A Comprehensive Review and Update of Post-surgical Cutaneous Nerve Entrapment.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding post-surgical cutaneous nerve entrapment, epidemiology, pathophysiology, and clinical presentation. It focuses mainly on nerve entrapment leading to chronic pain and the available therapies. RECENT FINDINGS: Cutaneous nerve entrapment is not an uncommon result (up to 30% of patients) of surgery and could lead to significant, difficult to treat chronic pain. Untreated, entrapment can lead to neuropathy and damage to enervated structures and musculature, and significant morbidity and financial loss. Nerve entrapment is defined as pressure neuropathy from chronic compression. It causes changes to all layers of the nerve tissue. It is most significantly associated with hernia repair and other procedures employing a Pfannenstiel incision. The initial insult is usually incising of the nerve, followed by formation of a neuroma, incorporation of the nerve during closing, or constriction from adhesions. The three most commonly involved nerves are the iliohypogastric, ilioinguinal, and genitofemoral nerves. Cutaneous abdominal nerve entrapment could occur during thoracoabdominal surgery. The presentation of nerve entrapment usually involved post-surgical pain in the territory innervated by the trapped nerve, possibly with radiation that tracks the nerve course. Once a suspected neuropathy is identified, it can be diagnosed with relief in pain after a nerve block has been instilled. Treatment is usually started with pharmaceutical solutions, topical first and oral if those fail. Most patients require escalation to a second line of treatment and see good result with injection therapy. Those that require further escalation can choose between ablation and surgical therapies. Post-surgical nerve entrapment is not uncommon and causes serious morbidity and financial loss. It is underdiagnosed and thus undertreated. Preventing nerve entrapment is the best treatment; when it does occur, options include topical and oral analgesics, nerve blocks, ablation therapy, and repeat surgery.

Local anesthetics counteract cell proliferation and migration of human triple-negative breast cancer and melanoma cells.

In different retrospective studies, a protective role of regional anesthetics in reducing cancer recurrence after surgery was indicated. Accordingly, it has been previously demonstrated a protective effect of anesthetics in breast cancer cells and in other types of cancer. On the other hand, how anesthetics influence cancer needs in-depth investigations. For this purpose, two different human cancer cell lines, MDA-MB-231, triple-negative breast cancer, and A375, melanoma, were used in this study. By means of Western blotting and immunofluorescence and terminal deoxynucleotidyl transferase dUTP nick end labeling analyses, the signal transduction pathways activated by the anesthetics, such as ropivacaine and levobupivacaine, were analyzed. The data obtained demonstrated that both anesthetics are able to counteract cell proliferation by positively modulating cell death signaling and by decreasing cell proliferation and survival pathways.

The concern about ACE/ARB and COVID-19: Time to hold your horses!

Concern about coronavirus 2019 (COVID-19) morbidity and mortality has drawn attention to the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) because the SARS-CoV-2 uses the ACE2 receptor as its point of entry into the body. It is not clear if and to what degree the SARS-CoV-2 virus affects the renin-angoiotensin system. Early studies from China which speculated on the role of ACE inhibition and ARBs did not evaluate the drug regimens. A vast body of evidence supports the use of ACE inhibitors and ARBs in hypertensive patients and patients with heart failure, and very little evidence has been acquired about their role in COVID-19. There is good evidence in support of the use of ACE inhibitors and ARBs in indicated patients with hypertension and heart failure, and clinicians should be reticent about abruptly withdrawing these drugs based on a paucity of evidence.

Epidemiology of Chronic Pain in the Latium Region, Italy: A Cross-Sectional Study on the Clinical Characteristics of Patients Attending Pain Clinics.

