05）。研究组治疗4周后的前列腺素E₂（PGE₂）、5-羟色胺（5-HT）低于对照组,β-内啡肽（β-EP）则高于对照组（P<0.05）。结论：夹脊电针疗法联合rTMS治疗ISCI后NP患者,可有效减轻疼痛症状,改善其心理状态、血清炎性因子和疼痛介质水平。     

掌侧入路、背侧入路微创加压螺钉固定术治疗腕舟骨骨折的疗效比较及对血清创伤应激指标和疼痛介质的影响

摘要 目的：比较掌侧入路、背侧入路微创加压螺钉固定术治疗腕舟骨骨折的疗效,以及分别对血清创伤应激指标和疼痛介质的影响。方法：本研究为回顾性研究,临床资料来源于2018年1月~2021年1月来我院接受治疗的88例腕舟骨骨折患者,根据入路方式的不同分为A组（背侧入路,43例）和B组（掌侧入路,45例）。观察两组患者腕功能优良率、围术期相关指标、视觉疼痛模拟评分（VAS）、腕关节活动度、血清创伤应激指标、疼痛介质情况。结果：两组优良率组间对比未见明显差异（P>0.05）。B组术中出血量少于A组,骨性愈合时间短于A组（P<0.05）,两组手术时间对比无差异（P>0.05）。B组术后6个月VAS评分低于A组（P<0.05）。两组术后1年腕关节掌屈、背伸、桡偏、尺偏活动度均增大（P<0.05）。两组术后3 d皮质醇（Cor）、C反应蛋白（CRP）、促肾上腺皮质激素（ACTH）均升高,但B组低于A组（P<0.05）。两组术后3 d、前列腺素E₂（PGE₂）、P 物质（SP）、β-内啡肽（β-EP）均下降,且B组低于A组（P<0.05）。结论：掌侧入路、背侧入路微创加压螺钉固定术治疗腕舟骨骨折,疗效相当,其中掌侧入路可减少术中出血量,促进骨折愈合,同时还可减轻术后疼痛、术后创伤,综合疗效相对更好。     

Pyrrolinone derivatives as a new class of P2X3 receptor antagonists Part 2: Discovery of orally bioavailable compounds

Some P2X3 receptor antagonists have been developed as new therapeutic drugs for pain. We discovered a novel chemotype of P2X3 receptor antagonists with a pyrrolinone skeleton. Because of SAR studies to improve bioavailability of lead compound 2, compound (R)-24 was identified, which showed an analgesic effect against neuropathic pain by oral administration. We constructed a human P2X3 homology model as a template for the zebrafish P2X4 receptor, which agreed with SAR studies of pyrrolinone derivatives.     

多巴胺对吗啡成瘾大鼠海马区痛觉调制的研究进展

当今社会日益增长的吗啡等阿片类药物的非法滥用已经严重威胁到人类的健康。然而,迄今为止尚没有找到能够较为有效的防治阿片成瘾的方法。目前研究已知,阿片成瘾的形成所涉及的脑区及核团包括中脑腹侧被盖区(VTA)、伏隔核(NAc)、海马等,其成瘾涉及的神经递质系统包括多巴胺、5-羟色胺等。本文将就多巴胺及海马在痛觉调制及药物成瘾过程中的作用进行综述,为吗啡的成瘾与戒断的进一研究及治疗提供线索。     

小切口改良Mc Bride矫形术治疗足踇外翻畸形的临床疗效观察

目的:评估和总结使用小切口改良Mc Bride矫形术治疗足踇外翻畸形的临床疗效。方法:选择2010-2014年我院收治的明确诊断为踇外翻畸形的104例患者,所有患者均行小切口改良Mc Bride矫形术,观察和比较患者手术前和手术后3周、6个月时的VAS疼痛评分、踇外翻角测量(HVA)、跖骨间角测量(IMA)及足踝AOFAS评分。结果:所有患者均至少随访至术后6月,优良率为96.2%,患者术后3周、6月VAS评分、HVA与IMA的角度、AOFAS评分均较术前均明显改善,差异均具有统计学意义(P0.05)。仅3例患者在术后6个月时畸形复发,6例出现足部轻度疼痛,1例出现切口延迟愈合,余无明显并发症出现。结论:小切口改良Mc Bride矫形术能够有效纠正踇外翻畸形,并减轻患者的疼痛。     

6'-Guanidinonaltrindole (6'-GNTI) Is a G Protein-biased κ-Opioid Receptor Agonist That Inhibits Arrestin Recruitment

κ-Opioid receptor (KOR) agonists do not activate the reward pathway stimulated by morphine-like μ-opioid receptor (MOR) agonists and thus have been considered to be promising nonaddictive analgesics. However, KOR agonists produce other adverse effects, including dysphoria, diuresis, and constipation. The therapeutic promise of KOR agonists has nonetheless recently been revived by studies showing that their dysphoric effects require arrestin recruitment, whereas their analgesic effects do not. Moreover, KOR agonist-induced antinociceptive tolerance observed in vivo has also been proposed to be correlated to the ability to induce arrestin-dependent phosphorylation, desensitization, and internalization of the receptor. The discovery of functionally selective drugs that are therapeutically effective without the adverse effects triggered by the arrestin pathway is thus an important goal. We have identified such an extreme G protein-biased KOR compound, 6'-guanidinonaltrindole (6'-GNTI), a potent partial agonist at the KOR receptor for the G protein activation pathway that does not recruit arrestin. Indeed, 6'-GNTI functions as an antagonist to block the arrestin recruitment and KOR internalization induced by other nonbiased agonists. As an extremely G protein-biased KOR agonist, 6'-GNTI represents a promising lead compound in the search for nonaddictive opioid analgesic as its signaling profile suggests that it will be without the dysphoria and other adverse effects promoted by arrestin recruitment and its downstream signaling.