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ABSTRACTIntroductionLX-9211 is a drug designed to treat neuropathic pain conditions. It functions by inhibiting the adaptor-associated kinase 1 (AAK1) enzyme which promotes clathrin-dependent endocytosis. Preclinical studies have shown that LX-9211 does produce a reduction in nociceptive related behaviors and produces no major adverse effects in rats. Thus, LX-9211 has advanced to clinical trials to assess its safety and efficacy in humans. So far, phase 1 and phase 2 clinical trials involving patients with postherpetic neuralgia and diabetic peripheral neuropathic pain have been conducted with phase 3 trials planned in the future.Areas coveredThis paper highlights preclinical studies involving LX-9211 in rodents. Additionally, phase 1 clinical trials examining the safety of LX-9211 in healthy subjects as well as phase 2 studies looking at the safety and efficacy of LX-9211 compared to placebo in patients with diabetic peripheral neuropathic pain and postherpetic neuralgia are also discussed.Expert opinionIn phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety.

ABSTRACTIntroductionNeuropathic pain (NP) conditions involve lesions to the somatosensory nervous system leading to chronic and debilitating pain. Many patients suffering from NP utilize pharmacological treatments with various drugs that seek to reduce pathologic neuronal states. However, many of these drugs show poor efficacy as well as cause significant adverse effects. Because of this, there is a major need for the development of safer and more efficacious drugs to treat NP.Areas coveredIn this review, we analyzed current treatments being developed for a variety of NP conditions. Specifically, we sought drugs in phase II/III clinical trials with indications for NP conditions. Various databases were searched including Google Scholar, PubMed, and clinicaltrials.gov.Expert opinionAll the mentioned targets for treatments of NP seem to be promising alternatives for existing treatments that often possess poor side effect profiles for patients. However, gene therapy potentially offers the unique ability to inject a plasmid containing growth factors leading to nerve growth and repair. Because of this, gene therapy appears to be the most intriguing new treatment for NP.

Chronic nonmalignant pain is recognized as a complex, dynamic, phenomenological interplay between biological, psychological, and social factors that are individual to the person suffering from it. Therefore, its management and treatment ought to entail the individual’s biopsychosocial aspects that are often addressed by collaborative, inter/multidisciplinary multimodal care, as there is no biologic treatment. In an effort to enhance inter/multidisciplinary multimodal care, a narrative review of arts therapy as a mind–body intervention and its efficacy in chronic pain populations has been conducted. Changes in emotional and physical symptoms, especially pain intensity, during arts therapy sessions have also been discussed in in the context of attention distraction strategy. Arts therapy (visual art, music, dance/movement therapy, etc.) have been investigated to summarize relevant findings and to highlight further potential benefits, limitations, and future directions in this area. We reviewed 16 studies of different design, and the majority reported beneficial effects of art therapy in patients’ management of chronic pain and improvement in pain, mood, stress, and quality of life. However, the results are inconsistent and unclear. It was discovered that there is a limited amount of high-quality research available on the implications of arts therapy in chronic nonmalignant pain management. Due to the reported limitations, low effectiveness, and inconclusive findings of arts therapy in the studies conducted so far, further research with improved methodological standards is required.

Introduction: Despite the growing evidence for the anticancer effect of metformin or its combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the efficacies and side effects of such strategies in non-small cell lung cancer (NSCLC) patients with or without type 2 diabetes mellitus (T2DM) are not well understood. This meta-analysis was performed to determine the efficacy and side effects of metformin combined with EGFR-TKIs (MET-EGFR-TKIs) for the treatment of NSCLC with or without T2DM. Methods: PubMed and Cochrane Library databases were used to retrieve relevant studies through August 2020 using the keywords “metformin”, “EGFR-TKIs” (“gefitinib” or “erlotinib” or “afatinib” or “icotinib” or “dacomitinib”) and “lung cancer”. The patients in the experimental group received MET-EGFR-TKIs, while those in the control group received only EGFR-TKIs. The outcome analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Random-effect models and fixed-effect models were used to estimate the combined hazard ratio (HR) and odds ratio (OR) depending on the data heterogeneity. Three studies (including 1996 patients) were included in the current meta-analysis. Results: There were significant differences in PFS (HR 0.84; 95% confidence interval (CI) 0.75–0.95; P= 0.004) and OS (HR 0.77; 95% CI, 0.50–1.04; P< 0.001) between the MET-EGFR-TKI and EGFR-TKI groups. Although the ORR (OR 1.38; 95% CI 0.66–2.88; P= 0.105) and DCR (OR 2.61, 95% CI 0.68–9.95, P= 0.160) were improved, there was no statistical significance. OS subgroup analysis showed that the combination was more effective in NSCLC with T2DM than in NSCLC without T2DM (HR 0.84; 95% CI 0.74–0.95; P< 0.005). Conclusions: MET-EGFR-TKIs provided benefits for PFS and OS, and OS subgroup analysis showed that patients with NSCLC with T2DM received greater benefit than NSCLC patients without T2DM. However, further large-scale, well-designed randomized controlled trials (RCTs) are warranted to confirm the findings in the present investigation.