In Italy, chronic pain affects more than a quarter of the population, whereas the average European prevalence is 21%. This high prevalence might be due to the high percentage of Italian people who do not receive treatment, even after the passing of law 38/2010 (the right to access pain management in Italy), which created a regional network for the diagnosis and treatment of noncancer chronic pain. Italian epidemiologic studies on chronic pain are scanty, and this observational, multicenter, cross-sectional study is the first to investigate the clinical characteristics of patients who attended the pain management clinics in the Latium Region, Italy, for the management of their noncancer chronic pain. A total of 1,606 patients (mean age 56.8 years, standard deviation ± 11.4), 67% women, were analyzed. Severe pain was present in 54% of the sample. Women experienced pain and had it in two or more sites more often than men (57% vs. 50%, p = .02; and 55.2% vs. 45.9%, p < .001, respectively). Chronic pain was musculoskeletal (45%), mixed (34%), and neuropathic (21%). In more than 60% of the cases, chronic pain was continuous, and in 20% it had lasted for more than 48 months; long-lasting pain was often neuropathic. Low back (33.4%) and lower limbs (28.2%) were the main locations. Severe intensity of pain was statistically significantly associated with female gender (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.06-1.84); with International Classification of Diseases, Ninth Revision, codes for chronic pain syndrome (OR 2.14; 95% CI 1.55-2.95); and with continuous pain (OR 2.02; 95% CI 1.54-2.66). Neuropathic pain and mixed pain were significantly associated with number of sites, and a trend seemed to be present (OR 2.11 and 3.02 for 2 and 3 + sites; 95% CI 1.59-2.79 and 2.00-4.55, respectively).

Influence of the Menstrual Cycle Phase on Pain Perception and Analgesic Requirements in Young Women Undergoing Gynecological Laparoscopy.

CONTEXT: The influence of the gonadal hormones on some aspects of the human physiology has been studied with uncertain results. Still a confusion exists in relation to the real effects of the female hormones on the perception of pain. The existing data refer mainly to experimental studies and have provided results not always useful in the clinical practice. DATA SOURCE: This study was designed to detect whether there are differences in the perception of the postoperative pain in women, during two clearly defined phases of hormonal asset: luteal and follicular phases. CONCLUSION: The results of this study have demonstrated that in postoperative female patients pain is perceived significantly more in the luteal phase of the menstrual period, than in the follicular phase. This could suggest that female in child-bearing age should be scheduled for elective surgery preferentially during the follicular phase, unless differently necessary. It would guarantee a more comfortable postoperative period, with reduced necessity of analgesics.

Degenerative Joint Diseases and Neuroinflammation.

Rheumatic and joint diseases, as exemplified by osteoarthritis and rheumatoid arthritis, are among the most widespread painful and disabling pathologies across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is, in particular, on its way to becoming the fourth leading cause of disability worldwide by 2020, with the rising incidence of obesity in addition to age being important factors. It is estimated that 25% of osteoarthritic individuals are unable to perform daily activities. Accompanying osteoarthritis is rheumatoid arthritis, which is a chronic systemic disease that often causes pain and deformity. At least 50% of those affected are unable to remain gainfully employed within 10 years of disease onset. A growing body of evidence now points to inflammation, locally and more systemically, as a promoter of damage to joints and bones, as well as joint-related functional deficits. The pathogenesis underlying joint diseases remains unclear; however, it is currently believed that cross-talk between cartilage and subchondral bone-and loss of balance between these two structures in joint diseases-is a critical element. This view is amplified by the presence of mast cells, whose dysregulation is associated with alterations of junction structures (cartilage, bone, synovia, matrix, nerve endings, and blood vessels). In addition, persistent activation of mast cells facilitates the development of spinal neuroinflammation mediated through their interaction with microglia. Unfortunately, current treatment strategies for rheumatic and articular disease are symptomatic and do little to limit disease progression. Research now should be directed at therapeutic modalities that target osteoarticular structural elements and thereby delaying disease progression and joint replacement.

Low back pain in a natural disaster.

UNLABELLED: Low back pain is usually self-limited. The transition from acute to chronic LBP is influenced by physical and psychological factors. Identification of all contributing factors, in a mass emergency setting, differentiating primary and secondary life-threatening forms of LBP, is the best approach for success. Aims of the present report were to estimate the prevalence of LBP in population afferent to four advanced medical presidiums (AMPs) during postseismic emergency period and to evaluate frequency of use, types of pain killers administered to patients and short-term efficacy of them. METHODS: Study was carried out in four AMPs during the first 5 weeks after the earthquake. Site, type of eventual trauma, pain intensity during LBP episode by Verbal Numerical Rating Scale (vNRS) were registered. Diagnosis of primary or secondary LBP was made on the basis of clinical features and therapeutic treatment was also analyzed. RESULTS: The prevalence of acute LBP was 4.9% (95%, IC 3.7 to 6.4), among 958 first accesses to AMP, representing 14.1% (95%, IC 10.8 to 18.3) of cases on the total of 322 patients treated for all pain conditions. Episodes of relapsed LBP in chronic pre-existing LBP represented the 40% (n = 19) of cases, while the first episode was present in 60% of patients (n = 28). Pain treatment was effective with a significant reduction in vNRS in short term evaluation. CONCLUSIONS: The emotional stress induced by natural disaster tends to heighten norepinephrine and sympathetic nervous system activity, which may further amplify nociception through peripheral or central mechanisms that result in consistent prevalence of primary NSLBP and become potential risk factor for pain chronicization.

