Therapeutic Strategies for Postherpetic Neuralgia: Mechanisms, Treatments, and Perspectives.

PURPOSE OF REVIEW: Postherpetic neuralgia is an annoying pain that mainly affects older people. In order to give patients more options, this review summarizes the pharmacological and interventional treatments for postherpetic neuralgia and updates the research on the efficacy, thereby providing doctors with more treatment options. The adverse effects and effective doses of its various treatments are also presented so that the therapy can be prescribed according to their concrete physical conditions. In a word, this review is dedicated to providing a comprehensive overview of the treatment options for postherpetic neuralgia and offering patients more choices. RECENT FINDINGS: Combinational therapy is more excellent than monotherapy. The local anesthesia and gabapentin comprised outstanding compatibility. In addition, two therapeutic tools for PHN patients, especially for the intractable ones, electroacupuncture (EA), and osteopathic manipulative treatment (OMT), show their efficacy and become potential options to alleviate pain. In terms of treatment, guidelines recommend patients use tricyclic antidepressants (TCAs), gabapentin, pregabalin, and 5% lidocaine patches as the first-line medications, and gabapentin is investigated most, especially the gabapentin enacarbil (GEn). And drug efficacy can be limited by adverse effects and tolerated doses. Interventional treatments, with their invasiveness and operational difficulty, are usually considered for intractable patients. Combinational therapies may be used when a single therapy cannot achieve the desired effect. Therapies such as OMT and EA have also been proposed to palliate pain in some cases, and future directions of treatment may be investigated in Chinese medicine and acupuncture.

Treatment modalities in brachioradial pruritis: a systematic review.

INTRODUCTION: Brachioradial pruritis is a rare dysesthesia syndrome that is known to negatively impact quality of life. No consensus exists regarding optimal treatment strategies. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Collaboration Clinical Trials Registry from 1966 to 2021 for studies using the title word "brachioradial pruritis" with no language restriction. One author (A.Z.) screened and performed full article reviews of all randomized clinical trials, cohort studies, case-control studies, case reports, and case series describing treatment outcomes among patients with brachioradial pruritis. RESULTS: We identified 239 potential articles with a final set of 45 articles meeting inclusion criteria. Only a single randomized clinical trial was identified, finding no significant benefit of topical capsaicin cream. Treatment modalities with the greatest number of reported successful therapeutic trials include gabapentin and tricyclic antidepressants. In patients with confirmed cervical spine disease, spine-directed therapies such as epidural injections were found to be beneficial. Case reports and small case series describing less-common treatments were also identified. DISCUSSION: The literature is overall limited with the greatest support for gabapentin, pregabalin, tricyclic antidepressants, and spine-directed therapies in appropriate patients with brachioradial pruritis. Future randomized clinical trials are needed to compare the relative effectiveness of available treatments.

Monitoramento do horizonte tecnológico: Medicamentos para o tratamento do transtorno depressivo maior / Monitoring the technological horizon: Drugs for the treatment of major depressive disorder