Introduction: In recent years, the erector spinae plane block (ESPB) has seen widespread use to treat acute and chronic pain in the regions of the thoracic spine. While limited data suggest its increasing utilization for pain management distal to the thoracic, abdomen and trunk, the anesthetic spread and analgesic mechanism of ESPB at the level of the lumbar spine has not been fully described or understood. Methods: This is an observational anatomic cadaveric study to assess the distribution of solution following an ESPB block performed at the fourth lumbar vertebrae (L4) using ultrasound guidance to evaluate the spread of a 20 ml solution consisting of local anesthetic and methylene blue. The study was performed in an anatomy lab in a large academic medical center. Following injection of local anesthetic with contrast dye, cadaveric dissection was performed to better understand the extent of contrast dye and to determine the degree of staining to further predict analgesic potential. We reviewed the findings of other ESPB cadaveric studies currently available for comparison. Results: Following cadaveric dissection in an anatomy lab, the contrast dye was observed in the ESP space, and staining was found most cranially at L2 and extending caudally underneath the sacrum. Evaluating the depth of its spread, we found it to be confined to the posterior compartment of the spine sparing the nerve roots bilaterally, which is consistent with the only other cadaveric study of ESPB performed at L4. Conclusion: Our results demonstrate the clinical utility of lumbar ESPB where posterior confinement of local anesthesia is preferred. However, further investigation is needed to determine the efficacy of ESPB in lower extremity analgesia which is predicated on ventral nerve root involvement.

Chronic pain is a common source of morbidity in many patient populations worldwide. There are growing concerns about the potential side effects of currently prescribed medications and a continued need for effective treatment. Related to these concerns, peripheral nerve stimulation has been regaining popularity as a potential treatment modality. Peripheral nerve stimulation components include helically coiled electrical leads, which direct an applied current to afferent neurons providing sensory innervation to the painful area. In theory, the applied current to the peripheral nerve will alter the large-diameter myelinated afferent nerve fibers, which interfere with the central processing of pain signals through small-diameter afferent fibers at the level of the spinal cord. Multiple studies have shown success in the use of peripheral nerve stimulation for acute post-surgical pain for orthopedic surgery, including post total knee arthroplasty and anterior cruciate ligament surgery, and chronic knee pain. Many studies have investigated the utility of peripheral nerve stimulation for the management of chronic shoulder pain. Peripheral nerve stimulation also serves as one of the potential non-pharmacologic therapies to treat back pain along with physical therapy, application of transcutaneous electrical neurostimulation unit, radiofrequency ablation, epidural steroid injections, permanently implanted neurostimulators, and surgery. Studies regarding back pain treatment have shown that peripheral nerve stimulation led to significant improvement in all pain and quality-of-life measures and a reduction in the use of opioids. Further studies are needed as the long-term risks and benefits of peripheral nerve stimulation have not been well studied as most information available on the effectiveness of peripheral nerve stimulation is based on shorter-term improvements in chronic pain.

Introduction: Nalbuphine, a synthetic kappa-opioid receptor (KOR) agonist and a partial µ-opioid receptor (MOR) antagonist, has been used for years as an effective analgesic. It has been shown to have a better safety profile than morphine. Considering the long history of use of this drug, it is interesting that only a limited amount of information exists on how gender differences influence nalbuphine responses. In this randomized double-blind comparative trial after major abdominal surgery, the analgesic effects of two doses of continuous intravenous infusion of nalbuphine were evaluated based on gender. Methods: Enrolled patients were divided into four groups (two females and two males with 32 patients in each group). Two of them (groups A1 and A2), one male and one female, received postoperative continuous intravenous infusions of nalbuphine at 2 mg/h via patient-controlled analgesia (PCA). Each patient had the potential of receiving a rescue bolus of 1 mg of nalbuphine with a lock out time of 15 min. The other two groups (groups B1 and B2) received half the infusion dose, 1 mg/h, and half the nalbuphine rescue dose with the PCA pump, 0.5 mg maximum every 15 min as needed. Patients' vital signs, numerical pain rating scores, rescue nalbuphine, and incidence of side effects were assessed immediately after the operation, and every 3 h during the first 12 h. Results: Nalbuphine 2 mg/h dosing led to significantly lower pain scores amongst females compared to males at 6, 9, and 12 h; while the 1 mg/h infusion pain scores were only lower at the 9-h time period. Females receiving the nalbuphine 2 mg dose at 6 h, and the 1 mg dose at 6, 9, and 12-h measurements needed significantly lower doses of rescue nalbuphine. Females on the 1 mg dose experienced significantly more nausea, vomiting, and sedation at the 6-, 9-, and 12-h measurement times. In the multivariate analysis, female gender was a negative predictor at all measurement times. Conclusions: The current study supports the hypothesis that although nalbuphine was found to be an effective and well-tolerated analgesic after major abdominal surgery, females were statistically more responsive than males. Trial Registration: The study was registered at the Pan African Clinical trials Registry PACTR201304000486309, and approved for the Ethical aspects.

