Circadian pain patterns in human pain conditions - A systematic review.

BACKGROUND: Chronobiology is the science of how physiological processes in the body follow a pattern of time. Pain has been shown to follow a circadian rhythm, with different types of pain having variable expression along this rhythm. OBJECTIVE: This article reviews the nature of diurnal variations in pain along with a discussion of the mechanisms of circadian rhythm of pain. EVIDENCE REVIEW: We conducted a literature search on the PubMed and Google Scholar electronic databases, through April 2022. Publications were screened for English language, full-text availability, and human subjects. Randomized controlled trials and observational trials were included. Data were extracted from studies on patients with acute or chronic pain phenotypes, which provide pain severity data and corresponding diurnal time points. FINDINGS: The literature search led to the inclusion of 39 studies. A circadian pattern of pain was found to be present in nociceptive, neuropathic, central, and mixed pain states. Postoperative pain, fibromyalgia, trigeminal neuralgia, and migraines were associated with higher pain scores in the morning. Temporomandibular joint pain, neuropathic pain, labor pain, biliary colic, and cluster headaches increased throughout the day to reach a peak in the evening or night. Arthritis and cancer pain were not associated with any circadian rhythmicity. Furthermore, the circadian rhythm of pain was not found to be altered in patients on analgesics. CONCLUSION: The results of this review suggest that an understanding of diurnal variation may help improve therapeutic strategies in pain management, for instance through analgesic titration.

Identifying molecular mechanisms of acute to chronic pain transition and potential drug targets.

INTRODUCTION: Chronic pain is pain that lasts more than the normal physiologic healing time at the time of initial insult. The transition from acute to chronic pain has been studied thoroughly. Understanding the mechanisms underlying chronic pain formation is essential for the development of novel treatments and therapeutics for chronic pain prevention. AREA COVERED: The transition from acute to chronic pain has been associated with the intracellular changes caused by repeated stimulus application, or neuronal priming, allowing for the chronicity of pain. Ongoing research studies have shown this priming to occur at various sites along the pathway for the neural transmission of pain. The purpose of this review is to not only elucidate the transition from acute to chronic pain and discuss current studies/trials related to this transition but also to highlight mechanisms involved in the process that could serve as potential targets for chronic pain prevention. EXPERT OPINION: We are providing an overview of novel treatment strategies for preventing the transition from acute to chronic pain. A multifaceted and multimodal approach that invokes multiple targets, at least one from each section (the periphery, the spinal cord, and the brain), would be the best option for tackling this problem.

Dehiscence and Deep Wound Infection After Spinal Cord Stimulator Implant Managed Without Explantation: A Case Report.

Deep infections of spinal cord stimulator devices usually result in explantation, as recommended by some professional societies. However, alternative options should be explored to avoid potential complications that are associated with explantation, and possibly additional procedures required in consideration of reimplantation. In this case, the patient presented with wound dehiscence after implantation. There was suspicion for deep wound infection based on a wound culture that was positive for Staphylococcus aureus, but no purulent material was noted on further inspection. The patient was treated with standard wound-care management and oral antibiotics without removing the device, and recovered while preserving the original system.

Overcoming clinical challenges of refractory neuropathic pain.

INTRODUCTION: Refractory neuropathic pain (ReNP), and its definition, is widely disputed among clinicians due in part to unclear diagnosing guidelines, overall duration of neuropathic pain, and the exhaustiveness of treatment options. Usually, ReNP is defined as chronic, intractable, and unresponsive neuropathic pain that has otherwise been untreatable. AREAS COVERED: In this narrative review, we discuss and summarize the effectiveness of prospective ReNP research conducted over the past 10 years. This research looks at pharmacological and interventional therapies in clinical trial settings. The pharmacological therapies discussed include the use of adjuvant treatments to improve the safety and efficacy of conventional approaches. Different modalities of administration, such as injection therapy and intrathecal drug delivery systems, provide targeted drug delivery. Interventional therapies such as neuromodulation, pulse radiofrequency, and nerve lesioning are more invasive; however, they are increasingly utilized in the field, as reflected in ongoing clinical trials. EXPERT OPINION: Based on the current data from RCTs and systematic reviews, it is clear that single drug therapy cannot be effective and has significant limitations. Transitioning to interventional modalities that showed more promising results sooner rather than later may be even more cost efficient than attempting different conservative treatments with a high failure rate.

