Effect of Sodium-Glucose Cotransporter 2 Inhibitors on the 24-Hour Ambulatory Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension: An Updated Meta-Analysis.

OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes mellitus (DM) treatment, have shown potential benefits beyond glycemic control, including a positive impact on the blood pressure (BP). This meta-analysis aimed to evaluate their effects on patients with type 2 DM and hypertension. METHODS: We searched the PubMed, Google Scholar, and Cochrane databases for relevant randomized controlled trials published until May 31, 2023. Ten randomized controlled trials involving participants with confirmed type 2 DM were selected. The intervention group received SGLT2i, whereas the control group received a placebo or standard care. The primary outcomes were the 24-hour ambulatory systolic BP (SBP) and diastolic BP (DBP). RESULTS: The results showed a significant reduction in the 24-hour ambulatory SBP (weighted mean difference, -5.08 mm Hg; 95% confidence interval, -7.02 to -3.14; P <.00001) and DBP (weighted mean difference, -2.73 mm Hg; 95% confidence interval, -4.25 to -1.20; P =.0005) with the use of SGLT2i compared with that using the placebo. However, a high-heterogeneity level was observed in both analyses (SBP, I2 = 83%; DBP, I2 = 91%). Sensitivity analysis excluding specific studies reduced heterogeneity while maintaining statistically significant and clinically relevant reductions in the BP. CONCLUSION: In conclusion, this meta-analysis proves that SGLT2i significantly reduce the 24-hour ambulatory BP. SGLT2i may be considered an effective treatment option for lowering the BP in addition to standard care in patients with hypertension and type 2 DM.

Immune Competence and Pain: A Narrative Review.

PURPOSE OF REVIEW: This review aims to summarize current knowledge on the pathophysiology of pain and the role of neuro-immune crosstalk in the development of acute and chronic pain (CP). Specifically, the review focuses on the role of immune cells involved in the innate and acquired immune response, emphasizing their bidirectional interactions with the nervous systems and discussing the implications of this crosstalk on acute and CP management. RECENT FINDINGS: In the last two decades, multiple studies have uncovered the important role of the immune system in initiating, maintaining, and resolving pain stimuli. Furthermore, researchers discovered that the immune system interacts tightly with the nervous system, creating a bidirectional crosstalk in which immune cells influence the response of peripheral and central nerve fibers while neurotransmitters and neuropeptides released by nociceptors directly and indirectly modulate the immune response. The neuro-immune crosstalk in acute and CP is a complex and not fully understood process that comprise the interactions of multiple diverse molecules, bidirectional interferences, and numerous redundant processes. Despite the complexity, important steps have been taken in recent years toward explaining the specific roles of each immune cell type and molecule in the initiation, maintenance and resolution of pain. These findings may set the basis for innovative therapeutic options that target the immune system, overcoming the limitations of current treatments in providing pain relief and the disadvantages associated with opioid therapy.

Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review.

PURPOSE OF REVIEW: Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens. RECENT FINDINGS: However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

Unraveling the Complex Web of Fibromyalgia: A Narrative Review.

Fibromyalgia is a complex and often misunderstood chronic pain disorder. It is characterized by widespread musculoskeletal pain, fatigue, and heightened sensitivity, and has evolved in diagnostic criteria and understanding over the years. Initially met with skepticism, fibromyalgia is now recognized as a global health concern affecting millions of people, with a prevalence transcending demographic boundaries. The clinical features and diagnosis of fibromyalgia encompass a range of symptoms beyond pain, including sleep disturbances and cognitive difficulties. This study emphasizes the importance of a comprehensive evaluation for accurate diagnosis, considering the shift from tender point reliance to a more holistic approach. Etiology and pathophysiology involve genetic predisposition, neurotransmitter dysregulation, central sensitization, and immune system involvement. Risk factors such as gender, age, family history, and comorbid conditions contribute to susceptibility. The impact on quality of life is profound, affecting physical and social aspects, often accompanied by mood disorders. Management approaches include pharmacological interventions, non-pharmacological therapies, lifestyle modifications, and alternative treatments. This study also delves into emerging research, exploring advances in neurobiological understanding, brain imaging, genetic markers, glutamate modulation, cannabinoids, gut microbiome, and digital health tools for fibromyalgia management. Overall, this study provides a nuanced and up-to-date overview of the complexities surrounding fibromyalgia, aiming to enhance understanding and support for individuals grappling with this challenging condition.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

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.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

Challenges in Palliative Care in Latin America: A Narrative Review.

In "graying" populations with extended lifespans and survivable forms of cancer, palliative services become increasingly important but may be difficult to introduce into public discourse, public policy, and healthcare systems. Latin America (LATAM) faces many challenges as it introduces and, in some cases, develops its palliative care programs; though the challenges faced here are in many ways universal ones, LATAM approaches may be unique and based on the region's specific culture, politics, and economics. This narrative review based on a literature search identified 10 main themes that can be interpreted as challenges and opportunities for palliative care in LATAM. These challenges are integrating palliation into healthcare systems; public policy and funding; therapeutic obstinacy; changing demographics; access to services; analgesia; the role of religion, spirituality, and folk medicine; social determinants of palliative care; low health literacy; and limited clinician training. Some of the LATAM nations have palliative programs and palliative care training in place while others are developing these systems. Integrating this care into existing healthcare and reimbursement systems has been a challenge. A notable challenge in LATAM is also access to care since palliative programs tend to cluster in metropolitan areas and create hardships for rural citizens to access them. The better-defined role of familial caregivers and telehealth may be important factors in the expansion of palliative care in LATAM and beyond.

Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.

One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.