Acute Care Surgery: Navigating Recent Developments, Protocols, and Challenges in the Comprehensive Management of Surgical Emergencies.

Acute care surgery (ACS) is a crucial medical field that specifically deals with the rapid treatment of surgical emergencies. This investigation encompasses the most recent progress, procedures, and obstacles in ACS, utilizing various sources such as scholarly articles, clinical trials, and expert statements. The development of ACS as a specialized field is a significant area of concentration, particularly emphasizing its contribution to improving patient care. An examination is conducted on the efficacy of contemporary triage systems and prompt response mechanisms, specifically in diminishing the incidence of illness and death rates associated with illnesses such as trauma, acute appendicitis, and obstructed viscera. The emphasis is placed on the surgical protocols and principles that form the basis of ACS. Examining regional and international approaches provides insight into the distinctions and commonalities in surgical techniques. An assessment is conducted to determine the effects of the transition to minimally invasive procedures on patient outcomes, recuperation periods, and healthcare expenses. The assessment also examines the logistical obstacles that ACS encounters, such as resource allocation and managing diverse teams. The examination focuses on the delicate equilibrium between prompt decision-making and care grounded in evidence. It also evaluates the possible contribution of technical breakthroughs such as telemedicine and AI to improving patient care and overcoming current obstacles. The topic of training and education for surgeons in ACS is of utmost importance and requires careful consideration. The evaluation evaluates the sufficiency of existing educational frameworks and the necessity of specific training to equip surgeons for the requirements of ACS. This analysis explores the current discourse surrounding the standardization of ACS training, considering its potential ramifications for the future of surgical procedures. Exploring ethical and legal problems in ACS also includes situations when prompt decision-making may clash with patient autonomy and informed consent. The significance of proficient communication with patients and their families during emergency surgical scenarios is underscored, emphasizing the necessity for ethical awareness and interpersonal aptitude. The investigation of ACS demonstrates its dynamic character, signifying notable advancements while recognizing enduring obstacles. Continual research, interdisciplinary collaboration, and policy adjustments are necessary to improve ACS procedures. This thorough investigation offers valuable insights for professionals and researchers, facilitating future progress in managing surgical crises.

Hyperkalemia: Pharmacotherapies and Clinical Considerations.

Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There are several drugs, both old and new, that can additionally aid in the reduction of serum potassium levels. The present investigation evaluated some of these different drugs, including sodium polystyrene sulfonate (SPS), sodium zirconium cyclosilicate (SZC), and patiromer. These drugs each have increased selectivity for potassium and work primarily in the gastrointestinal (GI) tract. Each of these medications has unique benefits and contraindications. Clinicians must be aware of these medications when managing patients with hyperkalemia.

Cefiderocol (Fetroja) as a Treatment for Hospital-Acquired Pneumonia.

With increasing resistance to conventional antibiotic treatments, especially among gram-negative bacilli, the search for new antibiotics has become critical on a global scale. Among infections with multidrug-resistant bacteria is hospital-acquired pneumonia (HAP), which is nosocomial pneumonia in patients who have been hospitalized for more than 48 hours. HAP carries a high mortality rate and continues to be a challenge with regard to adequate treatment. The typical multidrug-resistant gram negatives found in HAP include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Many new antibiotics have been studied and tested against these pathogens as possible solutions, and the search continues. Cefiderocol, a novel siderophore cephalosporin, is effective against these pathogens. Cefiderocol is an iron-chelating agent that makes use of iron pumps on the membrane of bacteria via a catechol moiety on the C3 side chain of the molecule. This allows for easy access into the cytoplasm, where it can inhibit peptidoglycan synthesis by binding to penicillin-binding proteins. Cefiderocol displays linear pharmacokinetics and is mainly excreted through the kidneys. It is well tolerated in healthy individuals but may need adjustments of dosage in patients with impaired renal function. Studies have shown that both healthy subjects and those with impaired renal function experienced some adverse effects, including nausea, diarrhea, abdominal pain, and increased creatinine kinase; however, these adverse effects were limited and experienced in placebo groups. It has demonstrated efficacy in treating infections caused by many multidrug-resistant gram-negative pathogens and has demonstrated high stability against many classes of b-lactamases. There have been multiple phase 3 trials, such as the CREDIBLE-CR trial and the APEKS-NP trial, that demonstrated efficacy in treated nosocomial pneumonia caused by multidrug-resistant gram negatives, such as carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, compared to the best available treatment. While clinical data remain limited, a few studies are showing clinical efficacy and few adverse effects. Cefiderocol demonstrated effectivity in treating multidrug-resistant gram-negative pneumonia in patients with multiple comorbidities, such as chronic kidney disease, chronic-obstructive pulmonary disease, and diabetes mellitus. Cefiderocol shows promise as a novel antimicrobial agent in treating multidrug-resistant gram-negative in HAP.

