Gut Microbiome in Anesthesiology and Pain Medicine.

The gut microbiome plays critical roles in human health and disease. Recent studies suggest it may also be associated with chronic pain and postoperative pain outcomes. In animal models, the composition of the gut microbiome changes after general anesthesia and affects the host response to medications, including anesthetics and opioids. In humans, the gut microbiome is associated with the development of postoperative pain and neurocognitive disorders. Additionally, the composition of the gut microbiome has been associated with pain conditions including visceral pain, nociplastic pain, complex regional pain syndrome, and headaches, partly through altered concentration of circulating bacterial-derived metabolites. Furthermore, animal studies demonstrate the critical role of the gut microbiome in neuropathic pain via immunomodulatory mechanisms. This article reviews basic concepts of the human gut microbiome and its interactions with the host and provide a comprehensive overview of the evidence linking the gut microbiome to anesthesiology, critical care, and pain medicine.

Gut microbiome: pertinence in fibromyalgia.

The human gut microbiome constitutes a diverse and dynamic community of microorganisms that inhabit the digestive tract. In recent years, there is growing appreciation for the role of the gut microbiome in host health and disease. Gut bacteria are involved in the pathogenesis of numerous medical conditions in a variety of medical fields including gastroenterology, metabolic, rheumatologic, neurologic and psychiatric disorders. Recently, evidence is mounting that gut bacteria could also play a role in chronic pain and specifically fibromyalgia (FM). The composition of the gut bacterial community is altered in individuals with FM, with an altered abundance of a small subset of bacterial species. Some of these species, either with increased or decreased abundance in patients, have established metabolic activity which could have pertinence in the expression of FM symptoms. The putative mechanisms which could allow these bacterial species to affect pain, fatigue, mood and other symptoms include the entry of short-chain-fatty-acids, bile acids, neurotransmitters and bacterial antigens into the host circulation. While these are merely the first steps in understanding the role of the gut microbiome in chronic pain and specifically FM, one might envision exciting future perspectives for better mechanistic understanding of FM, for the development of objective diagnostic aids and potentially for new therapeutic modalities.

Specialized Pain Clinics in Primary Care: Common Diagnoses, Referral Patterns and Clinical Outcomes - Novel Pain Management Model.

An estimated 19% of the adult population in western countries lives with chronic pain. Pain management lies mainly within the primary care and community setting. We evaluated the outcome of a new model of secondary care clinics, conducted by primary care physicians with specialized training in pain medicine. Data on referral patterns, prevalence of pain diagnosis, and medication consumption were recorded at five secondary pain management clinics in the community setting. In total, 997 patients with pain attended 2,652 visits (average 2.7 visits per patient) during 12 mo. Patients' age ranged from 18 to 92 yr (mean 59 ± 19). Mean pain intensity on the first visit, evaluated by the visual analogue scale was 7.7/10. Myofascial pain syndrome was the most common diagnosis (82%). Treatment included dry needling or trigger point injection (82%), manual myofascial release (23%), and pharmacotherapy (38%). Significant short-term improvement after treatment was reported by 75% of patients, and 72% reported long-term improvement. Four percent were referred to tertiary care pain clinics, 5% were referred to other specialists, and 5% to imaging. Secondary, community-based pain clinics, run by specially-trained primary physicians, demonstrated feasibility. The vast majority of patients referred to the clinics were treated using simple, inexpensive modalities, while sparing referrals to unnecessary consultation visits, imaging tests, and medications.

Position Statement of the Israeli Society for Musculoskeletal Medicine on Intramuscular Stimulation for Myofascial Pain Syndrome-A Delphi Process.