Lumbar spinal stenosis (LSS), which often occurs concurrently with degenerative spondylolisthesis (DS), is a common disease in the elderly population, affecting the quality of life of aged people significantly. Notwithstanding the frequently good effect of conservative therapy on LSS, a minority of the patients ultimately require surgery. Surgery for LSS aims to decompress the narrowed spinal canals with preservation of spinal stability. Traditional open surgery, either pure decompression or decompression with fusion, was considered effective for the treatment of LSS with or without DS. However, the long-term clinical outcomes of traditional open surgery are still unclear. Moreover, the disadvantages of conventional open surgery are extensive, examples including tissue injuries or secondary instability, with limited outcomes and significant reoperation rates. With the development and improvement of surgical tools, various minimally invasive spine surgery (MISS) methods, including indirect decompression techniques of interspinous process devices (IPDs) and direct decompression techniques such as microscopic spine surgery or endoscopic spine surgery (ESS), have been updated with enhancement. IPDs, such as Superion devices, were reported to behave with comparable physical function, disability, and symptoms outcomes to laminectomy decompression. As an emerging technique of MISS, ESS has beneficial hallmarks including minimal tissue injuries, reduced complication rates, and shortened recovery periods, thus gaining popularity in recent years. ESS can be classified in terms of endoscopic hallmarks and approaches. Predictably, with the continuous development and gradual maturity, MISS is expected to replace traditional open surgery widely in the surgical treatment of LSS associated with DS in the future.

Introduction: Spinal cord stimulation (SCS) is a commonly utilized therapy for the treatment of neuropathic pain conditions. The Neurostimulation Appropriateness Consensus Committee (NACC) has recommended that the placement of percutaneous SCS leads be performed in an awake patient capable of providing feedback. It is not currently known how commonly this recommendation is adhered to by physicians in clinical practice. This article presents the findings of a survey designed to answer this important question. Methods: We conducted a survey of the active membership of the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the Spine Intervention Society (SIS) regarding practice patterns with SCS therapy. We analyzed the percent of respondents who indicated that they use deep sedation and general anesthesia during SCS placement as well as any reported complications. Results: Many practitioners frequently utilize deep sedation as well as general anesthesia when performing SCS implants. Our findings demonstrate that 77% of physicians reported that they utilize deep sedation for permanent SCS implants at times, and 45% of physicians reported the use of general anesthesia for 10 kHz implants. Additionally, 94% of physicians reported that they have never had a complication related to the use of general anesthesia for a spinal cord stimulator placement. Conclusions: This survey provides initial data on SCS practices among a large cohort of clinicians who utilize SCS. SCS lead placement under deep sedation and general anesthesia appears to be common practice for many physicians who perform implants. This survey should stimulate further research on this topic, given that the current safety guidelines and the rate of physicians reporting the use of deep sedation and general anesthesia for spinal cord stimulator placement remain at odds.

Complex regional pain syndrome (CRPS) is a chronic pain condition often involving hyperalgesia and allodynia of the extremities. CRPS is divided into CRPS-I and CRPS-II. Type I occurs when there is no confirmed nerve injury. Type II is when there is known associated nerve injury. Female gender is a risk factor for developing CRPS. Other risk factors include fibromyalgia and rheumatoid arthritis. Unfortunately, the pathogenesis of CRPS is not yet clarified. Some studies have demonstrated different potential pathways. Neuropathic inflammation, specifically activation of peripheral nociceptors of C-fibers, has been shown to play a critical role in developing CRPS. The autonomic nervous system (ANS) is involved. Depending on whether it is acute or chronic CRPS, norepinephrine levels are either decreased or increased, respectively. Some studies have suggested the importance of genetics in developing CRPS. More consideration is being given to the role of psychological factors. Some association between a history of depression and/or post-traumatic stress disorder (PTSD) and the diagnosis of CRPS has been demonstrated. Treatment modalities available range from physical therapy, pharmacotherapy, and interventional techniques. Physical and occupational therapies include mirror therapy and graded motor imagery. Medical management with non-steroidal anti-inflammatory drugs (NSAIDs) has not shown significant improvement. There have been supporting findings in the use of short-course steroids, bisphosphonates, gabapentin, and ketamine. Antioxidant treatment has also shown some promise. Other pharmacotherapies include low-dose naltrexone and Botulinum toxin A (BTX-A). Sympathetic blocks are routinely used, even if their short- and long-term effects are not clear. Finally, spinal cord stimulation (SCS) has been used for decades. In conclusion, CRPS is a multifactorial condition that still requires further studying to better understand its pathogenesis, epidemiology, genetic involvement, psychological implications, and treatment options. Future studies are warranted to better understand this syndrome. This will provide an opportunity for better prevention, diagnosis, and treatment of CRPS.