Treating Pulmonary Arterial Hypertension With Sotatercept: A Meta-Analysis.

Pulmonary arterial hypertension (PAH) results from proliferative remodeling and narrowing of the pulmonary vasculature. Sotatercept is a first-in-class fusion protein that has recently garnered attention for showing improvements in patients with PAH. This meta-analysis of randomized controlled trials (RCTs) assesses the overall efficacy of Sotatercept in treating PAH. PubMed, Google Scholar, and Clinicaltrials.gov were searched using relevant keywords and MeSH terms. Studies were included if RCTs compared Sotatercept with placebo in patients with PAH. Our comprehensive literature search yielded 3,127 results, of which two RCTs with 429 patients were included in this meta-analysis. The patients were on background therapy for PAH. Results of the meta-analysis show that when compared with placebo, Sotatercept improved the six-minute walk distance (mean difference [MD] 34.99; 95% confidence interval [CI] 19.02-50.95; P < 0.0001), the World Health Organization (WHO) functional class (odds ratio [OR] 2.50; 95% CI 1.50-4.15; P = 0.0004), and pulmonary vascular resistance (PVR, MD -253.90; 95% CI -356.05 to -151.75; P < 0.00001). However, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP, MD -1563.14; 95% CI -3271.93 to 145.65; P = 0.07) was not statistically significant in the Sotatercept group versus placebo. In conclusion, Sotatercept improves the six-minute walk distance, WHO functional class, and PVR in patients with PAH receiving background therapy. However, the effect on NT-proBNP levels was not statistically significant. More research is needed to assess the clinical relevance of these findings.

Non-steroidal Anti-inflammatory Drug (NSAID)-, Potassium Supplement-, Bisphosphonate-, and Doxycycline-Mediated Peptic Ulcer Effects: A Narrative Review.

Peptic ulcers are a common condition that arises from an imbalance between acid production and gastroduodenal protective factors. Various drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), potassium supplements, bisphosphonates, and doxycycline, can increase the development of peptic ulcers. NSAIDs are one of the most common medications prescribed for pain relief, and they also inhibit the formation of cyclooxygenase-1 (COX-1). COX-1 helps in the production of mucus that lines the stomach, so by inhibiting COX-1, NSAIDs reduce the mucus produced by the stomach and increase the likelihood of gastric ulcer formation. Additionally, NSAIDs are acidic, and increasing the amount of any acid in the stomach can result in promoting ulcer development. Potassium supplements are used to reduce the effects of hypertension, decrease the development of kidney stones, and treat hypokalemia. The various types of transporters and channels used to move potassium across cell membranes increase hydrogen being pumped, increasing gastric acid production and ulcer formation. Bisphosphonates are used to treat a variety of skeletal disorders that require inhibition of osteoclast activity. Nitric oxide (NO) has been shown to have a therapeutic effect on gastric ulcers, and some bisphosphonates have been shown to decrease the production of nitric oxide, resulting in increased damage to the gastric mucosa. Finally, doxycycline is a broad-spectrum tetracycline antibiotic that is typically used to treat anthrax poisoning, skin lesions, and sexually transmitted diseases. A harmful adverse effect of doxycycline is the formation of peptic and gastric ulcers related to the drug being highly acidic once it has dissolved.

The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of flares via disease-modifying therapy. Primary drug therapies for acute flare include corticosteroids to limit inflammation and symptomatic management, depending on symptoms. Several different drugs have been recently approved for use in modifying the course of the disease, including a group of medications known as fumarates (e.g., dimethyl fumarate, diroximel fumarate, monomethyl fumarate) that have been shown to be efficacious and relatively safe. In the present investigation, we review available evidence focused on monomethyl fumarate, also known as Bafiertam®, along with bioequivalent fumarates for the long-term treatment of relapsing-remitting multiple sclerosis.