A DOENÇA: O transtorno depressivo maior (TDM) é considerado um grave problema de saúde pública que afeta mais de 264 milhões de pessoas em todo o mundo (1). No Brasil, a prevalência nacional da depressão estimada pelo Global Burden of Disease 2017 foi de 3,3% e esta condição está entre as quatro principais causas de invalidez, afetando a produtividade e qualidade de vida dos pacientes. Nas populações vulneráveis como os idosos, esse número é significativamente maior, uma revisão sistemática publicada em 2019 estimou uma prevalência de 21,9% em idosos brasileiros residentes na comunidade. Segundo projeções da Organização Mundial da Saúde (OMS) para 2030, a depressão ocuparia o primeiro lugar entre as principais doenças incapacitantes. TRATAMENTO RECOMENDADO: Atualmente não existem Protocolos Clínicos e Diretrizes Terapêuticas (PCDT) do Ministério da Saúde, bem como avaliações da Conitec sobre esse tema. O tratamento da TDM depende da gravidade da doença, nos indivíduos com depressão grave, em que há risco de suicídio, o encaminhamento para o especialista deve ser imediato e a hospitalização pode ser um recurso necessário. Nos casos moderados, em geral, se sugere a combinação de psicoterapia e medicamentos antidepressivos, sendo que diversas classes são consideradas opções terapêuticas, como Inibidores seletivos da recaptação da serotonina; Inibidores seletivos da recaptação da noradrenalina; Antidepressivos atípicos; Moduladores da serotonina; Antidepressivos tricíclicos; Inibidores da monoaminoxidase. ESTRATÉGIA DE BUSCA: Uma busca no repositório de protocolos de estudos clínicos ClinicalTrials.gov foi realizada com o objetivo de localizar os medicamentos em fase de pesquisa clínica e/ou recentemente aprovados para TDM. Foram excluídos medicamentos com registro na Anvisa superior a dois anos para a indicação de depressão maior, assim como procedimentos, produtos da medicina tradicional chinesa, vitaminas e testes diagnósticos. MEDICAMENTOS APROVADOS RECENTEMENTE: ESCETAMINA SPRAY NASAL: A escetamina, o enantiômero "S" da cetamina racêmica, é um antagonista não seletivo, não competitivo do receptor N-metil-D-aspartato (NMDA), que atua como um modulador do receptor de glutamato, o que parece aumentar a sinalização entre as células, restaurando a função normal nas regiões cerebrais. Embora a ligação da escetamina ao receptor NMDA aumente o glutamato do sistema nervoso central (SNC), o mecanismo de ação exato como antidepressivo permanece incerto. Esse medicamento possui registro nas agências norte-americana e europeia (FDA e EMA) e, em dezembro de 2020, foi aprovado pela Anvisa para tratamento do TDM em pacientes com ideação suicida e de depressão resistente ao tratamento. Depressão resistente ao tratamento: MEDICAMENTOS EM FASE DE PESQUISA CLÍNICA: RAPASTINEL: O rapastinel (GLYX-13) é um anticorpo monoclonal com apresentação para administração endovenosa, que atua como agonista parcial funcional do receptor de N-metil-D-aspartato (NMDA) com ação no sistema glutamatérgico. INFORMAÇÕES ADICIONAIS: Atualmente existem diferentes tecnologias sendo estudadas para o tratamento de TDM, sendo que neste informe, foram descritas as tecnologias que estão em um horizonte mais próximo para aprovação por agências regulatórias ou foram aprovadas pela Anvisa recentemente. A escetamina spray nasal e brexpiprazol foram aprovados pela Anvisa em 2020, com o objetivo de avaliar a incorporação dessas tecnologias no mundo, uma busca foi realizada em novembro de 2021 nos websites das agências de ATS do Reino Unido, Canadá e Austrália. CONSIDERAÇÕES FINAIS O TDM: é um grave problema de saúde pública por afetar milhões de pessoas em todo o mundo. Apesar de haver muitos estudos em andamento para o tratamento dessa condição clínica, em geral os resultados dos estudos demonstraram que não há diferença significativa na eficácia dos medicamentos quando comparados ao placebo. O rapastinel, que recebeu designação Breakthough Therapy pela FDA em 2016, caracterizando-o como medicamento inovador para uma necessidade médica não atendida e que teria prioridade para avaliação na FDA, apresentou resultados promissores para estudo de fase 2, entretanto eles não foram confirmados nos ECR fase 3, duplo-cego, controlados por placebo, tanto em monoterapia como tratamento adjuvante para TDM. O medicamento REL-1017 (ou d-metadona), também é um inibidor do receptor NMDA e recebeu designação FastTrack pela FDA em 2017 para o tratamento adjuvante de TDM. Apesar dos dados do estudo de fase 2 mostrarem resultados promissores, o estudo de fase 3 ainda está em andamento. Também, esperam-se os dados das diversas pesquisas fase 3, realizadas em diferentes cenários (adjuvante ou monoterapia, por exemplo), e que avaliaram o medicamento SAGE-217, um modulador do receptor GABA que mostrou resultados positivos no estudo fase 2. O brexpiprazol foi aprovado pela Anvisa em 2020, indicado para o tratamento de depressão maior em adultos em associação a um antidepressivo, em caso de inefetividade da monoterapia com antidepressivo anterior. Os ensaios clínicos randomizados fase 3 avaliaram que o uso do medicamento reduziu o escore basal de MADRS na semana 6. O brexipiprazol para tratamento de depressão não foi avaliado por nenhuma agência de ATS até o momento. A escetamina spray nasal teve registro sanitário aprovado pela Anvisa em novembro de 2020 para pacientes com ideação suicida e de depressão resistente ao tratamento - a partir da avaliação da redução do escore basal de MADRS em 24h e após 28 dias. Mas esse medicamento não foi recomendado para incorporação pelas agências de ATS do Reino Unido e Canadá. Os medicamentos em desenvolvimento para depressão incluem populações específicas e frequentemente são usados em associação a outros antidepressivos. O tratamento da depressão grave e não responsiva a tratamentos prévios ainda é uma necessidade médica não atendida, assim como tratamentos específicos para populações vulneráveis como idosos. Também é importante destacar que todos os resultados descritos neste documento são dados precoces e devem ser avaliados com cautela. Dessa maneira, considerando os estudos de fase 3 citados neste documento, conclui-se que ainda são poucas as opções promissoras em estudo para um horizonte de curto a médio prazo.

