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.

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.

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.

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.

Neuropathic pain: preclinical and early clinical progress with voltage-gated sodium channel blockers.

Introduction: Neuropathic pain is a chronic condition that significantly affects the quality of life of millions of people globally. Most of the pharmacologic treatments currently in use demonstrate modest efficacy and over half of all patients do not respond to medical management. Hence, there is a need for new, efficacious drugs. Evidence points toward voltage-gated sodium channels as a key target for novel analgesics.Area covered: The role of voltage-gated sodium channels in pain pathophysiology is illuminated and the preclinical and clinical data for new sodium channel blockers and toxin-derived lead compounds are examined. The expansion of approved sodium channel blockers is discussed along with the limitations of current research, trends in drug development, and the potential of personalized medicine.Expert opinion: The transition from preclinical to clinical studies can be difficult because of the inherent inability of animal models to express the complexities of pain states. Pain pathways are notoriously intricate and may be pharmacologically modulated at a variety of targets; it is unlikely that action at a single target could completely abolish a pain response because pain is rarely unifactorial. Combination therapy may be necessary and this could further confound the discovery of novel agents.

Innovative overhead transparent plastic barrier with powered suction technique intended to limit coronavirus disease 2019 aerosols spread during fiber-optic intubation and throughout the surgery.

BACKGROUND: In the context of the current coronavirus pandemic, we propose an inexpensive, innovative overhead transparent plastic barrier with powered suction (OTPBPS) technique using materials that are ubiquitous in the hospital, easy to set up in minutes and well tolerated by the patients. As presented in this case report, it is an effective method to reduce viral spread from patients with positive or suspected yet unconfirmed coronavirus disease 2019 status. CASE DESCRIPTION: A 49-year-old male was admitted to the hospital with a diagnosis of cervical stenosis and a C6-C7 disc herniation with spinal cord compression. The OTPBPS technique was set up to create a negative pressure environment around the patient's head, using a Mayo stand, a transparent plastic bag, and powered wall canister suction. The neurosurgeon successfully performed an anterior cervical discectomy and instrumented fusion under OTPBPS. The patient was satisfied with the intubation and anesthetic management and reported excellent feedback. CONCLUSION: The OTPBPS technique helps control the spread of an aerosolized viral load from the patient's mouth or airway during awake fiber-optic intubation. This technique will help anesthesiologists and other front-line health-care providers manage copious endotracheal secretions and droplet particles, which have an immense infectious potential.

Pharmacological interrogation of TrkA-mediated mechanisms in hippocampal-dependent memory consolidation.

In the brain, the TrkA receptor for Nerve Growth Factor (NGF) is expressed primarily in the cholinergic system. TrkA/NGF support neuronal health and function, and deficiencies in this axis are associated with progressive cholinergic neuron atrophy and death, and with cognitive deficit in disorders such as Down's syndrome and Alzheimer's disease. These observations led to the hypothesis that TrkA agonists may rescue atrophic cholinergic neurons and benefit cognition. Indeed, a small molecule TrkA partial agonist called D3 normalized TrkA signals and improved memory in cognitive impairment models of ageing and an APP mouse model of Alzheimer's disease. Paradoxically, in young healthy mice chronic delivery of D3 caused impaired memory without impairing learning, a form of anterograde amnesia. Here, we use this as a model to study the mechanisms of impaired memory. In young healthy mice acute or chronic treatment with D3 induces hyperactivation of TrkA-mediated signals in hippocampus, and causes a deficit in hippocampal-dependent memory consolidation proximal to drug exposure, without affecting learning or memory retrieval. The impairment after acute drug exposure is reversible. The impairment after long-term drug exposure is irreversible, likely due to a decrease in hippocampal CA1 neuron basal arborization. These findings support the notion of a homeostatic role for TrkA in memory, and demonstrate the differential outcomes of TrkA (hyper)activation in healthy versus disease states.

Vaccination with Tumor-Ganglioside Glycomimetics Activates a Selective Immunity that Affords Cancer Therapy.

Immune targeting of (glyco)protein tumor markers has been useful to develop cancer and virus vaccines. However, the ganglioside family of tumor-associated glycolipids remains intractable to vaccine approaches. Here we show that synthetic antigens mimicking the carbohydrate moiety of GD2 or GD3 gangliosides can be used as vaccines to activate a selective humoral and cellular immunity that is therapeutic against several cancers expressing GD2 or GD3. Adoptive transfer of T cells generated after vaccination elicits tumor-infiltrating lymphocytes of the γδ T cell receptor and CD8+ phenotypes; and affords a high therapeutic index. The glycomimetic vaccine principles can be expanded to target the family of tumor gangliosides and other carbohydrates expressed primarily in pathological states.

Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm.

Neurodegenerative disorders are prevalent, complex and devastating conditions, with very limited treatment options currently available. While they manifest in many forms, there are commonalities that link them together. In this review, we will focus on neurotrophins - a family of related factors involved in neuronal development and maintenance. Neurodegenerative diseases often present with a neurotrophin imbalance, in which there may be decreases in trophic signaling through Trk receptors for example, and/or increases in pro-apoptotic activity through p75. Clinical trials with neurotrophins have continuously failed due to their poor pharmacological properties as well as the unavoidable activation of p75. Thus, there is a need for drugs without such setbacks. Small molecule neurotrophin mimetics are favorable options since they can selectively activate Trks or inactivate p75. In this review, we will initially present a brief outline of how these molecules are synthesized and their mechanisms of action; followed by an update in the current state of neurotrophins and small molecules in major neurodegenerative diseases. Although there has been significant progress in the development of potential therapeutics, more studies are needed to establish clear mechanisms of action and target specificity in order to transition from animal models to the assessment of safety and use in humans.