Acute and chronic pain are public health issues that clinicians have been battling for years. Opioid medications have been a treatment option for both chronic and acute pain; however, they can cause unwanted complications and are a major contributor to our present opioid epidemic. The sacroiliac (SI) joint is a common cause of both acute and chronic low back pain. It affects about 15–25% of patients with axial low back pain, and up to 40% of patients with ongoing pain following lumbar fusion. Recent advances in the treatment of SI joint pain have led to the development of a wide variety of SI joint fusion devices. These fusion devices seek to stabilize the joints themselves in order that they become immobile and, in theory, can no longer be a source for pain. This is a minimally invasive procedure aimed to address chronic pain without subjecting patients to lengthy surgery or medications, including opioids with the potential for addiction and abuse. Minimally invasive SI fusion can be performed by a lateral approach (i.e., iFuse, Tricor) or posterior approach (i.e., CornerLoc, LinQ, Rialto). The posterior approach requires the patient to be in the prone position but allows for less disruption of muscles with entry. More data are necessary to determine which fusion system may be best for a particular patient. SI fusion devices are a promising way of treating chronic lower back pain related to the SI joint. This narrative review will discuss various types of SI fusion devices, and their potential use in terms of their safety and efficacy.

Purpose of Review: Chronic venous insufficiency is found to some extent in a large proportion of the world’s population, especially in the elderly and obese. Despite its prevalence, little research has been pursued into this pathology when compared to similarly common conditions. Pain is often the presenting symptom of chronic venous insufficiency and has significant deleterious effects on quality of life. This manuscript will describe the development of pain in chronic venous insufficiency, and will also review both traditional methods of pain management and novel advances in both medical and surgical therapy for this disease. Recent Findings: Pain in chronic venous insufficiency is a common complication which remains poorly correlated in recent studies with the clinically observable extent of disease. Although lifestyle modification remains the foundation of treatment for pain associated with chronic venous sufficiency, compression devices and various pharmacologic agents have emerged as safe and effective treatments for pain in these patients. In patients for whom these measures are insufficient, recently developed minimally invasive vascular surgical techniques have been shown to reduce postsurgical complications and recovery time, although additional research is necessary to characterize long-term outcomes of these procedures. Summary: This review discusses the latest findings concerning the pathophysiology of pain in chronic venous insufficiency, conservative and medical management, and surgical strategies for pain relief, including minimally invasive treatment strategies.

Purpose of the Review: Chronic low back pain (CLBP) is a major contributor to societal disease burden and years lived with disability. Nonspecific low back pain (LBP) is attributed to physical and psychosocial factors, including lifestyle factors, obesity, and depression. Mechanical low back pain occurs related to repeated trauma to or overuse of the spine, intervertebral disks, and surrounding tissues. This causes disc herniation, vertebral compression fractures, lumbar spondylosis, spondylolisthesis, and lumbosacral muscle strain. Recent Findings: A systematic review of relevant literature was conducted. CENTRAL, MEDLINE, EMBASE, PubMed, and two clinical trials registry databases up to 24 June 2015 were included in this review. Search terms included: low back pain, over the counter, non-steroidal anti-inflammatory (NSAID), CLBP, ibuprofen, naproxen, acetaminophen, disk herniation, lumbar spondylosis, vertebral compression fractures, spondylolisthesis, and lumbosacral muscle strain. Over-the-counter analgesics are the most frequently used first-line medication for LBP, and current guidelines indicate that over-the-counter medications should be the first prescribed treatment for non-specific LBP. Current literature suggests that NSAIDs and acetaminophen as well as antidepressants, muscle relaxants, and opioids are effective treatments for CLBP. Recent randomized controlled trials also evaluate the benefit of buprenorphine, tramadol, and strong opioids such as oxycodone. Summary: This systematic review discusses current evidence pertaining to non-prescription treatment options for chronic low back pain.

Chronic low back pain affects a significant portion of patients worldwide and is a major contributor to patient disability; however, it is a difficult problem to diagnose and treat. The prevailing model of chronic low back pain has presumed to follow a discogenic model, but recent studies have shown a vertebrogenic model that involves the basivertebral nerve (BVN). Radiofrequency ablation of the BVN has emerged as a possible nonsurgical therapy for vertebrogenic low back pain. The objective of this manuscript is to provide a comprehensive review of vertebrogenic pain diagnosis and our current understanding of BVN ablation as treatment.

Coronary artery bypass grafting (CABG) remains a routine operation despite major advancements in angioplastic procedures. Around 200,000 CABG procedures are performed annually in the U.S. Patients who are not candidates for angioplasty intervention often have advanced coronary disease and comorbidities that raise the risk of heart failure with decreased ejection fraction to around 25%. Over the years, significant developments in various preoperative interventions have occurred; in this paper, we suggest a multidisciplinary preoperative algorithm that can be included in a regularly scheduled multidisciplinary care plan.