Synergistic effect between imipramine and citicoline upon induction of analgesic and antidepressant effects in mice.

Imipramine is a tricyclic antidepressant (TCA) drug that is sometimes used to treat neuropathic pain. Citicoline is a dietary supplement that has been used as a neuroprotective agent for neurological disorders. Probable interaction between imipramine and citicoline on pain and depression behaviors was examined in mice using a tail-flick test, open field test (OFT), forced swimming test (FST), and tail suspension test (TST). The results indicated that the intraperitoneal (i.p.) administration of citicoline (50 mg/kg) induced analgesic and antidepressant-like behaviors in mice. Similarly, i.p. injection of imipramine (5 mg/kg) induced dose-dependent anti-nociceptive and anti-depressive effects. Co-administration of different doses of imipramine (1.25, 2.5, and 5 mg/kg) along with an ineffective dose of citicoline (6.25 mg/kg) increased tail-flick latency and decreased immobility time in the FST, suggesting an analgesic and antidepressant-like behaviors. Interestingly, there is a synergistic effect between imipramine and citicoline upon the induction of analgesic and antidepressant effects. All doses of the drugs had no significant effect on the locomotor activity. Based on these results, it can be concluded that the administration of citicoline (as an adjuvant drug) in combination with imipramine increased the efficacy of TCA drugs for modulation of pain and depression behaviors.

Panic disorder: A review of treatment options.

BACKGROUND: Panic disorder (PD) is a devastating illness, with numerous patients experiencing significant functional disability and many not achieving full remission with first-line pharmacologic and psychotherapeutic treatments. METHODS: A search of PubMed, Cochrane Library, and PsychINFO databases was used to identify publications focused on evidence-based treatment of PD. RESULTS: Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are standard first-line pharmacologic treatments for PD. Many other antidepressants can be considered as alternatives to SSRIs, including serotonin-norepinephrine reuptake inhibitors, serotonin multimodal agents, tricyclic antidepressants, monoamine oxidase inhibitors, and mirtazapine. Certain anticonvulsants and antipsychotics may be helpful; however, the evidence base is limited. Buspirone, beta blockers, and hydroxyzine can be considered third-line agents. Currently, there is minimal data supporting the use of electroconvulsive therapy or repetitive transcranial magnetic stimulation (rTMS). There is very little evidence justifying the use of medical cannabis or over-the-counter supplements for PD, and these treatments have risk for adverse effects. Research strongly supports the use of cognitive-behavioral therapy (CBT) for PD. CONCLUSIONS: Many options exist for the management of PD. Treatments with the strongest evidence include SSRIs, other antidepressants, and CBT. Newer interventions approved for the treatment of depression, such as serotonin multimodal agents, esketamine, and rTMS, merit further investigation for use in PD.

Acupuncture for the Management of Low Back Pain.