OBJECTIVE: To develop consensus on a position paper on the use of intramuscular stimulation (IMS) for the treatment of myofascial pain syndrome (MPS) by physicians in Israel. METHODS: The Israeli Society of Musculoskeletal Medicine ran a modified Delphi process to gather opinions from a multidisciplinary expert panel. Eight experts in the treatment of MPS were chosen and asked to participate, and six participated. The position paper was iterated three times. RESULTS: After three iterations, general consensus was reached by all six experts. The general statement that was agreed on was: "IMS is one of the preferred treatments for myofascial pain syndrome. The treatment is evidence-based, effective, safe, and inexpensive. The position of the Israeli Society of Musculoskeletal Medicine is that the treatment should be taught and used by all primary care physicians and those physicians in other areas of medicine who deal with pain in their work." CONCLUSIONS: The position paper is a basis for clinical work and education programs for physicians interested in a better understanding and ability to treat patients with a musculoskeletal complaint or manifestation of disease.

Synaptic size dynamics as an effectively stochastic process.

Long-term, repeated measurements of individual synaptic properties have revealed that synapses can undergo significant directed and spontaneous changes over time scales of minutes to weeks. These changes are presumably driven by a large number of activity-dependent and independent molecular processes, yet how these processes integrate to determine the totality of synaptic size remains unknown. Here we propose, as an alternative to detailed, mechanistic descriptions, a statistical approach to synaptic size dynamics. The basic premise of this approach is that the integrated outcome of the myriad of processes that drive synaptic size dynamics are effectively described as a combination of multiplicative and additive processes, both of which are stochastic and taken from distributions parametrically affected by physiological signals. We show that this seemingly simple model, known in probability theory as the Kesten process, can generate rich dynamics which are qualitatively similar to the dynamics of individual glutamatergic synapses recorded in long-term time-lapse experiments in ex-vivo cortical networks. Moreover, we show that this stochastic model, which is insensitive to many of its underlying details, quantitatively captures the distributions of synaptic sizes measured in these experiments, the long-term stability of such distributions and their scaling in response to pharmacological manipulations. Finally, we show that the average kinetics of new postsynaptic density formation measured in such experiments is also faithfully captured by the same model. The model thus provides a useful framework for characterizing synapse size dynamics at steady state, during initial formation of such steady states, and during their convergence to new steady states following perturbations. These findings show the strength of a simple low dimensional statistical model to quantitatively describe synapse size dynamics as the integrated result of many underlying complex processes.

Comparison of Vestibular/Ocular Motor Screening (VOMS) and Computerized Eye-tracking to Identify Exposure to Repetitive Head Impacts.

INTRODUCTION: Military service members (SMs) are exposed to repetitive head impacts (RHIs) in combat and training that are purported to adversely affect brain health, including cognition, behavior, and function. Researchers have reported that RHI from blast-related exposure may affect both vestibular and ocular function, which in turn may be related to symptomology. As such, an examination of the effects of RHI on exposed military SMs should incorporate these domains. To date, researchers have not compared groups of exposed special operations forces (SOF) operators on combined clinical vestibular/ocular and eye-tracker-based outcomes. Therefore, the primary purpose of this study was to compare participant-reported symptoms and performance on the Vestibular/Ocular Motor Screening (VOMS) tool with performance on the computerized RightEye tracking system between SOF operators exposed to blast-related RHI and healthy controls without blast-related exposure. In addition, the study aimed to compare subgroups of snipers and breachers exposed to RHI to controls on the preceding metrics, as well as identify a subset of individual (demographic) factors, participant-reported symptoms, and performance metrics on VOMS and RightEye that best identify SOF operators exposed to RHI from unexposed controls. MATERIALS AND METHODS: The study involved a cross-sectional design including 25 Canadian SOF SMs comprised of breachers (n = 9), snipers (n = 9), and healthy, unexposed controls (n = 7). The former 2 groups were combined into an RHI group (n = 18) and compared to controls (n = 7). Participants provided demographics and completed a self-reported concussion-related symptom report via the Military Acute Concussion Evaluation 2, the VOMS, and RightEye computerized eye-tracking assessments. Independent samples t-tests and ANOVAs were used to compare the groups on the outcomes, with receiver operating characteristic curve and area under the curve (AUC) analyses to identify predictors of blast exposure. This study was approved by the Defence Research Development Canada Human Research Ethics Committee and the Canadian Forces Surgeon General/Special Forces Command. RESULTS: The results from t-tests supported group differences for age (P = .012), participant-reported symptoms (P = .006), and all VOMS items (P range = <.001-.02), with the RHI group being higher than healthy controls on all variables. ANOVA results supported group differences among snipers, breachers, and controls for age (P = .01), RightEye saccades (P = .04), participant-reported total symptom severity (P = .03), and VOMS total scores (P = .003). The results of the receiver operating characteristic curve analyses supported age (AUC = 0.81), Military Acute Concussion Evaluation 2 participant-reported total symptom severity (AUC = 0.87), and VOMS total scores (AUC = 0.92) as significant predictors of prior blast exposure. CONCLUSIONS: Participant-reported concussion symptoms, VOMS scores, and age were useful in identifying SOF operators exposed to RHI from controls. RightEye metrics were not useful in differentiating RHI groups from controls. Differences between snipers and breachers warrant further research. Overall, the findings suggest that VOMS may be a useful tool for screening for the effects of exposure to RHI in SOF operators. Future investigations should be conducted on a larger sample of military SMs, consider additional factors (e.g., RHI exposure levels, medical history, and sex), and include additional assessment domains (e.g., balance, cognitive, and psychological).

Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity.

ABSTRACT: Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.

Long-term relationships between synaptic tenacity, synaptic remodeling, and network activity.

Synaptic plasticity is widely believed to constitute a key mechanism for modifying functional properties of neuronal networks. This belief implicitly implies, however, that synapses, when not driven to change their characteristics by physiologically relevant stimuli, will maintain these characteristics over time. How tenacious are synapses over behaviorally relevant time scales? To begin to address this question, we developed a system for continuously imaging the structural dynamics of individual synapses over many days, while recording network activity in the same preparations. We found that in spontaneously active networks, distributions of synaptic sizes were generally stable over days. Following individual synapses revealed, however, that the apparently static distributions were actually steady states of synapses exhibiting continual and extensive remodeling. In active networks, large synapses tended to grow smaller, whereas small synapses tended to grow larger, mainly during periods of particularly synchronous activity. Suppression of network activity only mildly affected the magnitude of synaptic remodeling, but dependence on synaptic size was lost, leading to the broadening of synaptic size distributions and increases in mean synaptic size. From the perspective of individual neurons, activity drove changes in the relative sizes of their excitatory inputs, but such changes continued, albeit at lower rates, even when network activity was blocked. Our findings show that activity strongly drives synaptic remodeling, but they also show that significant remodeling occurs spontaneously. Whereas such spontaneous remodeling provides an explanation for "synaptic homeostasis" like processes, it also raises significant questions concerning the reliability of individual synapses as sites for persistently modifying network function.

Differential Sensitization of Muscle versus Fascia in Individuals with Low Back Pain.

Muscles and the deep fascia surrounding them have been suggested to play an important role in various musculoskeletal pain conditions including low back pain. Both have been shown to host rich nociceptive innervation and to undergo changes in individuals with chronic pain. However, evidence for the respective contribution of muscle and fascia sensitization in humans with myofascial pain syndrome is lacking. Here, we studied the sensitization of muscle and fascia in individuals with myofascial low back pain. Twenty individuals with acute (5) and chronic (15) myofascial low back pain of the quadratus lumborum muscle and a matched control group of twenty healthy individuals were recruited and clinically evaluated. All participants underwent ultrasound-guided needling of their subcutaneous tissue, deep fascia and quadratus lumborum muscle. Reported pain intensity and episodes of muscle twitching were recorded and analyzed. Among pain patients, both muscles and deep fascia demonstrated pain hypersensitivity, but muscles were significantly more sensitized than the deep fascia. No difference between acute- or chronic-pain patients was observed. Results of this study suggest that while both deep fascia and muscle show pain sensitization in both early and chronic stages of low back pain, muscles are more sensitized than fascia.