Utility of Cervical Sympathetic Block in Treating Post-Traumatic Stress Disorder in Multiple Cohorts: A Retrospective Analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a prevalent and debilitating condition in the United States. Success rates for evidence-based therapies are inconsistent, and many suffer in silence due to the stigmata associated with seeking traditional mental health care. This has led clinicians to explore new therapeutic options, with cervical sympathetic blockade (CSB), performed at the stellate and/or superior cervical ganglion levels, recently emerging as a promising treatment option. Rapid therapeutic onset, improved compliance, and high clinical efficacy rates have made this an attractive approach for both providers and patients. However, to date, CSB as a treatment of PTSD has primarily been used in male patients with military-related trauma. OBJECTIVE: To evaluate the efficacy of CSB as a treatment option for PTSD in both genders and multiple etiologies of psychological trauma. STUDY DESIGN: Retrospective cohort study. SETTING: An established anesthesia pain clinic in Chicago, IL, USA. METHODS: Following retroactive IRB approval, 484 consecutive cases of patients diagnosed with PTSD and treated with CSB, performed by a single provider (December 2016 - February 2020) were analyzed. The primary outcome measurement was the PTSD Checklist Score version DSM IV (PCL-4). Patient demographic and clinical information collected included age, gender, type of trauma leading to PTSD, history of suicidal attempts, and psychiatric medication use. RESULTS: After exclusion of cases due to missing data points, 327 patients were included in the final statistical analysis, having completed both PCL-4 pre and post CSB, between 7- and 30-days post-intervention. The patient population included military men (n = 97), civilian men (n = 85), military women (n = 13) and civilian women (n = 132). We identified 21 types of self-reported trauma leading to PTSD. Average decrease in PCL score for men and women was 28.59 and 29.2, respectively. Statistical analysis of the male population with a military background showed a significantly greater change in corresponding PCL scores than civilians (PCL-M change = -31.83 vs PCL-C change = -24.89). Likewise, women who had a military background had a significantly greater reduction in PCL score than civilians (39.15 vs 28.23). Statistically significant improvements in PTSD symptoms were noted independent of the causative trauma type, gender, age greater than 20, previous suicide attempts, or use of prescription medications for PTSD. Among the 21 types of reported trauma, 19 types reached statistical significance. LIMITATIONS: Limitations include the limited scope of observation giving exclusive focus on pre- and post-PCL data, the limited duration of observation, the self-reported nature of the patient-provided data, and the provision of treatment by a single physician. CONCLUSION: CSB seems to be an effective treatment for PTSD symptoms irrespective of gender, trauma type, PTSD-related drug use, suicide attempt, or age.

No Differences in Pain Scores and Treatment Response in Patients from Different Socioeconomic Areas Within the City of Chicago.