PURPOSE OF REVIEW: This evidence-based systematic review will focus on the use of acupuncture and its role in the treatment of low back pain to help better guide physicians in their practice. It will cover the background and the burden of low back pain and present the current options for treatment and weigh the evidence that is available to support acupuncture as a treatment modality for low back pain. RECENT FINDINGS: Low back pain (LBP), defined as a disorder of the lumbosacral spine and categorized as acute, subacute, or chronic, can be a debilitating condition for many patients. Chronic LBP is more typically defined by its chronicity with pain persisting > 12 weeks in duration. Conventional treatment for chronic LBP includes both pharmacologic and non-pharmacologic options. First-line pharmacologic therapy involves the use of NSAIDs, then SNRI/TCA/skeletal muscle relaxants, and antiepileptics. Surgery is usually not recommended for chronic non-specific LBP patients. According to the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain and the 2017 American College of Physicians (ACP) clinical practice guidelines for chronic pain, non-pharmacologic interventions, acupuncture can be a first-line treatment for patients suffering from chronic low back pain. Many studies have been done, and most show promising results for acupuncture as an alternative treatment for low back pain. Due to non-standardized methods for acupuncture with many variations, standardization remains a challenge.

[Rational treatment of patients with functional dyspepsia].

Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.

Update on Indigestion.

Dyspepsia affects a large percentage of the general population and can lead to lost work productivity and reduced quality of life. Patients with dyspepsia younger than 60 should not routinely undergo endoscopy but instead should pursue Helicobacter pylori test-and-treat approach. For patients 60 and older, endoscopy should be performed. Patients without any identifiable cause for their symptoms are diagnosed with functional dyspepsia. Guideline-based treatment includes H pylori eradication and proton pump inhibitor use. If acid suppression is not adequate, treatment with a tricyclic antidepressant followed by a prokinetic agent and psychological therapy are considered. Complementary therapies are not recommended due to limited evidence.

Pain management in hidradenitis suppurativa and a proposed treatment algorithm.

Pain contributes substantially to reduced quality of life in individuals living with hidradenitis suppurativa (HS). Although improved understanding of HS pathogenesis and treatment has resulted in improved evidence-based HS management guidelines, comprehensive pain management guidelines have yet to be developed. Few HS-specific data exist to guide pharmacologic analgesia; however, recognizing HS pain as either acute or chronic and predominantly nociceptive (aching and gnawing pain due to tissue damage) versus neuropathic (burning-type pain due to somatosensory nervous system dysfunction) provides a conceptual framework for applying outside pain management practices to HS management. This article incorporates the best available evidence from the HS and pain literature to propose an HS pain algorithm that integrates psychological, pharmacologic, and complementary and alternative treatment modalities.

To Be Continued? Long-Term Treatment Effects of Antidepressant Drug Classes and Individual Antidepressants on the Risk of Developing Dementia: A German Case-Control Study.

BACKGROUND: Given the need for disease-modifying therapies for dementia, drug repurposing appears to be a promising approach, at least as a risk reduction treatment. Preclinical studies suggest that antidepressants-in particular selective serotonin reuptake inhibitors-have beneficial effects on dementia-related biomarkers and functional outcomes, although clinical data are inconclusive. The present case-control study aimed to evaluate the effects of antidepressant drug classes and individual compounds with different treatment durations on the risk of developing dementia. METHODS: Analyses are based on data from the German Disease Analyzer database (owned and maintained by IQVIA) and included 62,317 subjects with an incident dementia diagnosis (ICD-10: F01, F03, G30, F06.7) and controls matched by age, sex, and physician between January 2013 and December 2017. Logistic regression analyses adjusting for health insurance status and comorbid diseases associated with dementia or antidepressant use were performed to investigate the association between dementia incidence and treatment with 4 major antidepressant drug classes and 14 of the most frequently prescribed individual substances. RESULTS: In 17 of 18 comparisons, long-term treatment (≥ 2 years) with any antidepressant was associated with a lower incidence of dementia than short-term treatment. Tricyclic and herbal antidepressants were associated with a decrease in dementia incidence, especially with long-term treatment. The lowest risks for dementia on an individual substance basis were identified for long-term treatment with escitalopram (odds ratio [OR] = 0.66; 95% CI, 0.50-0.89) and Hypericum perforatum (OR = 0.6; 95% CI, 0.51-0.70). CONCLUSIONS: Long-term treatment with tricyclic antidepressants, Hypericum perforatum, or escitalopram may be associated with reduced incidence of dementia. If antidepressant therapy is well tolerated, continuation-even if depressive symptoms have resolved-may be considered even beyond the purpose of relapse prevention. Future combined analyses of multinational registries and long-term clinical trials are needed to substantiate these findings.