Dietary Intake Is Unlikely to Explain Symptom Severity and Syndrome-Specific Microbiome Alterations in a Cohort of Women with Fibromyalgia.

BACKGROUND: Significant alterations were recently identified in the composition and putative function of the gut microbiome in women with fibromyalgia. As diet can influence the composition of the gut microbiome, differences in nutritional intake could, in theory, account for some of these specific fibromyalgia microbiome alterations. The current study aims to compare the diet of women with fibromyalgia to that of controls in order to explore possible associations between the intake of certain nutrients, symptom severity and gut microbiome composition. METHODS: The study population was comprised of 56 women with fibromyalgia and 68 controls. Dietary intake was assessed using the NIH Automated Self-Administered 24 h recall, following dietitian's instructions and the completion of a three-day dietary recall. The gut microbiome was assessed by 16S ribosomal RNA gene sequencing of stool samples. RESULTS: Most demographic and anthropometric characteristics were comparable between groups. The average energy and macronutrient intake (total and relative) and overall diet quality score were not different between patients and controls, nor were the main vitamins, minerals, fatty acids, alcohol, caffeine, sugar or fiber intakes. The daily intake of micronutrients and normalized macronutrients in women with fibromyalgia was largely not correlated with disease-specific measures, including pain intensity, fatigue, cognitive symptoms and quality of sleep, or with the relative quantity of almost any of the gut microbiome bacterial taxa differentially abundant in fibromyalgia. CONCLUSION: These data demonstrate that dietary intakes, as evaluated by self-reported questionnaires, probably cannot explain the syndrome-specific differences in gut microbiome or the clinical phenotype of fibromyalgia.

[The approach to the treatment of lower-limb varicose veins].

Varicose veins have been described as early as the classical period of ancient Greece, and continue to affect the quality of life of up to one third of the population in the industrialized world. In recent years considerable progress has been achieved in understanding the pathological basis of this condition and in the development of new treatment modalities. The treatment of varicose veins of the lower limbs is primarily aimed at alleviating the symptoms, which include pain, pruritus, heaviness, ulceration, hemorrhage, and at improving unaesthetic appearance, but has also been shown to significantly improve measurable parameters of patients' quality of life and functional scales. This work reviews the current evidence on the four major treatment methods at hand: 1. Compression; 2. Stripping surgery; 3. Ultrasound guided foam sclerotherapy; 4. Thermal ablation by laser, radiofrequency or steam. Compression is a simple, low-cost treatment, but has low rates of patient compliance. The remaining invasive interventions are equally efficacious but differ considerably in their demand of skilled personnel and equipment, their adverse effects, the length of expected recovery and their economic costs. The new endovenous interventions can be performed in an ambulatory clinic under local anesthesia. They are at least as efficacious as surgery in short- and medium-term follow-up, but evidence on their long-term efficacy is still Lacking.

Fibromyalgia in Older Individuals.

Fibromyalgia (FM) is a condition of chronic widespread pain (CWP) that can occur throughout the life cycle and is likely underrecognized in older patients. FM is associated with considerable suffering and reduction in quality of life and may occur as a unique condition, but in older patients is most likely to be associated with another medical illness. Understood mechanistically to be a sensitization of the nervous system, recently identified as nociplastic pain, FM is accepted as a valid medical illness that requires a positive diagnosis and directed treatments. The cornerstone of treatments for FM are nonpharmacologic interventions, with the understanding that medications provide only modest benefit for most patients, and with particular concern about adverse effects in older patients. If FM is not recognized, treatments may be misdirected to the other medical condition, with failure to address FM symptoms, leading to overall poor outcome. In contrast, new complaints in older patients should not immediately be attributed to FM, and physicians should be vigilant to ensure that onset of a new illness is not ignored. As FM is most often a lifelong condition, patients should be encouraged to identify their own personal strategies that can attenuate symptoms, especially when symptoms flare. Continued life participation should be the outcome goal.