BACKGROUND: It is well established that the experience of chronic pain significantly differs among ethnic-racial groups. There is mixed evidence to suggest that societal influences may contribute to pain prevalence among cultural groups and their treatment response. One possible explanation for differences in pain experience are the differences in socioeconomic status among patients with chronic pain. OBJECTIVE: To determine whether there is any difference in pain scores or treatment responses among patients with different socioeconomic status. STUDY DESIGN: Retrospective analysis. SETTING: Outpatient pain clinic. METHODS: After approval from the Advocate Healthcare Institutional Review Board, we included 1,149 patients treated for different chronic pain conditions who were followed for at least 12 months. Patients were stratified into quartiles determined by median income according to ZIP code. RESULTS: Of the sampled patients, 207 patients lived in ZIP codes with median incomes > $51,294; 515 in ZIP codes with median incomes between $40,083 and $51,294; 332 in ZIP  codes with median incomes between $30,625 and $40,083; and 95 in ZIP codes with median incomes < $30,625. Groups differed in age (P = 0.047), race (P < 0.001), body mass index (BMI) (P = 0.019), utilization of opioid medications (P = 0.011), morphine milligram equivalents (MME) on first visit (P = 0.036), and utilization of membrane stabilizers such as gabapentin (P = 0.019). There were no significant differences among groups in terms of gender (P = 0.531), type of pain experienced (P = 0.679), or time since pain onset (P = 0.174). Groups were treated similarly, with no statistically significant differences in the proportions of patients who had taken various nonopioid medications throughout their treatment course other than membrane stabilizers, the number of patients who received interventional pain management procedures, or MME at last visit. Average pretreatment numeric rating scale pain scores were not significantly different among quartiles (P = 0.079), posttreatment pain scores (P = 0.767), and subjective percent improvement (P = 0.434). LIMITATIONS: This is a single center study and may have limitations in extrapolating to the general population. CONCLUSION: The results of our study show that there are no differences in pain perception or treatment responses in patients from different socioeconomic statuses despite differences among groups in age, BMI, race, utilization of opioid medications, and MME at first visit. Patients at this pain practice appear to have been treated with similar modalities regardless of socioeconomic status.

A novel checklist for anesthesia in neurosurgical cases.

Throughout their training, anesthesiology residents are exposed to a variety of surgical subspecialties, many of which have specific anesthetic considerations. According to the Accreditation Council for Graduate Medical Education requirements, each anesthesiology resident must provide anesthesia for at least twenty intracerebral cases. There are several studies that demonstrate that checklists may reduce deficiencies in pre-induction room setup. We are introducing a novel checklist for neuroanesthesia, which we believe to be helpful for residents during their neuroanesthesiology rotations. Our checklist provides a quick and succinct review of neuroanesthetic challenges prior to case setup by junior residents, covering noteworthy aspects of equipment setup, airway management, induction period, intraoperative concerns, and postoperative considerations. We recommend displaying this checklist on the operating room wall for quick reference.

Low back pain.

Low back pain covers a spectrum of different types of pain (eg, nociceptive, neuropathic and nociplastic, or non-specific) that frequently overlap. The elements comprising the lumbar spine (eg, soft tissue, vertebrae, zygapophyseal and sacroiliac joints, intervertebral discs, and neurovascular structures) are prone to different stressors, and each of these, alone or in combination, can contribute to low back pain. Due to numerous factors related to low back pain, and the low specificity of imaging and diagnostic injections, diagnostic methods for this condition continue to be a subject of controversy. The biopsychosocial model posits low back pain to be a dynamic interaction between social, psychological, and biological factors that can both predispose to and result from injury, and should be considered when devising interdisciplinary treatment plans. Prevention of low back pain is recognised as a pivotal challenge in high-risk populations to help tackle high health-care costs related to therapy and rehabilitation. To a large extent, therapy depends on pain classification, and usually starts with self-care and pharmacotherapy in combination with non-pharmacological methods, such as physical therapies and psychological treatments in appropriate patients. For refractory low back pain, a wide range of non-surgical (eg, epidural steroid injections and spinal cord stimulation for neuropathic pain, and radiofrequency ablation and intra-articular steroid injections for mechanical pain) and surgical (eg, decompression for neuropathic pain, disc replacement, and fusion for mechanical causes) treatment options are available in carefully selected patients. Most treatment options address only single, solitary causes and given the complex nature of low back pain, a multimodal interdisciplinary approach is necessary. Although globally recognised as an important health and socioeconomic challenge with an expected increase in prevalence, low back pain continues to have tremendous potential for improvement in both diagnostic and therapeutic aspects. Future research on low back pain should focus on improving the accuracy and objectivity of diagnostic assessments, and devising treatment algorithms that consider unique biological, psychological, and social factors. High-quality comparative-effectiveness and randomised controlled trials with longer follow-up periods that aim to establish the efficacy and cost-effectiveness of low back pain management are warranted.