End-stage chronic obstructive pulmonary disease (COPD) is the most common indication for single- or double-lung transplantation. Acute native lung hyperinflation (ANLH) is a unique postoperative complication of single-lung transplantation for COPD patients, with incidence varying in the medical literature from 15 to 30%. The diagnosis is made radiographically by contralateral mediastinal shift and ipsilateral diaphragmatic flattening. ANLH can deteriorate into hemodynamic instability, and respiratory impairment can result from compression of the allograft, which can precipitate atelectasis, hypoxemia, and hypercapnia, necessitating specific ventilatory intervention or volume reduction surgery. Currently, there is consensus for a therapeutic role of noninvasive positive pressure ventilation (NIPPV) in acute respiratory failure after lung transplantation as a well-tolerated measure to avoid re-intubation. This manuscript presents a concise review on the diagnosis and treatment of ANLH following unilateral lung transplant, along with a management algorithm created by the authors.

Postoperative nausea and vomiting (PONV) is an undesirable outcome that occurs in up to 30% of patients. Over the years, the cost of treating PONV has decreased due to the availability of cheaper yet effective antiemetics. Limiting PONV development benefits the hospital system as studies have shown that prevention is associated with shorter post-anesthesia care unit (PACU) stays as well as decreased supply costs and staffing burden. The financial burden for prophylaxis against PONV has been shown to be less than what patients are willing to pay to prevent the development of PONV. Studies have also shown that prevention of initial development of PONV limits readmission rates, which is beneficial to both the patient and the hospital. Owing to recent economic analysis and reductions in antiemetic prices, the patient's preference for comfort, the hospital's commitment to providing the best care, and the system's desire for fiscal prudence are aligned. This culminates in recommending PONV prophylaxis for all patients undergoing anesthesia.

Myofascial Pain Syndrome (MPS) is a regional pain disorder that affects every age-group and is characterized by the presence of trigger points (TrPs) within muscles or fascia. MPS is typically diagnosed via physical exam, and the general agreement for diagnostic criteria includes the presence of TrPs, pain upon palpation, a referred pain pattern, and a local twitch response. The prevalence of MPS among patients presenting to medical clinics due to pain ranges anywhere from 30 to 93%. This may be due to the lack of clear criteria and guidelines in diagnosing MPS. Despite the prevalence of MPS, its pathophysiology remains incompletely understood. There are many different ways to manage and treat MPS. Some include exercise, TrP injections, medications, and other alternative therapies. More research is needed to form uniformly-accepted diagnostic criteria and treatments.

Chronic pelvic pain (CPP) in women is defined as noncyclical and persistent pain lasting more than six months perceived to be related to the pelvis. There are many etiologies that can cause CPP, including gynecologic, urologic, gastrointestinal, musculoskeletal, neurologic, and psychosocial. There is a strong association between psychological factors and CPP. It has been noted that almost half of women being treated for CPP report a history of sexual, physical, or emotional trauma. Women with CPP have been noted to have higher rates of psychological disorders in comparison to their peers. For men, the most common etiology for CPP is chronic prostatitis and there are also correlations with psychological disorders. There are many different treatment options for CPP: surgical, pharmacological, and non-pharmacological (alternative therapies). Cognitive-behavioral therapy may be another option when treating chronic pelvic pain syndrome and should be considered.

Angina pectoris is defined as substernal chest pain that is typically exacerbated by exertion, stress, or other exposures. There are various methods of treatment for angina. Lifestyle modification and pharmacological management are considered as conservative treatments. If these medications do not result in the resolution of pain, more invasive approaches are an option, like coronary revascularization. Refractory angina (RA) is differentiated from acute or chronic angina based on the persistence of symptoms despite conventional therapies. Overall, the prevalence of RA is estimated to be 5%–15% in patients with coronary artery disease, which can account for up to 1,500,000 current cases and 100,000 new cases in the United States per year. Spinal cord stimulation treatment is a viable option for patients who are suffering from RA pain and are either not candidates for revascularization surgery or are currently not being well managed on more traditional treatments. Many studies show a positive result.

Lateral epicondylitis (LE), also known as tennis elbow, is the most common cause of elbow pain in adults, with approximately 1–3% of the general population being afflicted. Although the condition is usually self-limiting, pain can be a major hindrance, limiting daily activity and the work capacity of patients. As a result, many treatment options have become available with the aim to shorten the duration of the disease and increase the quality of life. Steroid injections, NSAIDs, topical creams, platelet-rich plasma, physical therapy, and kinesiotaping are considered conservative treatments, while surgical options are last-resort treatments reserved for refractory LE. In this review, we will provide a brief summary of LE and focus on addressing conservative and minimally invasive interventional options for the treatment of LE.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Pharmacogenomics is the study of how genetic differences between individuals affect pharmacokinetics and pharmacodynamics. These differences are apparent to clinicians when taking into account the wide range of responses to medications given in clinical practice. A review of literature involving pharmacogenomics and pain management was performed. The implementation of preoperative pharmacogenomics will allow us to better care for our patients by delivering personalized, safer medicine. This review describes the current state of pharmacogenomics as it relates to many aspects of clinical practice and how clinicians can use these tools to improve patient outcomes.