Pain and natural disaster.

The treatment for pain in emergency medicine is a matter of increasing interest. Available data indicate that in both normal conditions and during major-emergencies, the majority of healthcare providers are culturally and professionally unprepared to adequately treat acute pain conditions. In case of natural disasters, opioid drugs are often unavailable. Moreover, no guidelines or validated protocols provide adequate indications for the treatment for pain in case of massive emergencies. Training of the medical and nursing staff, in both formal and continuing, or on-the-job education is needed to adequately face a devastating emergency. Unfortunately, there is an inadequate level of training among healthcare professionals, even in highly seismic areas, and the source of aid is frequently limited, especially in the immediate aftermath of a disaster to those already present at the scene. Pain inadequately treated may modify the characteristics of the pain itself. Pain is no longer considered just a symptom, but itself becomes an autonomous pathology heavily influencing the social life and psycho-social aspects of a person. In the disastrous situation following an earthquake, an inadequate treatment of pain was the major violation of the psycho-physical integrity of individuals and a severe violation of their rights, as human beings and patients.

Duloxetine and pregabalin for pain management in multiple rheumatic diseases associated with fibromyalgia.

The fibromyalgia syndrome (FMS) is characterized by chronic and widespread musculoskeletal pain and soreness accompanied by sleep disorders, chronic fatigue and affective disorders. FMS is often associated with other forms of immuno-rheumatic diseases. Although FMS pathophysiology is still not fully understood, a number of neuroendocrine, neurotransmission and neurosensitive disorders might generate a mechanism for the elicitation of pain by "central sensitization," which is common to many other painful conditions. The present case describes the success of a therapeutic scheme, which associates two different pharmacological classes, anticonvulsants and new-generation antidepressants, when FMS complicates a rare pathology called Cogan's syndrome. The association of two drugs might noticeably affect the molecular mechanisms of difficult pain, thus solving painful conditions of multifactorial origin.

Guillain-Barré Syndrome Induced by Vaccination Against COVID-19: A Systematic Review and Meta-Analysis.

Guillain-Barré syndrome (GBS) is a rare but serious immune-mediated neurological condition characterized by damage to the peripheral nervous system. Two-thirds of cases of GBS are diagnosed following infection; however, vaccination has also been linked to GBS pathogenesis. The aim of this systematic review and meta-analysis was to establish the prevalence of GBS following vaccination against the SARS-CoV-2 virus, which causes COVID-19, describe the clinical and neurophysiological characteristics, and identify potential determinants. A systematic review of the literature regarding post-vaccination GBS was conducted using the PubMed database. Seventy papers were included. The pooled prevalence of GBS after vaccination against COVID-19 per has been established to be 8.1 (95% CI 30-220) per 1,000,000 vaccinations. Vaccination with vector vaccines - but not mRNA - has been associated with an increased risk of GBS. More than 80% of the patients developed GBS within 21 days following the first dose of the vaccination. The interval between the vaccination and GBS was shorter in patients who were vaccinated with mRNA versus vector vaccines (9.7±6.7 days versus 14.2±6.6 days). Epidemiological findings regarding post-vaccination GBS revealed a higher prevalence in males and people between the ages of 40 and 60 years, with a mean age of 56.8±16.1 years. The most common type was the acute inflammatory demyelinating polyneuropathy type. Most cases responded well to treatment. In conclusion, vaccination against COVID-19 with vector vaccines seems to increase the risk of GBS. GBS occurring following vaccination does differ in characteristics from GBS during the pre-COVID-19 era.

Bridging Old and New in Pain Medicine: An Historical Review.

Pain is both one of the oldest complaints known to medicine and a field for some of medicine's latest breakthroughs and innovations. Pharmacologic treatment of pain is one of the oldest remedies, and opioids have been used since ancient times as an effective pain reliever but with certain specific risks for abuse. Greater knowledge of opioids led to a more thorough understanding of the complexities of pain, which may have any number of mechanisms. A greater understanding of nerve fibers and pain signaling led to the development of more drugs and the more targeted delivery of analgesics using the hollow needle. The hollow needle changed pain treatment and led to percutaneous injections and what would later become interventional pain medicine with regional anesthesia and nerve blocks. Today, imaging can be combined with interventional techniques for more precise localization of nerves for diagnosis and treatment. The role of artificial intelligence in interventional pain medicine, especially in imaging for interventional procedures, remains unknown but will likely become extremely beneficial.