Effects of a patient-tailored integrative oncology intervention in the relief of pain in palliative and supportive cancer care.

CONTEXT AND OBJECTIVES: The present study examined the impact of an integrative oncology treatment program in the relief of pain in patients undergoing chemotherapy and/or palliative care. METHODS: In this pragmatic prospective controlled study, patients undergoing chemotherapy and/or palliative care were referred by their oncology healthcare providers to an integrative physician (IP) consultation, followed by weekly integrative treatments. Patients attending ≥ 4 sessions during the first 6 weeks of the study were considered to be highly adherent to integrative care (AIC). Pain was assessed at baseline and at 6 and 12 weeks using the ESAS (Edmonton Symptom Assessment Scale) and EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) tools. RESULTS: Of 815 eligible patients, 484 (59.4%) were high-AIC and 331 low-AIC. Mean pain scores decreased significantly from baseline to 6 and 12 weeks in both groups. However, ESAS and EORTC pain scores improved significantly more in the high-AIC group at 6 weeks (p= 0.008), though not at 12 weeks. Between-group analysis of participants undergoing adjuvant/neo-adjuvant chemotherapy showed higher pain reduction in the high-AIC group at 6 weeks (ESAS, p = 0.006; EORTC, p = 0.046), as was the case with patients receiving palliative care (ESAS p = 0.04; EORTC p = 0.056). CONCLUSIONS: High adherence to integrative care was found to be associated with a greater effect on pain relief at 6 weeks but not at 12 weeks in patients undergoing chemotherapy and/or palliative care.

The Case for Comorbid Myofascial Pain-A Qualitative Review.

Myofascial pain syndrome is widely considered to be among the most prevalent pain conditions, both in the community and in specialized pain clinics. While myofascial pain often arises in otherwise healthy individuals, evidence is mounting that its prevalence may be even higher in individuals with various comorbidities. Comorbid myofascial pain has been observed in a wide variety of medical conditions, including malignant tumors, osteoarthritis, neurological conditions, and mental health conditions. Here, we review the evidence of comorbid myofascial pain and discuss the diagnostic and therapeutic implications of its recognition.

Cannabis and Pain Treatment-A Review of the Clinical Utility and a Practical Approach in Light of Uncertainty.

Over the past decade the phenomenon of cannabis as a legitimate form of treatment for pain has overwhelmed the medical community, especially in the field of pain. From a status of a schedule 1 substance having no currently accepted medical use and being considered to have high potential for abuse, its use has mushroomed to over 50,000 legal medical users per year in Israel alone. There appear to be many reasons behind this phenomenon-medical, sociological, and economical. Thus, what is cannabis? An abusive substance or a medication? Should it be incorporated into current biomedical practice, and how should it be administered? Finally, what is the evidence for the beneficial and detrimental effects of cannabis? This article reviews and discusses the current literature regarding the beneficial and the detrimental effects of medical cannabis in the treatment of pain. We further discuss the problems and challenges facing the medical community in this domain and offer a practical approach to deal with these challenges.

Comparing the Efficiency of Software-Based Speech Recognition Versus Traditional Telephone Transcription in an Outpatient Physical Medicine and Rehabilitation Practice.