Comparative safety review of current treatment options for chronic low back pain and unmet needs: a narrative review.

Introduction: The healthcare expenditures in the United States are substantial for the management of refractory, chronic low back pain (CLBP). The objective of this review is to summarize and evaluate the safety profiles of different pharmacological treatment options used in the management of CLBP.Areas covered: The authors conducted a search of randomized controlled trials (RCTs) assessing the safety profiles of different pharmacological agents used in the management of CLBP. This narrative review covered corticosteroids, opioids, antidepressants, gabapentinoids, nonsteroidal anti-inflammatory drugs, muscle relaxants, anti-nerve growth factor antibodies and topical agents, as monotherapy or in combination.Expert opinion: The risk-benefit ratio of a particular treatment is a subject driving the ongoing development of pharmaceuticals. The most commonly reported AEs across all drug classes are of gastrointestinal nature, followed by neurological and skin-related. These AEs include nausea, dizziness, constipation, arthralgia, headache, dry mouth, pruritus, etc. The majority of the AEs reported are not life-threatening, although they may lower patients' quality of life, thus, affecting their compliance. One of the biggest limitations of our review stems from the paucity of safety assessments in published RCTs. Advances in our understanding of the neurobiology of pain will promote development of new therapeutic strategies.

Herbal Medicine for Pain Management: Efficacy and Drug Interactions.

Complementary and alternative medicines such as herbal medicines are not currently part of the conventional medical system. As the popularity of and global market for herbal medicine grows among all age groups, with supporting scientific data and clinical trials, specific alternative treatments such as herbal medicine can be reclassified as a practice of conventional medicine. One of the most common conditions for which adults use herbal medicine is pain. However, herbal medicines carry safety concerns and may impact the efficacy of conventional therapies. Unfortunately, mechanisms of action are poorly understood, and their use is unregulated and often underreported to medical professionals. This review aims to compile common and available herbal medicines which can be used as an alternative to or in combination with conventional pain management approaches. Efficacy and safety are assessed through clinical studies on pain relief. Ensuing herb-drug interactions such as cytochrome modulation, additive and synergistic effects, and contraindications are discussed. While self-management has been recognized as part of the overall treatment strategy for patients suffering from chronic pain, it is important for practitioners to be able to also optimize and integrate herbal medicine and, if warranted, other complementary and alternative medicines into their care.

Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia.

BACKGROUND: Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate  many hypotheses.The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR. OBJECTIVES: To determine the potential association between FM and IR. SETTING: Subspecialty pain medicine clinics. STUDY DESIGN: Observational cross-sectional study. METHODS: Laboratory data was extracted through a retrospective review of medical records from patients who had met the American College of Rheumatology (ACR) criteria for FM. The Hemoglobin A1c (HbA1c) values from 33 patients with FM were compared with the means of the glycated HbA1c levels of 2 control populations. In addition, established indices of IR [Quantitative Insulin Sensitivity Check Index (QUICKI) and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] were calculated in a subgroup of patients in whom the analytes necessary for these calculations were available. To assess for confounding factors, the associations between HbA1c, QUICKI, HOMA-IR, fasting insulin levels, and glucose, after controlling for age, were explored by multiple analyses of variance with relation to gender and ethnicity. RESULTS: We found an association between IR and FM that was independent of age, gender, and ethnicity. We found that patients with FM belong to a distinct population that can be segregated from the control groups by their HbA1c levels, a surrogate marker of IR. This was demonstrated by analyzing the data after introducing an age correction into a linear regression model. This strategy showed significant differences between patients with FM and control subjects (P < 0.0001 and P  = 0.0002, for 2 separate control populations, respectively). A subgroup analysis using the QUICKI and HOMA-IR showed that all patients with FM in this subgroup (100%) exhibited laboratory abnormalities pointing to IR. LIMITATIONS: Small observational cross-sectional study. There are also intrinsic limitations that are attributed to cross-sectional studies. CONCLUSION: The association demonstrated in this study warrant further investigation, including the pursuit of randomized, double-blind clinical trials to determine the effect of improving insulin sensitivity in FM related pain scores. Such studies could unveil a potential pathogenetic relationship between FM, central pain, and IR. Based on these initial findings, we present the hypothesis that IR may underlie pathological mechanisms leading to central pain. If confirmed, this may lead to a paradigm shift in the management of central pain.