What's New in Neuropathy?

Neuropathic pain presents diagnostic and treatment challenges. Despite recent advances in our understanding of the diagnosis and treatment of neuropathy, much remains to be elucidated. Familiar with neuropathy is the paradox that aberrant nerve signaling causes both sensory loss and pain. Voltage-gated sodium channels play an important role in neuronal electrogenesis and communication among neurons, and their dysregulation leads to hyperexcitability and pain. While numerous validated diagnostic assessment tools are available for neuropathy, patients often experience a diagnostic delay about the cause of their neuropathy. New research is defining more specific types of neuropathy beyond peripheral and central forms. The prevalence of pain varies by type of neuropathy, with chronic idiopathic axonal polyneuropathy associated with the highest proportion of patients experiencing pain. In the majority of types, it exceeds 50%. Gluten neuropathy, a form of peripheral neuropathy, is a new diagnostic consideration. It may require electrochemical conductance testing of hands and feet to test for sudomotor dysfunction. Among those with serologically confirmed gluten sensitivity or celiac disease, gluten neuropathy is a common neurological manifestation and may be addressed at least partially by a gluten-free diet. In Greece, a new neuropathic pain registry was created in 2014 in order to help gather data from real-world neuropathic pain patients. While still in its earliest phase, this registry has already produced demographic and treatment data that suggest suboptimal prescribing and less than recommended use of interventional procedures. Awareness campaigns are underway to encourage more Greek pain clinics to participate in this important registry.

Looking Back, Moving Forward in Pain Medicine.

Pain is an ancient medical complaint and a clinical riddle that has never been entirely solved. Looking back into history was the springboard to a look into the future of pain medicine. This article was based on a series of presentations given in a recent congress (May 2023) and represents the research, views, and opinions of the authors. Opium has been used for millennia to treat pain, but when it gained broad use in the United States in the 1980s and 1990s, it was so vastly overprescribed and mis-prescribed that it led to a public health crisis. This, in turn, led to the reaction where opioids at times were under-prescribed, leaving out many patients who may have benefited from opioids while leaving many legacy pain patients to manage withdrawal on their own and with few analgesic options. Cannabinoids (CB) were likewise widely used for various conditions, including pain, but were outlawed in the 20th century, only to be brought back as a potential analgesic agent. Interventional pain medicine is a developing discipline and has reinforced the concept of the interdisciplinary pain clinic. It plays an increasingly important part in modern medicine overall, especially with the support of ultrasound, for both diagnosis and therapy. Today, the views about pain have changed. Anyone has accepted that pain is not purely a physical phenomenon but a biopsychosocial phenomenon that occurs within a cultural context. Pain management remains a small but vitally important medical subspecialty that is critical from a functional enablement and population health perspective, which is helping to navigate new therapeutic targets, new drugs and routes of administration, greater understanding of pain psychology, and new technologies. Pain control today means early intervention, functional enablement through pain alleviation, educating patients about pain management, and minimizing the transition from acute to chronic pain.

Answering Big Questions in Pain Medicine.

The future of pain medicine is marked by many questions. What can other nations around the world learn from the opioid crisis that is still affecting the United States? The American opioid experience was mischaracterized and wrongly described, and its causes were misdiagnosed from the outset, leading to its mismanagement and the abandonment of many chronic pain patients to their suffering. There are a few new drugs in the analgesic armamentarium. What new targets do we have in pain medicine? There are many breakthroughs, discoveries, and potential new targets that could add to our analgesic prescribing choices. These include sigma receptors, d-amino acid oxidase, endoplasmic reticulum stress receptors, histone deacetylase, and others. Neuromodulation had been used with varying degrees of success for years, but with a simplistic approach based on the gate theory of pain. Despite our familiarity with neuromodulation and spinal cord stimulators, neuromodulation research indicates that the activation of glial cells may activate the immune system and enhance analgesia. Neuromodulation studies have concentrated on how electricity affects neuronal activity rather than how electrical activity could reduce pain. There are still more frontiers in our battle against pain and some promising avenues for treatments. This narrative review will try to summarize what can be done from the perspective of recent technological and pharmacological developments.