Total knee arthroplasty (TKA), a common elective surgical procedure, is indicated in patients with knee pain that becomes refractory to nonsurgical interventions, such as weight loss, physical activity, physical therapy, and pharmacologic treatment. However, postoperative chronic pain is frequently reported and may lead to opioid use and dependence. Due to the increasing concern of the overuse of opioids in medical treatments, a search for other viable options is recognized. As a consequence, alternative therapies, such as transcutaneous electrical nerve stimulation (TENS), pulsed radiofrequency (PRF), and spinal cord stimulation (SCS) are being tried to potentially replace traditional opioid use in treating persistent postsurgical pain (PPSP), thus reducing opioid dependence across the nation. Here, we provide a brief overview of persistent pain following TKA procedures, with a particular emphasis on the role of promising therapies, such as TENS, PRF, and SCS for the treatment of post-TKA pain.

This comprehensive review aims to explain the potential impact of coronavirus disease 2019 (COVID-19) on mental wellbeing of healthcare professionals (HCPs). Based on up-to-date research and psychological diagnostic manuals of Diagnostic and Statistical Manual of Mental Disorders, 5th edition and International Classification of Diseases, 11th revision, we describe associated psychological disorders and experiences that may arise related to COVID-19. Appropriate psychological measures are introduced, along with potential methodological limitations. Lastly, resilience building and preventative measures with interventions that may mitigate the impact on mental health of HCPs are described.

Coronavirus disease 2019 (COVID-19) is a new disease with different phases that can be catastrophic for subpopulations of patients with cardiovascular and pulmonary disease states at baseline. Appreciation for these different phases and treatment modalities, including manipulation of ventilatory settings and therapeutics, has made it a less lethal disease than when it emerged earlier this year. Different aspects of the disease are still largely unknown. However, laboratory investigation and clinical course of the COVID-19 show that this new disease is not a typical acute respiratory distress syndrome process, especially during the first phase. For this reason, the best strategy to be applied is to treat differently the single phases and to support the single functions of the failing organs as they appear.

During this coronavirus disease 2019 (COVID-19) pandemic, there is an international call to postpone all elective surgeries. Cardiac surgery carries a combined risk for cardiac patients, who are at risk for higher complications of COVID-19, and healthcare workers. In response to the COVID-19 pandemic, the American College of Surgeons and the American Society of Anesthesiologists recommended a sustained reduction in the rate of new COVID-19 cases for 14 days before the resumption of the elective surgery, but postponing surgery may impact patients’ daily activities and increase the risk the of deterioration of their cardiac condition. We will discuss the risks and benefits of the decision whether to postpone or proceed with elective cardiac surgical procedures during the escalating COVID-19 pandemic considering the specific risk of the cardiac patients, the unique characteristics of the surgery, and the international health system capacity.

The COVID-19 outbreak has influenced the entire health care system, including cardiac surgery. In this review, the authors reveal practical aspects that are important during the COVID-19 pandemic with regards to the safe delivery of cardiac anesthesia.

Chronic pain is typically defined as pain that persists after acute tissue damage and inflammation or as pain that follows a chronic disease process and lasts more than three months. Because of its debilitating impact on the quality of life of patients, recent research aims to investigate the mechanisms behind nociception to discover novel therapeutic agents to alleviate pain. One such target is the neuropeptide calcitonin gene-related peptide (CGRP), which has shown to play an integral role in migraine pathophysiology. Effective treatments of migraines with CGRP antagonists have stimulated our efforts toward checking a possible involvement of CGRP in nonheadache pain conditions such as hypertension, congestive heart failure, Alzheimer's disease, and vascular ischemia. Here, we provide a brief overview of chronic pain, with a particular emphasis on the role of CGRP as a fundamental mediator of nociceptive pain as well as a target for novel therapeutic agents.

Chronic pain syndromes cost the US healthcare system over $600 billion per year. A subtype of chronic pain is neuropathic pain (NP), which is defined as “pain caused by a lesion or disease of the somatosensory system,” according to the International Association for the Study of Pain (IASP). The pathophysiology of neuropathic pain is very complex, and more research needs to be done to find the exact mechanism. Patients that have preexisting conditions such as cancer and diabetes are at high-risk of developing NP. Many NP patients are misdiagnosed and receive delayed treatment due to a lack of a standardized classification system that allows clinicians to identify, understand, and utilize pain management in these patients. Medications like tricyclic antidepressants, serotonin-norepinephrine reuptake Inhibitor (SNRIs), and gabapentinoids are first-line treatments followed by opioids, cannabinoids, and other drugs. There are limited studies on the treatment of NP.