A Retrospective Analysis of Gabapentinoid and Opioids to Opioid Monotherapy for Pain Relief in Patients with Chronic Neck and Low Back Pain.

OBJECTIVE: We compared the reduction in pain and opioid consumption in patients with chronic spinal pain on concomitant gabapentinoids and opioids with patients using opioids only. DESIGN: This was a retrospective chart review of patients with chronic neck or low back pain who were on opioids with at least a 24-month follow-up. SETTING: Single-center pain clinic in an urban setting. SUBJECTS: 167 patients with chronic spinal pain lasting at least six months. METHODS: Patients on gabapentin or pregabalin were included in the gabapentinoid group, while the other patients were included in the non-gabapentinoid group. Primary outcome was assessment of pain scores measured via a numeric rating scale (NRS), and secondary outcomes were response to the treatment (>2 point reduction on NRS) and daily opioid use measured in morphine milliequivalents. RESULTS: Pain scores were reduced in the first six months and plateaued after that in both groups. At the end of 24 months, the average pain score was 6.71 in the gabapentinoid group, while the average pain score was 7.18 in the non-gabapentinoid group. There was no statistical significance between the groups (p = 0.28). There was no difference in response to treatment in gabapentinoid group (33.3%) when compared with non-gabapentinoid group (32.7%). We also failed to find any significant difference in daily opioid usage between the two groups. CONCLUSION: Gabapentinoids may not lead to reduction in pain or opioid consumption in patients with chronic spinal pain. A careful approach must be adopted while prescribing gabapentinoids in the chronic spinal pain patient population.

Methodology for Evidence Synthesis and Development of Comprehensive Evidence-Based Guidelines for Interventional Techniques in Chronic Spinal Pain.

BACKGROUND: The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. OBJECTIVE: To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. METHODS: A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations. RESULTS: Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews. LIMITATIONS: Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques. CONCLUSION: This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and  recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations.

Parasagittal Approach of Epidural Steroid Injection as a Treatment for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Background: Epidural steroid injection (ESI) has proven benefits in controlling chronic low back pain and can be performed via the midline interlaminar (MIL) or transforaminal (TF) approach. A modified interlaminar approach, the parasagittal interlaminar (PIL), has surfaced as a more reliable, safe, and suitable approach to minimize complications related to MIL and TF. Objective: To conduct a systematic review and meta-analysis to assess and compare the effectiveness and safety of PIL with both MIL and TF approaches in adult patients with a history of chronic low back pain. Methods: A literature search was conducted using major electronic databases, such as PubMed, EMBASE, and Cochrane. Selected studies included patients with unilateral radicular symptoms, secondary to lumbar intervertebral disc hernias or degenerative lumbar disc disease, that, additionally, received ESIs via PIL or either MIL or TF under fluoroscopic guidance. Randomized and observational studies with pain relief score and/or functional disability assessment and at least a 2-week follow-up were included. Results: The search led to the initial identification of 174 studies. Following the screening, eight studies were included in the qualitative analysis and seven randomized controlled trials (RCTs) were included in the statistical analysis. PIL showed statistically significantly more pain relief and functional improvement than MIL at 1-, 3-, and 6-month post-procedure. Compared to TF, PIL showed statistically significantly more pain relief at 3- and 6-month after the procedure. Additionally, PIL showed benefits in terms of lower mean fluoroscopy time, less radiation exposure, zero adverse events in all the included studies, no cases of intravascular spread compared with the TF approach, and a higher anterior epidural spread (AES) of PIL compared with TF. Conclusions: Our systematic review and meta-analysis suggest that the PIL approach is an effective and safe alternative to the MIL and TF approaches in patients presenting with chronic low back pain when epidural injections are indicated, demonstrating a higher level of pain relief and a stronger improvement in functionality post-procedure.