INTRODUCTION: Speech recognition (SR) uses computerized word recognition software that automatically transcribes spoken words to written text. Some studies indicate that SR may improve efficiency of electronic charting as well as associated cost and turnaround time1,2, but it remains unclear in the literature whether SR is superior to traditional transcription (TT). This study compared the impact of report generation efficiency of SR to TT at the Canadian Armed Forces Health Services Centre. MATERIALS AND METHODS: Dragon Medical Dictation™ SR software and traditional telephone dictation TT were used for two prespecified clinical days per week. In order to adjust for note length, total transcription efficacy was calculated as follows: word count/[dictation time + correction time]. The means and standard deviations were then separately calculated for TT visits and for SR visits. Differences in transcription efficacy and in visit measures, including patient demographics, visit duration, number of issues raised during the visit, and interventions performed, were compared using ANOVA, with the significance level set to 0.05. RESULTS: A total of 340 consecutive visits were analyzed; 198 were dictated over the phone using TT and 142 were transcribed using SR software. Dictation efficacy was significantly higher (p < 0.0001) for TT as compared to SR, while turnaround times were shorter for SR (0.12 versus 4.75 days). CONCLUSIONS: In light of these results, the Canadian Forces Health Services Centre in Ottawa has returned to use of TT because the relative inefficiency of report generation was deemed to have a greater impact on clinical care when compared to slower dictation turnaround time.

Interventional Pain Management for Cancer Pain: An Analysis of Outcomes and Predictors of Clinical Response.

BACKGROUND: Interventional procedures are offered routinely to patients seen in McGill University's interdisciplinary cancer pain management program. However, publications on these procedures are scarce, making it difficult to predict which patients may benefit from them. OBJECTIVES: We hypothesized that interventional pain procedures offered to cancer patients could provide relief of pain as well as other symptoms. Furthermore, some variables may predict the efficacy of such procedures. STUDY DESIGN: We conducted a retrospective chart review of interventional pain management procedures. SETTING: The procedures reviewed were conducted at the Cancer Pain Program and performed at the interventional suites of the McGill University Health Centre. METHODS: The retrospective chart review included interventional pain management procedures performed between June 2015 and March 2017. Demographic data, details about the underlying cancer and about the procedure and peripTrocedural patients' reported outcomes were recorded for analysis. RESULTS: Eighty-two of 126 procedures were included for analysis. Most patients presented with metastatic disease (75%). Eighty percent of the patients reported pain relief, with the average pain severity decreasing by more than 2 points on a 0-to-10 Numeric Rating Scale for pain (from 6.5 of 10 to 4.2 of 10). Forty-three percent of patients were considered responders (>= 50% pain relief). Responders also reported a significant decrease in fatigue, depression, anxiety, drowsiness, and improved well-being. Among responders, average daily opioid use decreased significantly, by 60% on average. None of the analyzed variables correlated with the response; however, psychosocial variables like anxiety and depression showed a nonsignificant trend towards predicting procedure failure. LIMITATIONS: The core limitations of this study are its size and retrospective nature. CONCLUSIONS: In this cohort of cancer pain patients, interventional cancer pain procedures provided effective pain relief and other benefits, including pain relief, reduced burden of symptoms, and reduction of opioid intake, while demonstrating a favorable safety profile. Patients with poorer ratings of depression and fatigue derived less benefit from procedures, suggesting that offering such procedures as part of patients' treatment plan would be sensible, rather than leaving interventions for later stages.

Medical Cannabis for Older Patients.

Interest in the medicinal use of cannabis and cannabinoids is mounting worldwide. Fueled by enthusiastic media coverage, patients perceive cannabinoids as a natural remedy for many symptoms. Cannabinoid use is of particular interest for older individuals who may experience symptoms such as chronic pain, sleep disturbance, cancer-related symptoms and mood disorders, all of which are often poorly controlled by current drug treatments that may also incur medication-induced side effects. This review provides a summary of the evidence for use of cannabinoids, and medical cannabis in particular, for this age group, with attention to efficacy and harms. Evidence of efficacy for relief of an array of symptoms is overall scanty, and almost all study participants are aged < 60 years. The risk of known and potential adverse effects is considerable, with concerns for cognitive, cardiovascular and gait and stability effects in older adults. Finally, in light of the paucity of clinical evidence and increasing patient requests for information or use, we propose a pragmatic clinical approach to a rational dialogue with older patients, highlighting the importance of individual benefit-risk assessment and shared patient-clinician decision making.