复方苦参注射液联合盐酸羟考酮缓释片治疗卵巢癌患者癌痛的临床研究

目的:探讨盐酸羟考酮缓释片联合复方苦参注射液对卵巢癌患者癌痛的影响。方法:选择我院2015年1月至2018年6月收治的77例卵巢癌患者,随机分为观察组(39例)及对照组(38例)。对照组给予羟考酮缓释片,观察组在对照组基础上加用复方苦参注射液,对比两组治疗前和治疗1个疗程后的疼痛数字评分(Numerical rating scale,NRS)评分和生活质量评分的变化,治疗期间每人每天的羟考酮用量及不良反应的发生情况。结果:治疗后,两组NRS评分均较治疗前明显下降,且观察组NRS评分明显低于对照组(P0.05)。治疗后,观察组的疲乏、恶心呕吐、疼痛、食欲丧失、便秘评分明显低于对照组(P0.05)。观察组每人每天羟考酮的用量、便秘及不良反应总发生率明显低于对照组(P0.05)。结论:复方苦参注射液联合羟考酮可有效缓解卵巢癌的癌痛,降低羟考酮毒副作用,提高患者的生活质量。     

Effect and mechanisms of sacral nerve stimulation on visceral hypersensitivity mediated by nerve growth factor

To investigate the efficacy of sacral nerve stimulation (SNS) on nerve growth factor (NGF) mediated visceral sensitivity in normal rat and visceral hypersensitivity model rats. 120 male newborn rats were randomly divided into 6 groups: group A was normal model group; group B ~ F were all sensitized with acetic acid enema and grouped again. Group c2 was given NGF antagonist, d2 group was given NGF agonist, e2 group was given PI3K inhibitor, and f2 group was given PLC‐γ inhibitor. After treatment, the expression of NGF, TrKA, PI3K, AKT, PLC‐γ, NF‐κB, TRPV1, pTRPV1 and intracellular Ca²⁺ content were detected. The expression of protein TRPV1 and pTRPV1 was increased, and Ca²⁺ was increased in the visceral hypersensitive group. NGF, TrKA in NGF antagonist group, PI3K, AKT, NF‐κB in PI3K inhibitor group, PLC‐γ in PLC‐γ inhibitor group were all almost not expressed. The relative expression of NGF, TrKA, PI3K, AKT, PLC‐γ and NF‐κB in NGF antagonist group was lower than that in visceral hypersensitivity group and NGF activator group (P < .01). The relative expression of NGF, TrKA, PI3K and AKT mRNA in NGF antagonist group was lower than that in the normal model group (P < .01). There was no significant difference in the relative expression of PLC‐γ and NF‐κB mRNA (P > .05). The expression level of MAPK, ERK1 and ERK2 in visceral hypersensitivity group was higher than that in PI3K inhibitor group and PLC‐γ inhibitor group. The normal group Ca²⁺ curve was flat, and the NGF agonist group had the highest Ca²⁺ curve peak. Calcium concentration in visceral hypersensitivity group was higher than that in PI3K inhibitor group and that in PLC‐γ inhibitor group was higher than that in NGF antagonist group. The binding of TrkA receptor to NGF activates the MAPK/ERK pathway, the PI3K/Akt pathway and the PLC‐γ pathway, causing changes in the fluidity of intracellular and extracellular Ca²⁺, resulting in increased sensitivity of visceral tissues and organs.     

Modulation of social behavior and dominance status by chronic pain in mice

The potential influence of pain on social behavior in laboratory animals has rarely been evaluated. Using a new assay of social behavior, the tube co‐occupancy test (TCOT), we assess propinquity—the tendency to maintain close physical proximity—in mice exposed to pain using subcutaneous zymosan or spared nerve injury as noxious stimuli. Our previous experience with the TCOT showed that outbred mouse sibling dyads show higher levels of tube co‐occupancy than stranger dyads. We find here that long‐lasting pain from spared nerve injury given to both mice in the dyad abolishes this effect of familiarity, such that strangers also display high levels of propinquity. We performed a separate experiment to assess the effect on dominance behavior of nerve injury to one or both mice of a dyad in which relative dominance status had been previously established via the confrontation tube test. We find that neuropathic pain given only to the dominant mouse reverses the relationship in male but not female mice, such that the previously subordinate mouse becomes dominant. These observations bolster the scant but growing evidence that pain can robustly affect social behavior in animals.     