Management of CRPS secondary to preganglionic C8 nerve root avulsion: A case report and literature review.

BACKGROUND: Cervical nerve root avulsion is a well-documented result of high-velocity motor vehicle accidents (MVAs). In up to 21% of cases, preganglionic cervical root avulsion can result in a complex regional pain syndrome (CRPS) impacting the quality of life for patients already impaired by motor, sensory, and autonomic dysfunction. The optimal treatment strategies include repeated stellate ganglion blocks (SBGs). CASE DESCRIPTION: A 43-year-old male sustained a high-velocity MVA resulting in the left C8 nerve root avulsion. This resulted in weakness in the C8 distribution, tactile allodynia, and dysesthesias. The magnetic resonance imaging demonstrated an abnormal signal ventral to the C8-T1 level. As the patient was not considered a candidate for surgical intervention secondary to the attendant brachial plexus injury, a C7-C8 epidural steroid injection was performed; this did not provide improvement. Before placing a spinal cord stimulator, the patient underwent a series of six ultrasound-guided SBGs performed 2 weeks apart; there was 75% improvement in pain and strength. Six years later, the patient continues to do well while receiving SBGs 4 times a year. CONCLUSION: A preganglionic cervical nerve root avulsion should not be a contraindication for a stellate ganglion block in a patient with established CRPS.

Physiologically Difficult Airway in the Patient with Severe Hypotension and Metabolic Acidosis.

The expertise to recognize and manage the difficult airway is essential in anesthesiology. Conventionally, this refers to anatomical concerns causing difficulties with facemask ventilation and/or with tracheal intubation. Severe derangements in patients' physiology can make induction and intubation likewise difficult, and approximately 30% of critically ill patients had cardiovascular collapse subsequently to intubation. We present the case of a 58-year-old male with a past medical history of type II diabetes and hypertension who presented with altered mental status due to severe metabolic acidosis with a pH of 6.8 on admission to the intensive care unit. The anesthesia team was called to urgently intubate the patient. Upon arrival, the patient was localizing to pain and was hypocapnic, tachycardic, and hypotensive despite ongoing therapy with norepinephrine, vasopressin, and bicarbonate drips. Bedside point-of-care ultrasound showed hyperdynamic left ventricle with no other abnormalities. The patient was induced with IV ketamine, and dissociation occurred with maintenance of spontaneous respirations, which was followed by laryngoscopy and intubation causing only minimal hemodynamic changes. The patient was subsequently dialyzed and treated supportively. He was discharged from the hospital two weeks later-neurologically intact and at his baseline. Combination of hypotension and severe metabolic acidosis is particularly a challenging setting for airway management and a major risk factor for adverse events, including cardiopulmonary arrest. Hemodynamically stable induction agents should be preferred. In addition, sustaining spontaneous ventilation and avoiding periods of apnea in the peri-intubation period is paramount-any buildup of CO2 could push a critically low pH even lower and cause cardiovascular collapse. Sympathomimetic properties of ketamine make this induction agent a particularly appealing choice in this setting. This case report further supports the concept that severe physiologic perturbations-in which conventional induction techniques are not feasible-should be included in the current definition of a difficult airway.

Can Implementation of Genetics and Pharmacogenomics Improve Treatment of Chronic Low Back Pain?