A Comprehensive Review of the Diagnosis, Treatment, and Management of Postmastectomy Pain Syndrome.

PURPOSE OF REVIEW: Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy. RECENT FINDINGS: The underlying pathophysiology is likely multifactorial, although exact mechanisms have yet to be elucidated. In this regard, neuralgia of the intercostobrachial nerve is currently implicated as the most common cause of PMPS. Numerous pharmacological options are available in the treatment of PMPS, including gabapentinoids, tricyclic antidepressants, selective serotonin reuptake inhibitors, NMDA receptor antagonists, and nefopam (a non-opioid, non-steroidal benzoxazocine analgesic). Minimally invasive interventional treatment including injection therapy, regional anesthesia, botulinum toxin, and neuromodulation has been demonstrated to have some beneficial effect. A comprehensive update highlighting current perspectives on the treatment of postmastectomy pain syndrome is presented with emphasis on treatments currently available and newer therapeutics currently being evaluated to alleviate this complex and multifactorial condition.

A Comprehensive Review of the Treatment and Management of Myofascial Pain Syndrome.

PURPOSE OF REVIEW: Myofascial pain syndrome (MPS) is a musculoskeletal pain condition that stems from localized, taut regions of skeletal muscle and fascia, termed trigger points. The purpose of this comprehensive review is to provide updated information on prevalence, pathophysiology, and treatment modalities with a focus on interventional modalities in managing MPS. RECENT FINDINGS: Though MPS can present acutely, it frequently presents as a chronic condition, affecting up to 85% of adults during their lifetime. MPS is an often-overlooked component of pain with overarching effects on society, including patient quality of life, physical and social functioning, emotional well-being, energy, and costs on health care. The prevalence of MPS is generally increased among patients with other chronic pain disorders and has been associated with various other conditions such as bladder pain syndrome, endometriosis, and anxiety. MPS is poorly understood and remains a challenging condition to treat. Non-pharmacologic treatment modalities such as acupuncture, massage, transcutaneous electrical stimulation, and interferential current therapy may offer relief to some patients with MPS. Additional studies are warranted to get a better understanding of managing myofascial pain.

Gastroparesis: New insights into an old disease.

Gastroparesis (Gp) is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction. Although this condition has been reported in the literature since the mid-1900s, only recently has there been renewed clinical and scientific interest in this disease, which has a potentially great impact on the quality of life. The aim of this review is to explore the pathophysiological, diagnostic and therapeutical aspects of Gp according to the most recent evidence. A comprehensive online search for Gp was carried out using MEDLINE and EMBASE. Gp is the result of neuromuscular abnormalities of the gastric motor function. There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes. As regards diagnostic approach, 99-Technetium scintigraphy is currently considered to be the gold standard for Gp. Its limits are a lack of standardization and a mild risk of radiation exposure. The C13 breath testing is a valid and safe alternative method. 13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits. The wireless motility capsule is a promising technique, but its use is limited by costs and scarce availability in many countries. Finally, therapeutic strategies are related to the clinical severity of Gp. In mild and moderate Gp, dietary modification and prokinetic agents are generally sufficient. Metoclopramide is the only drug approved by the Food and Drug Administration for Gp. However, other older and new prokinetics and antiemetics can be considered. As a second-line therapy, tricyclic antidepressants and cannabinoids have been proposed. In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed. In drug-unresponsive Gp patients some alternative strategies (endoscopic, electric stimulation or surgery) are available.

