Sensory neuron regulation of gastrointestinal inflammation and bacterial host defence

Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage. Emerging evidence shows that sensory neurons participate in host–microbe interactions. Sensory neurons are able to detect pathogenic and commensal bacteria through specific metabolites, cell‐wall components, and toxins. Here, we review recent work on the mechanisms of bacterial detection by distinct subtypes of gut‐innervating sensory neurons. Upon activation, sensory neurons communicate to the immune system to modulate tissue inflammation through antidromic signalling and efferent neural circuits. We discuss how this neuro‐immune regulation is orchestrated through transient receptor potential ion channels and sensory neuropeptides including substance P, calcitonin gene‐related peptide, vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide. Recent studies also highlight a role for sensory neurons in regulating host defence against enteric bacterial pathogens including Salmonella typhimurium, Citrobacter rodentium and enterotoxigenic Escherichia coli. Understanding how sensory neurons respond to gastrointestinal flora and communicate with immune cells to regulate host defence enhances our knowledge of host physiology and may form the basis for new approaches to treat gastrointestinal diseases.     

基于Peplau人际关系模式的家庭访视在肺癌晚期疼痛患者中的应用效果分析

目的 探讨基于Peplau人际关系模式的家庭访视在肺癌晚期疼痛患者中的应用效果.方法 选取肺癌晚期疼痛患者70例,采用随机数字表法分为对照组(n=35)和观察家庭组(n=35).对照组患者应用常规护理方法,观察组患者在常规护理基础上运用Peplau人际关系模式对患者进行访视.于访视4周后进行自我护理能力和疼痛缓解程度的比较.结果 观察组患者的自护技能、自护责任感、自我概念及健康知识评分均明显高于对照组(P﹤0.0001);观察组患者疼痛缓解率为94.29％,高于对照组的74.29％,差异有统计学意义(P﹤0.05).结论 基于Peplau人际关系模式的家庭访视可提高肺癌晚期疼痛患者自我护理能力,增强疼痛治疗效果,值得临床推广应用.     

A Comprehensive Functional Analysis of NTRK1 Missense Mutations Causing Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV)

Hereditary sensory and autonomic neuropathy type IV (HSAN IV) is an autosomal recessive disorder characterized by a complete lack of pain perception and anhidrosis. Here, we studied a cohort of seven patients with HSAN IV and describe a comprehensive functional analysis of seven novel NTRK1 missense mutations, c.1550G >A, c.1565G >A, c.1970T >C, c.2096T >C, c.2254T >A, c.2288G >C, and c.2311C >T, corresponding to p.G517E, p.G522E, p.L657P, p.I699T, p.C752S, p.C763S, and p.R771C, all of which were predicted pathogenic by in silico analysis. The results allowed us to assess the pathogenicity of each mutation and to gain novel insights into tropomyosin receptor kinase A (TRKA) downstream signaling. Each mutation was systematically analyzed for TRKA glycosylation states, intracellular and cell membrane expression patterns, nerve growth factor stimulated TRKA autophosphorylation, TRKA‐Y496 phosphorylation, PLCγ activity, and neurite outgrowth. We showed a diverse range of functional effects: one mutation appeared fully functional, another had partial activity in all assays, one mutation affected only the PLCγ pathway and four mutations were proved null in all assays. Thus, we conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism underlying HSAN IV. By corollary, the assessment of the clinical pathogenicity of HSAN IV mutations is more complex than initially predicted and requires a multifaceted approach.     

Combination of Exercise and Acupuncture Versus Acupuncture Alone for Treatment of Myofascial Pain Syndrome: A Randomized Clinical Trial

Myofascial pain syndrome (MPS) is a common musculoskeletal disorder. This study was designed to compare the effects of aerobic exercise plus acupuncture with acupuncture alone in treatment of patients with MPS. Sixty-four patients (55 female and 9 male) with MPS in their neck and shoulders participated in the study with mean age of 33.1 ± 6.4 years. Participants were randomly allocated to aerobic exercise plus acupuncture (n = 32) or acupuncture alone (n = 32) groups. Outcome measurements included visual analog scale, pressure pain threshold, neck disability index, and quality of life that was measured with QoL-SF36 scale. Each group received 10 sessions of acupuncture in combination with aerobic exercise or acupuncture alone. The outcome measures were evaluated at baseline, at the end of the last treatment session, and at 1-month follow-up visit. While participants were waiting for their 1-month follow-up visit, the patients who received combination therapy were asked to continue their aerobic exercise by jogging 40 minutes a day. Although mean visual analog scale, pressure pain threshold, neck disability index, and QoL-SF36 were significantly improved in both groups (p < 0.001), there was no statistically significant difference among the measures between the two groups throughout the evaluated sessions. The interaction effect of time and groups did not show any significant difference among the outcome measures (p > 0.29).     

Neurosurgery of epilepsy,movement disorders and pain

Functional neurosurgery involves the surgical management of a wide range of neurological diseases with the aim of treating conditions such as movement disorders, spasticity, epilepsy and intractable pain. Functional neurosurgery began with ablative surgical techniques involving destruction of neural structures responsible for the aberrant neural pathways/networks causing pathology. In more recent years there has been a move away from the creation of permanent destructive lesions towards modulation of the neural networks utilizing neuromodulation. Neuromodulation therapies include invasive (e.g. deep brain stimulators, cortical stimulators, vagal nerve stimulators and spinal cord stimulators) and non-invasive (e.g. transcranial magnetic stimulation) approaches that involve the application of electrical stimulation to drive or inhibit neural function within a circuit. Most implantable neuromodulation systems include three primary components: stimulating electrode(s) with contacts at the tip through which electricity is delivered; an implantable pulse generator (IPG) that serves as a signal generator/battery pack; and the extension cable(s) to subcutaneously connect the electrode(s) to the IPG. In this article we primarily focus on the current role of neuromodulation in treating movement disorders, epilepsy and pain, and also consider emerging and evolving applications.