Acupuncture as Part of Multimodal Analgesia for Chronic Pain.

Background: Chronic pain is a multifactorial condition that is afflicting populations worldwide causing an increasing economic, physical, mental, and emotional burden. Treatments range from medications to interventional procedures to complementary and alternative medicine (CAM), such as acupuncture. This review aims to discuss the use of acupuncture in the treatment of chronic pain, proposed mechanisms, indications, and efficacy for various chronic pain conditions. Results: Evidence is varied on the efficacy and quality of data on the use of acupuncture in the treatment of chronic pain. Recent studies have demonstrated promising results in the support of acupuncture for the use in the treatment of cancer, neck, and back pain, functional dyspepsia, and various chronic abdominal pain syndromes. Conclusion: Acupuncture, deemed well-tolerated and safe to use, has been increasingly studied and is regarded as effective in clinical practice, but its efficacy is limited by the lack of well-conducted, high-quality clinical trials, lower quality evidence, and conflicting study results. Additionally, the exact analgesic mechanism of acupuncture remains to be fully elucidated. Increasing evidence supports the role of acupuncture as therapy in the treatment of cancer, neck, and back pain and functional dyspepsia. Further rigorous studies are needed to fully assess the use of acupuncture in various chronic pain conditions, determine its indications, and optimal treatment schedule. Overall, future studies could benefit from better designed experimental studies, larger groups, and more objectives ways to measure pain reduction and symptom improvement.

Suvorexant in the Treatment of Difficulty Falling and Staying Asleep (Insomnia).

Purpose of Review: Insomnia affects more than 10% of the population and causes significant discomfort and disability. Suvorexant is an orexin receptor antagonist that specifically targets the wake-sleep cycle. This review summarizes recent and seminal evidence in the biological and physiological evidence of insomnia, the mechanism of action of suvorexant in treating insomnia, and clinical evidence regarding its use. Recent Findings: There is no single clear diagnosis for insomnia, and thus prevalence is not entirely clear, but it is estimated to affect 10%-30% of the adult population. Comorbidities include obesity, diabetes, and various psychiatric conditions, and insomnia likely has a contributing role in these conditions. Insomnia, by definition, impacts sleep quality and also wakefulness, including academic success and work efficiency. Insomnia is likely related to genetic susceptibility and a triggering event, leading to hyper-arousal states and functional brain disturbances. This leads to hyperactivity of the hypothalamic-pituitary-adrenal axis, over-secretion of corticotropin-releasing factor, and aberrancy in neurotransmitter release. Though several pharmacological options exist for the treatment of insomnia, there is equivocal data regarding their efficacy or limits to their use due to side effects and contraindications. Suvorexant is a novel dual orexin receptor antagonist, which is shown to improve sleep by reducing arousals. Unlike classical therapeutics, suvorexant does not alter the sleep profile; it prolongs the time spent in each sleep state. Though it may cause some somnolence, it is milder than reported with other drugs. Summary: Multiple clinical studies support the use of suvorexant in insomnia. In primary insomnia, suvorexant is effective (over placebo), as measured by polysomnography and reported by patients, in both attaining and maintaining sleep. Similar, albeit to a smaller degree, results were found in secondary insomnia. Suvorexant carries two significant advantages over existing therapies; it has a much better safety profile in approved doses, and it preserves natural sleep architecture, thus promoting more restful sleep and recovery. Unfortunately, data exists mostly for suvorexant versus placebo, and head-to-head trials with common hypnotics are needed to assess the true efficacy of suvorexant over the alternatives. And while tolerance is less likely to develop, close monitoring of post-marketing data is required to evaluate for long term adverse events and efficacy.

Dorsal Column Stimulation and Cannabinoids in the Treatment of Chronic Nociceptive and Neuropathic Pain: a Review of the Clinical and Pre-clinical Data.

PURPOSE OF REVIEW: The main objective of this review is to appraise the literature on the role of spinal cord stimulation (SCS), cannabinoid therapy, as well as SCS and cannabinoid combination therapy for the management of chronic neuropathic and nociceptive pain. Current research suggests that SCS reduces pain and increases functional status in carefully selected patients with minimal side effects. RECENT FINDINGS: As cannabinoid-based medications become a topic of increasing interest in pain management, data remains limited regarding the clinical efficacy of cannabinoids for pain relief. Furthermore, from a mechanistic perspective, although various pain treatment modalities utilize overlapping pain-signaling pathways, clarifying whether cannabinoids work synergistically with SCS via shared mechanisms remains to be determined. In considering secondary outcomes, the current literature suggests cannabinoids improve quality of life, specifically sleep quality, and that SCS decreases opioid consumption, increases functional capacity, and decreases long-term healthcare costs. These findings, along with the high safety profiles of SCS and cannabinoids overall, incentivize further exploration of cannabinoids as an adjunctive therapy to SCS in the treatment of neuropathic and nociceptive pain.

Monomethyl Fumarate (MMF, Bafiertam) for the Treatment of Relapsing Forms of Multiple Sclerosis (MS).

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies-including antibody therapy and oral agents-were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

Chronic Pain Practices: An Evaluation of Positive and Negative Online Patient Reviews.