Outcomes of Treating Rumination Syndrome with a Tricyclic Antidepressant and Diaphragmatic Breathing.

BACKGROUND: Rumination syndrome is a functional gastrointestinal disorder characterized by effortless postprandial regurgitation and accompanied by gastric visceral hypersensitivity. Almost invariably, the onset of symptoms is preceded by a psychologically stressful situation, and anxiety is often an accompanying complaint. In this background of gastric visceral hypersensitivity, anxiety and psychological stress, we investigated the effectiveness of combining a tricyclic antidepressant (TCA) with diaphragmatic breathing/relaxation techniques for the treatment of rumination syndrome. MATERIALS AND METHODS: Patients who fulfilled the Rome IV criteria for rumination syndrome received hands-on instructions and/or coaching on diaphragmatic breathing techniques, were given relaxing auditory media, started on a TCA, and completed a follow-up symptoms questionnaire after undergoing a minimum of 3 months of this therapy. RESULTS: A total of 44 patients, 35 women; mean age 40.4 (range 20-71) were identified. Mean time from onset of symptoms to diagnosis was 36.0 months (range 6-180). Weight loss ranged from 1.4 to 39.5 kg. Approximately 65.9% had a history of anxiety and/or depression, and a separate 65.9% reported the onset of symptoms were chronologically related to an inciting event and/or psychological stressor. After a mean follow-up period of 8.8 months, 90.9% of patients reported improvement in their symptoms, with a mean subjective improvement from baseline of 68.9%, and specifically, 45.5% of patients reported ≥80% improvement. Weight increased or stabilized in 80.6% of those initially reporting weight loss. CONCLUSIONS: The combination of a TCA with diaphragmatic breathing/relaxation techniques is an effective treatment modality for the management of rumination syndrome as it addresses the underlying factors identified in this entity.

Preliminary Biochemical Description of Brain Oxidative Stress Status in Irritable Bowel Syndrome Contention-Stress Rat Model.

Background and objectives: Oxidative stress and inflammation have been implicated in the etiology of irritable bowel syndrome (IBS), a common gastrointestinal functional disease. This study aimed to further characterize the contention-stress rat model by exploring a possible correlation between oxidative stress markers measured in brain tissues with behavioral components of the aforementioned model. Thus, it is hereby proposed a possible IBS animal model relevant to pharmacological and complementary medicine studies. Materials and Methods: Wild-type male Wistar rats (n = 5/group) were chronically exposed to 6-hour/day contention, consisting of isolating the animals in small, vital space-granting plastic devices, for seven consecutive days. Following contention exposure, temporal lobes were extracted and subjected to biochemical analyses to assess oxidative stress-status parameters. Results: Our results show increased brain oxidative stress in contention-stress rat model: decreased superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde production in the IBS group, as compared to the control group. Furthermore, the biochemical ratios which are used to evaluate the effectiveness of an antioxidant system on oxidative stress could be described in this model. Conclusions: The correlations between the behavioral patterns and biochemical oxidative stress features could suggest that this may be a complex model, which can successfully mimic IBS symptomatology further providing evidence of a strong connection between the digestive system, enteric nervous system, and the central nervous system.

Clinical Pearls on Sleep Management in Atopic Dermatitis.

Multiple etiologies contribute to sleep disturbance in atopic dermatitis (AD) patients, including learned scratching behavior and increased monoamines, cutaneous blood flow, inflammatory cell activities, and cytokines, as well as decreased melatonin, anti-inflammatory cytokines, and skin barrier function. Insomnia impairs cognitive development in children with AD, leading to behavioral problems and learning disabilities. Insomnia in adults with AD impedes work productivity. In this article, we discuss pearls on improving insomnia through both nonpharmacologic modalities, such as environmental adjustments and massage therapy, and pharmaceutical approaches including melatonin, antihistamines, tricyclic antidepressants, mirtazapine, and benzodiazepine and nonbenzodiazepine sedatives. Future investigations should further delineate the mechanistic link between insomnia and AD exacerbation and identify strategies to combat sleep-related disease burden.