Etiology of back pain is multifactorial and not completely understood, and for the majority of people who suffer from chronic low back pain (cLBP), the precise cause cannot be determined. We know that back pain is somewhat heritable, chronic pain more so than acute. The aim of this review is to compile the genes identified by numerous genetic association studies of chronic pain conditions, focusing on cLBP specifically. Higher-order neurologic processes involved in pain maintenance and generation may explain genetic contributions and functional predisposition to formation of cLBP that does not involve spine pathology. Several genes have been identified in genetic association studies of cLBP and roughly, these genes could be grouped into several categories, coding for: receptors, enzymes, cytokines and related molecules, and transcription factors. Treatment of cLBP should be multimodal. In this review, we discuss how an individual's genotype could affect their response to therapy, as well as how genetic polymorphisms in CYP450 and other enzymes are crucial for affecting the metabolic profile of drugs used for the treatment of cLBP. Implementation of gene-focused pharmacotherapy has the potential to deliver select, more efficacious drugs and avoid unnecessary, polypharmacy-related adverse events in many painful conditions, including cLBP.

Triaging Interventional Pain Procedures During COVID-19 or Related Elective Surgery Restrictions: Evidence-Informed Guidance from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The COVID-19 pandemic has worsened the pain and suffering of chronic pain patients due to stoppage of "elective" interventional pain management and office visits across the United States. The reopening of America and restarting of interventional techniques and elective surgical procedures has started. Unfortunately, with resurgence in some states, restrictions are once again being imposed. In addition, even during the Phase II and III of reopening, chronic pain patients and interventional pain physicians have faced difficulties because of the priority selection of elective surgical procedures.Chronic pain patients require high intensity care, specifically during a pandemic such as COVID-19. Consequently, it has become necessary to provide guidance for triaging interventional pain procedures, or related elective surgery restrictions during a pandemic. OBJECTIVES: The aim of these guidelines is to provide education and guidance for physicians, healthcare administrators, the public and patients during the COVID-19 pandemic. Our goal is to restore the opportunity to receive appropriate care for our patients who may benefit from interventional techniques. METHODS: The American Society of Interventional Pain Physicians (ASIPP) has created the COVID-19 Task Force in order to provide guidance for triaging interventional pain procedures or related elective surgery restrictions to provide appropriate access to interventional pain management (IPM) procedures in par with other elective surgical procedures. In developing the guidance, trustworthy standards and appropriate disclosures of conflicts of interest were applied with a section of a panel of experts from various regions, specialties, types of practices (private practice, community hospital and academic institutes) and groups. The literature pertaining to all aspects of COVID-19, specifically related to epidemiology, risk factors, complications, morbidity and mortality, and literature related to risk mitigation and stratification was reviewed. The evidence -- informed with the incorporation of the best available research and practice knowledge was utilized, instead of a simplified evidence-based approach. Consequently, these guidelines are considered evidence-informed with the incorporation of the best available research and practice knowledge. RESULTS: The Task Force defined the medical urgency of a case and developed an IPM acuity scale for elective IPM procedures with 3 tiers. These included urgent, emergency, and elective procedures. Examples of urgent and emergency procedures included new onset or exacerbation of complex regional pain syndrome (CRPS), acute trauma or acute exacerbation of degenerative or neurological disease resulting in impaired mobility and inability to perform activities of daily living. Examples include painful rib fractures affecting oxygenation and post-dural puncture headaches limiting the ability to sit upright, stand and walk. In addition, emergency procedures include procedures to treat any severe or debilitating disease that prevents the patient from carrying out activities of daily living. Elective procedures were considered as any condition that is stable and can be safely managed with alternatives. LIMITATIONS: COVID-19 continues to be an ongoing pandemic. When these recommendations were developed, different stages of reopening based on geographical regulations were in process. The pandemic continues to be dynamic creating every changing evidence-based guidance. Consequently, we provided evidence-informed guidance. CONCLUSION: The COVID-19 pandemic has created unprecedented challenges in IPM creating needless suffering for pain patients. Many IPM procedures cannot be indefinitely postponed without adverse consequences. Chronic pain exacerbations are associated with marked functional declines and risks with alternative treatment modalities. They must be treated with the concern that they deserve. Clinicians must assess patients, local healthcare resources, and weigh the risks and benefits of a procedure against the risks of suffering from disabling pain and exposure to the COVID-19 virus.

The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents.

Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.