BACKGROUND: The role of patient satisfaction continues to play an important role in health care quality measures. The use of online review platforms has been adopted by patients to share their perceptions about the quality of care provided by physicians. Chronic pain practice has unique challenges regarding patient satisfaction. OBJECTIVES: The main goal of this study is to identify the themes associated with positive and negative reviews of chronic pain physicians at publicly available online review platforms. STUDY DESIGN: A retrospective study design. SETTING: We evaluated publicly available online patient-generated reviews of chronic pain physicians from Yelp and Healthgrades. METHODS: This retrospective study evaluated patient-generated reviews of chronic pain physicians from 2 online platforms-Yelp and Healthgrades-between the September 1, 2018 through November 1, 2018. Ninety chronic pain physicians were randomly selected from 4 diverse geographic cities in the United States: New York (NY), Houston (TX), Chicago (IL), and Seattle (WA). Primary outcome was defined as high and low rating scores. Secondary outcome was the proportion of positive and negative attributes (patient, physician, procedure, and administrative attributes) that was associated with high and low rating scores. RESULTS: A total of 1,627 reviews were extracted from 90 physicians evaluated at Yelp and Healthgrades. Of this total review, 1,296 (79.7%) were high scoring and (331) 20.3% were low scoring. Chronic pain providers who were high scoring had positive reviews that consisted of physician attributes (63.5%), administrative attributes (23.4%), and patient attributes (12.2%). The highest proportion of the first 3 physician attributes associated with high ratings were knowledgeable, helpful, and caring. Chronic pain providers who were low scoring had negative reviews that consisted of physician attributes (41.4%), administrative attributes (52.1%), and procedure attributes (5.2%). The highest proportion of the first 3 physician attributes associated with low ratings were disrespectful, unhelpful, and uncaring. LIMITATIONS: First, this study looks at reviews of 4 large cities, thus we may have excluded patient populations with substantially different preferences as health care consumers. Second, it is impossible to confirm the validity of individual reviewers' interactions with the pain management specialist who provided care or validate the identity of the reviewers. Third, it is very difficult, or even impossible, to tell if the rater is a patient or someone posing as a patient, such as an unhappy employee or a business competitor. CONCLUSIONS: Online platforms provide a medium that facilitates immediate communication among patients. These platforms may provide timely data for chronic pain physicians to gain more insight into the quality of care perceived by patients, thereby aiding providers to improve on ways to optimize patient-care experiences and encounters. KEY WORDS: Chronic pain practice, online review, patient review, patient satisfaction.

Cellular Analysis of Silencing the Huntington's Disease Gene Using AAV9 Mediated Delivery of Artificial Micro RNA into the Striatum of Q140/Q140 Mice.

BACKGROUND: The genetic mutation in Huntington's disease (HD) is a CAG repeat expansion in the coding region of the huntingtin (Htt) gene. RNAi strategies have proven effective in substantially down-regulating Htt mRNA in the striatum through delivery of siRNAs or viral vectors based on whole tissue assays, but the extent of htt mRNA lowering in individual neurons is unknown. OBJECTIVE: Here we characterize the effect of an AAV9-GFP-miRHtt vector on Htt mRNA levels in striatal neurons of Q140/Q140 knock-in mice. METHODS: HD mice received bilateral striatal injections of AAV9-GFP-miRHtt or AAV9-GFP at 6 or 12 weeks and striata were evaluated at 6 months of age for levels of Htt mRNA and protein and for mRNA signal within striatal neurons using RNAscope multiplex fluorescence in situ hybridization. RESULTS: Compared to controls, the striatum of 6-month old mice treated at 6 or 12 weeks of age with AAV9-GFP-miRHtt showed a reduction of 40-50% in Htt mRNA and lowering of 25-40% in protein levels. The number of Htt mRNA foci in medium spiny neurons (MSNs) of untreated Q140/Q140 mice varied widely per cell (0 to 34 per cell), with ∼10% of MSNs devoid of foci. AAV9-GFP-miRHtt treatment shifted the distribution toward lower numbers and the percentage of cells without foci increased to 14-20%. The average number of Htt mRNA foci per MSN was reduced by 43%. CONCLUSIONS: The findings here show that intrastriatal infusion of an AAV9-GFP-miRHtt vector lowers mRNA expression of Htt in striatum by ∼50%, through a partial reduction in the number of copies of mutant Htt mRNAs per cell. These findings demonstrate at the neuronal level the variable levels of Htt mRNA expression in MSNs and the neuronal heterogeneity of RNAi dependent Htt mRNA knockdown.

Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain.

Applications of RNA interference for neuroscience research have been limited by a lack of simple and efficient methods to deliver oligonucleotides to primary neurons in culture and to the brain. Here, we show that primary neurons rapidly internalize hydrophobically modified siRNAs (hsiRNAs) added directly to the culture medium without lipid formulation. We identify functional hsiRNAs targeting the mRNA of huntingtin, the mutation of which is responsible for Huntington's disease, and show that direct uptake in neurons induces potent and specific silencing in vitro. Moreover, a single injection of unformulated hsiRNA into mouse brain silences Htt mRNA with minimal neuronal toxicity. Thus, hsiRNAs embody a class of therapeutic oligonucleotides that enable simple and straightforward functional studies of genes involved in neuronal biology and neurodegenerative disorders in a native biological context.