Migraine is a debilitating neurological condition with symptoms typically consisting of unilateral and pulsating headache, sensitivity to sensory stimuli, nausea, and vomiting. The World Health Organization (WHO) reports that migraine is the third most prevalent medical disorder and second most disabling neurological condition in the world. There are several options for preventive migraine treatments that include, but are not limited to, anticonvulsants, antidepressants, beta blockers, calcium channel blockers, botulinum toxins, NSAIDs, riboflavin, and magnesium. Patients may also benefit from adjunct nonpharmacological options in the comprehensive prevention of migraines, such as cognitive behavior therapy, relaxation therapies, biofeedback, lifestyle guidance, and education. Preventative therapies are an essential component of the overall approach to the pharmacological treatment of migraine. Comparative studies of newer therapies are needed to help patients receive the best treatment option for chronic migraine pain.

Acupuncture is a practice based on traditional Chinese medicine, in which needles are used to restore the body's internal balance. Recently, there has been growing interest in the use of acupuncture for various pain conditions. Acupuncture's efficacy in five pain conditions—low back pain (LBP), migraines, fibromyalgia, neck pain, and abdominal pain—was evaluated in this evidence-based, comprehensive review. Based on the most recent evidence, migraine and fibromyalgia are two conditions with the most favorable outcomes after acupuncture. At the same time, abdominal pain has the least evidence for the use of acupuncture. Acupuncture is efficacious for reducing pain in patients with LBP, and for short-term pain relief for those with neck pain. Further research needs to be done to evaluate acupuncture's efficacy in these conditions, especially for abdominal pain, as many of the current studies have a risk of bias due to lack of blinding and small sample size.

Chronic migraine is a particular classification of a headache that is typically unilateral and pulsatile and lasts for at least 3 months. Owing to its high prevalence and detrimental impact on personal, social, and economic aspects of patient lives, much desire has gone into fully understanding the pathogenesis of migraine, and to search for therapeutic agents. In addition to current therapeutics such as triptans, ergotamine, and monoclonal antibodies targeting calcitonin gene-related peptide receptors, vitamin B12 has been investigated for its possible use as a prophylactic agent for migraines. Specifically, the observed effects of vitamin B12 on nitric oxide and homocysteine prompt further investigation of its underlying mechanisms in migraine pathophysiology. In this comprehensive review, we provide a brief overview of migraines and current therapies while focusing on the promising role of vitamin B12 as a possible treatment option for chronic migraine management.

Chronic pain can be recurrent or constant pain that lasts for longer than 3 months and can result in disability, suffering, and a physical disturbance. Related to the complex nature of chronic pain, treatments have a pharmacological and non-pharmacological approach. Due to the opioid epidemic, alternative therapies have been introduced, and components of the plant Cannabis Sativa, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have gained recent interest as a choice of treatment. The exact mechanism for CBD is currently unknown, but unlike the CBD's psychoactive counterpart, THC, the side effects of CBD itself have been shown to be overall much more benign. The current pharmaceutical products for the treatment of chronic pain are known as nabiximols, and they contain a ratio of THC combined with CBD, which has been promising. This review focuses on the treatment efficacy of CBD, THC: CBD-based treatments for chronic pain and adverse events with each.

Chronic pain is a common condition that is being increasingly recognized, diagnosed, and treated in a variety of settings. Opioids can be used to treat chronic pain but at the cost of adverse effects and risk of dependence. Recently, there has been a movement to improve analgesic care in the setting of the opioid epidemic and the overprescribing of opioids, causing over-accessibility, dependence, and large numbers of overdose deaths. Opioid-specific receptors, including the μ, δ, κ, and opioid receptor like-1 (ORL-1) receptors, are each 7-transmembrane spanning proteins, which affect the G-protein and β-arrestin cascades. Each opioid class can act differently on the receptors, resulting in full, partial, or antagonizing effects. This comprehensive review looks at different agents in major classes, nonselective and mixed/partial agonists/antagonists, including the nonselective partial agonists, levorphanol and tramadol. Mixed partial agonists/antagonists include buprenorphine, pentazocine, nalbuphine, and butorphanol. Oliceridine is the only current selective partial agonist that agonizes specific pathways to promote analgesic effects and discourage adverse effects.

Primary osteoarthritis (OA) hinders an aging global population as one of the leading causes of years-lost-to-disability (YLD). OA in most patients is considered to be an overuse injury that results in degenerative inflammation of the joints with the associated formation of bony outgrowths. Due to the escalating nature of this chronic pain disease, treatment management for OA can initially begin with a more conservative approach. It can eventually lead to more invasive surgical procedures. At present, the standard of care remains initial conservative management with lifestyle changes, including weight loss with concurrent anti-inflammatory regimens. Injections are frequently used for the escalation of care, but a significant number of patients ultimately resort to total knee arthroplasty. This review will focus specifically on knee OA, providing a brief overview of risk factors and early management and in-depth exploration of the invasive interventions that can offer symptomatic relief and return of function.