Analgesic effect of Photobiomodulation Therapy: An in vitro and in vivo study

Laser therapy, also known as Photobiomodulation (PBM) is indicated to reduce pain associated with different pathologies and applied using protocols that vary in wavelength, irradiance and fluence. Its mechanisms of action are still unclear and possibly able to directly impact on pain transmission, reducing nociceptor response. In our study, we examined the effect of two specific laser wavelengths, 800 and 970 nm, extensively applied in the clinical context and known to exert important analgesic effects. Our results point to mitochondria as the primary target of laser light in isolated dorsal root ganglion (DRG) neurons, reducing adenosine triphosphate content and increasing reactive oxygen species levels. Specifically, the 800 nm laser wavelength induced mitochondrial dysregulation, that is, increased superoxide generation and mitochondrial membrane potential. When DRG neurons were firstly illuminated by the different laser protocols and then stimulated with the natural transient receptor potential cation channel subfamily V member 1 (TRPV1) ligand capsaicin, only the 970 nm wavelength reduced the calcium response, in both amplitude and frequency. Consistent results were obtained in vivo in mice, by subcutaneous injection of capsaicin. Our findings demonstrate that the effect of PBM depends on the wavelength used, with 800 nm light mainly acting on mitochondrial metabolism and 970 nm light on nociceptive signal transmission.     

Analyzing the role of cannabinoids as modulators of Wnt/β-catenin signaling pathway for their use in the management of neuropathic pain

Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/β-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1–6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/β-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/β-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/β-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.     

Responsibility and the sense of agency enhance empathy for pain

Being held responsible for our actions strongly determines our moral judgements and decisions. This study examined whether responsibility also influences our affective reaction to others'' emotions. We conducted two experiments in order to assess the effect of responsibility and of a sense of agency (the conscious feeling of controlling an action) on the empathic response to pain. In both experiments, participants were presented with video clips showing an actor''s facial expression of pain of varying intensity. The empathic response was assessed with behavioural (pain intensity estimation from facial expressions and unpleasantness for the observer ratings) and electrophysiological measures (facial electromyography). Experiment 1 showed enhanced empathic response (increased unpleasantness for the observer and facial electromyography responses) as participants'' degree of responsibility for the actor''s pain increased. This effect was mainly accounted for by the decisional component of responsibility (compared with the execution component). In addition, experiment 2 found that participants'' unpleasantness rating also increased when they had a sense of agency over the pain, while controlling for decision and execution processes. The findings suggest that increased empathy induced by responsibility and a sense of agency may play a role in regulating our moral conduct.     

布拉氏酵母菌联合加味逍遥散治疗小儿功能性再发性腹痛的临床疗及安全性

目的观察布拉氏酵母菌联合加味逍遥散治疗小儿功能性再发性腹痛(Recurrent abdominal pain,RAP)的临床疗效和安全性。方法将66例5~14岁RAP患儿随机分为治疗组和对照组各33例,2组腹痛发作时适当应用解痉剂及对症处理。治疗组用加味逍遥散水煎服,每天一剂,分3次口服;联合布拉氏酵母菌250 mg/次,每天2次口服。对照组单独用加味逍遥散(用法同上),2周为一个疗程。结果治疗组显效率与总有效率明显高于对照组(P0.05)。结论布拉氏酵母菌联合加味逍遥散治疗儿童RAP疗效确切,不良反应小,依从性好。     

Kv3.4 channel function and dysfunction in nociceptors

Recently, we reported the isolation of the Kv3.4 current in dorsal root ganglion (DRG) neurons and described dysregulation of this current in a spinal cord injury (SCI) model of chronic pain. These studies strongly suggest that rat Kv3.4 channels are major regulators of excitability in DRG neurons from pups and adult females, where they help determine action potential (AP) repolarization and spiking properties. Here, we characterized the Kv3.4 current in rat DRG neurons from adult males and show that it transfers 40–70% of the total repolarizing charge during the AP across all ages and sexes. Following SCI, we also found remodeling of the repolarizing currents during the AP. In the light of these studies, homomeric Kv3.4 channels expressed in DRG nociceptors are emerging novel targets that may help develop new approaches to treat neuropathic pain.     

Ion channel therapeutics for pain

Pain is a complex disease which can progress into a debilitating condition. The effective treatment of pain remains a challenge as current therapies often lack the desired level of efficacy or tolerability. One therapeutic avenue, the modulation of ion channel signaling by small molecules, has shown the ability to treat pain. However, of the 215 ion channels that exist in the human genome, with 85 ion channels having a strong literature link to pain, only a small number of these channels have been successfully drugged for pain. The focus of future research will be to fully explore the possibilities surrounding these unexplored ion channels. Toward this end, a greater understanding of ion channel modulation will be the greatest tool we have in developing the next generation of drugs for the treatment of pain.