Up-date on Clinical Management of Postherpetic Neuralgia and Mechanism-Based Treatment: New Options in Therapy.

Patients with postherpetic neuralgia may experience various sensory signs and symptoms of pain. Despite this, the recommendations for medicinal treatment do not differ accordingly. In order to find the appropriate treatment options for postherpetic neuralgia, several attempts have been made in the past. The crucial obstacle to these attempts was insufficient or no subgrouping of patients according to their sensory phenotype, mostly resulting in an unsatisfactory treatment response. Recently, a new concept of retrospective stratification according to the patients' sensory phenotype has been made in a large cohort of pain patients. This new stratification tool allows a predictive validity for treatment response in subgroups of patients and might be of potential value in determining the optimal treatment in postherpetic neuralgia patients.

An evaluation of the pharmacotherapy for interstitial cystitis.

INTRODUCTION: Interstitial cystitis (IC) and bladder pain syndrome (BPS) are chronic conditions that can be debilitating for patients. There is no consensus as to their etiology, and there are many proposed treatment algorithms. Oftentimes multimodal therapy, such as combining behavioral modification and physical therapy alongside pharmacotherapies, will be utilized. With the various treatment options available to patients and providers, there is an ever-growing need to implement evidence-based therapies. AREAS COVERED: The authors explore the different pharmacotherapies as commonly recommended in the American Urological Association (AUA) and European Association of Urology (EAU) multitiered guidelines for IC/BPS treatment as well as other investigational therapies. Pharmacotherapies targeting bladder, pelvic, and/or systemic factors in the overall treatment of IC/BPS are discussed with a particular focus on evidence-based guideline therapies. This article also looks at emerging therapies of interest. EXPERT OPINION: IC/BPS is a syndrome that requires a multimodal approach, including clinical phenotyping and directed therapy based on the patient's symptoms. The AUA and EAU provide guidelines for practitioners to follow, but adequate treatment requires the therapy to be targeted toward the patient's phenotypic domain.

Distal Esophageal Spasm: A Review.

Distal esophageal spasm is a rare motility disorder presenting principally with nonobstructive dysphagia and noncardiac chest pain. In symptomatic patients, the manometric diagnosis is made when >10% of the wet swallows have simultaneous and/or premature contractions intermixed with normal peristalsis. We characterize manometry and barium as complementary diagnostic approaches, and given the intermittent nature of the disorder, one should be always aware that it is almost impossible to rule out spasm. Treatment is difficult; we propose an approach beginning with the least invasive intervention.

Recurrent Abdominal Pain in Children: Summary Evidence From 3 Systematic Reviews of Treatment Effectiveness.

OBJECTIVES: Between 4% and 25% of school-aged children complain of recurrent abdominal pain (RAP) severe enough to interfere with their daily activities. METHODS: We carried out a systematic review of randomised controlled trials (RCTs) in eleven databases and 2 trials registries from inception to June 2016. An update search was run in November 2017. All screening was performed by 2 independent reviewers. Included studies were appraised using the Cochrane risk of bias tool and the evidence assessed using GRADE. We included any dietary, pharmacological or psychosocial intervention for RAP, defined by Apley or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria, in children and adolescents. RESULTS: We included 55 RCTs, involving 3572 children with RAP (21 dietary, 15 pharmacological, 19 psychosocial, and 1 multiarm). We found probiotic diets, cognitive-behavioural therapy (CBT) and hypnotherapy were reported to reduce pain in the short-term and there is some evidence of medium term effectiveness. There was insufficient evidence of effectiveness for all other dietary interventions and psychosocial therapies. There was no robust evidence of effectiveness for pharmacological interventions. CONCLUSIONS: Overall the evidence base for treatment decisions is poor. These data suggest that probiotics, CBT, and hypnotherapy could be considered as part of holistic management of children with RAP. The evidence regarding relative effectiveness of different strains of probiotics is currently insufficient to guide clinical practice. The lack of evidence of effectiveness for any drug suggests that there is little justification for their use outside of well-conducted clinical trials. There is an urgent need for high-quality RCTs to provide evidence to guide management of this common condition.