Reclassification of chronic pain as a disease may be helpful because patients with chronic pain require significant treatment and rehabilitation with a clear diagnosis. This can help address critical factors including suffering, quality of life, participation, and with family and social life, which continue to become more important in evaluating the quality of the health care we give our patients today. During the past decade of the opioid epidemic, methadone was the primary treatment for opioid addiction until buprenorphine was approved. Buprenorphine's high-affinity partial agonist properties make it a good alternative to methadone due to lower abuse potential and safer adverse effect profile while maintaining significant efficacy. Expanded out-patient prescribing options have allowed physician and physician extenders such as physician assistants and nurse practitioners to treat these patients that otherwise would have been required to utilize methadone. With unique pharmacological properties, buprenorphine is a safe and effective analgesic for chronic pain. The literature for buprenorphine shows great potential for its utilization in the treatment of chronic pain.

Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, healthcare workers, health systems, as well as economies. While, healthcare systems are globally operating at maximum capacity, healthcare workers and especially anesthesia providers are facing extreme pressures, something that is also leading to declining availability and increasing stress. In this regard, it is extremely concerning the fact that some regions worldwide have reported up to 20% of their cases to be healthcare workers. When considering that the global case fatality rate may be as much as 5.4%, these numbers are concerning and unacceptable. As this pandemic accelerates, access to personal protective equipment for health workers is a key concern since at present, healthcare workers are every country's most valuable resource in the fight against COVID-19. Governments and heath organizations should take care of their staff and support them in any way possible. This review aims to describe the current situation anesthesia providers are facing in the setting of COVID-19 and provide solutions and evidence on important concerns, including which guidance to follow, the level of equipment that is adequate, and the level of protection they need for every patient being administered an anesthetic.

Although pain treatment has been described as a fundamental human right, the Coronavirus disease 2019 (COVID-19) pandemic forced healthcare systems worldwide to redistribute healthcare resources toward intensive care units and other COVID-19 dedicated sites. As most chronic pain services were subsequently deemed non-urgent, all outpatient and elective interventional procedures have been reduced or interrupted during the COVID-19 pandemic in order to reduce the risk of viral spread. The shutdown of pain services jointly to the home lockdown imposed by governments has affected chronic pain management worldwide with additional impact on patients' psychological health. Therefore, the aim of this review is to analyze the impact of COVID-19 pandemic on chronic pain treatment and to address what types of strategies can be implemented or supported in order to overcome imposed limitations in delivery of chronic pain patient care.

Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and Drug Administration (FDA) after multiple studies showed that it was well-tolerated, safe, and effective in the treatment of migraines. Further research is needed to elucidate the long-term effects of fremanezumab and CGRP-antagonists in general, and additional data is required in less healthy patients to estimate its effects in these populations and potentially increase the eligible group of recipients. This is a comprehensive review of the current literature on the efficacy and safety of fremanezumab for the treatment of chronic migraine. In this review we provide an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarize the evidence for fremanezumab as a treatment for migraine.

Purpose of Review: This is a comprehensive literature review of the available evidence and techniques of foot injections for chronic pain conditions. It briefly describes common foot chronic pain syndromes and then reviews available injection techniques for each of these syndromes, weighing the available evidence and comparing the available approaches. Recent Findings: Foot and ankle pain affects 20% of the population over 50 and significantly impairs mobility and ability to participate in activities of daily living (ADLs), as well as increases fall risk. It is commonly treated with costly surgery, at times with questionable efficacy. Injection therapy is challenging when the etiology is anatomical or compressive. Morton’s neuroma is a budging of the interdigital nerve. Steroid, alcohol, and capsaicin injections provide some benefit, but it is short lived. Hyaluronic acid (HA) injection provided long-term relief and could prove to be a viable treatment option. Achilles tendinopathy (AT) is most likely secondary to repeat tendon stress—platelet-rich-plasma (PRP) and prolotherapy have been trialed for this condition, but more evidence is required to show efficacy. Similar injections were trials for plantar fasciitis and achieved only short-term relief; however, some evidence suggests that PRP injections reduce the frequency of required therapy. Tarsal tunnel syndrome, a compressive neuropathy carries a risk of permanent neural injury if left untreated. Injection therapy can provide a bridge to surgery; however, surgical decompression remains the definitive therapy. When the etiology is inflammatory, steroid injection is more likely to provide benefit. This has been shown in several studies for gout, as well as osteoarthritis of the foot and ankle and treatment-refractory rheumatoid arthritis. HA showed similar benefit, possibly due to anti-inflammatory effects. Stem cell injections may provide the additional benefit of structure restoration. Summary: Chronic foot pain is common in the general population and has significant associated morbidity and disability. Traditionally treated with surgery, these are costly and only somewhat effective. Injections provide an effective alternative financially and some evidence exists that they are effective in pain alleviation. However, current evidence is limited and the benefit described from injection therapy has been short-lived in most cases. Further studies in larger populations are required to evaluate the long-term effects of these treatments.