Peripheral nerve stimulation (PNS): A valid and definitive therapeutical option for a case of anterior cutaneous nerve entrapment syndrome (ACNES).

Anterior cutaneous nerve entrapment syndrome (ACNES) is a cause of moderate to severe chronic pain, hyperesthesia/hypoesthesia, and altered perception of heat/cold in a specific region of the anterior abdominal wall, referable to the territory of innervation of one or more anterior branches of the intercostal nerves. None of the therapeutic options currently available has proved to be effective in the long term or decisive. In recent years, we have begun to treat purely sensory neuropathies, such as this, with the implantation of wireless peripheral nerve stimulators (PNS), achieving the safety of modular and personalized analgesia. We report the case of a 41-year-old man suffering from ACNES of the 8th intercostal nerve for two years. We first performed two consecutive ultrasound-guided diagnostic blocks of the anterior cutaneous branch of the 8th intercostal right nerve and then elected the patient for ultrasound-guided nerve decompression followed by neuromodulation and pulsed-radiofrequency (PRF). Taking into account full employment, young age, and the likelihood of having to repeat the treatment several times, we considered him for Peripheral Nerve Stimulation (PNS) implantation under ultrasound guidance, and we implanted the wireless lead at the anterior branch of the right 8th intercostal nerve, and programmed tonic stimulation 100 Hz PW 200 ms. The patient reported immediate pain relief and never took medication for this problem again, at two years follow-up. PNS has had an increasing role in the management of chronic neuropathic pain, especially in merely sensitive neuropathies like ACNES. We support future research on this theme.

An update on pharmacotherapy for trigeminal neuralgia.

INTRODUCTION: Trigeminal neuralgia is a rare condition that can be effectively treated by carbamazepine or oxcarbazepine but these older drugs are associated with dose-dependent and potentially treatment-limiting adverse effects. Third-generation anticonvulsants, new calcitonin gene-related peptide blockers for migraine, and older drugs such as ketamine and cannabinoids may be promising adjuvants or monotherapeutic options. AREAS COVERED: The new drugs, their presumed mechanisms of action, safety and efficacy are discussed herein. There is a paucity of robust clinical evidence in support of these drugs for trigeminal neuralgia. New migraine agents are considered as well although migraines and trigeminal neuralgia are distinct, albeit similar, conditions. No new drugs have been released to market in recent years with the specific indication of trigeminal neuralgia. EXPERT OPINION: In real-world clinical practice, about half of trigeminal neuralgia patients take more than one agent for prevention and combination therapy may be the optimal approach. Combination therapy might allow for lower doses of carbamazepine or oxcarbazepine, thus reducing the number and severity of potential adverse events but the potential for pharmacokinetic drug-drug interactions must be considered. Drug therapy for trigeminal neuralgia involves acute or abortive treatments, often administered in hospital versus long-term preventive therapy, usually involving oral agents.

Trigeminal neuralgia is a relatively rare condition that usually affects one side of the face below the eye around the cheekbone. The cause of trigeminal neuralgia is sometimes a damaged nerve or a nerve that has lost part of its outer protective sheath (myelin). However, trigeminal neuralgia may have other neurological causes as well. Pain can be triggered by touch, pressure, or chewing and it tends to occur in very painful brief attacks followed by pauses with little or no pain. There are two types of drug treatment for trigeminal neuralgia: drugs to stop an ongoing attack (which are often administered in an emergency room or hospital intravenously) and drugs that are taken orally over the long term to reduce or prevent attacks.The two most effective drugs for trigeminal neuralgia are carbamazepine and oxcarbazepine, which are actually drugs to prevent seizures. They are effective in reducing the pain intensity and number of attacks of trigeminal neuralgia but they have side effects. In fact, these side effects can be so severe that people stop taking the drugs.Many new drugs have come to market recently that may work for trigeminal neuralgia, although none was specifically developed for this use. The newest generation of anti-seizure medications including eslicarbazepine, lacosamide, levetiracetam, and retigabine, may be just as effective as the older carbamazepine and oxcarbazepine drugs with fewer side effects. Clinical studies are needed to test them in trigeminal neuralgia patients but their mechanisms of action suggest that they might work well.There are some new drugs developed for migraine headache that inhibit a substance in the body called CGRP. Migraine headaches and trigeminal neuralgia have some of the same symptoms but they are different conditions but both involve too much CGRP.Other new drugs include lasmiditan, pimozide (used for Tourette syndrome), tizanidine (muscle relaxant), lamotrigine and vixotrigine (anti-seizure drugs) may also be beneficial. It may be that people with trigeminal neuralgia will have to take combination therapy, the use of two or more drugs with different mechanisms of action. Older drugs like ketamine and cannabinoids are also being considered as possible add-on agents for therapy for trigeminal neuralgia.

Red Wine as an Aromatase Inhibitor: A Narrative Review.

As estrogen-dependent breast cancer is more affected by the local production of estrogen via aromatase than serum estrogen, aromatase inhibitors for treating breast carcinomas in postmenopausal women have been developed. As the aromatase enzyme converts endogenous androgen to estrogenic compounds, its blockade lowers the in situ production of estrogen, demonstrated to encourage tumor proliferation. Red wine, but not white wine, may have aromatase-inhibiting properties that are being elucidated, although the exact mechanisms of action are not known. Polyphenols, tannins, and resveratrol have all been implicated as aromatase blockers, and there may also be synergistic interplay among selected constituents. The role of red wine would be in chemoprevention, the use of natural or synthetic substances to retard, block, or reverse cancer. One gene encodes aromatase, so aromatase inhibition would stop endogenous estrogen production. The role of aromatase inhibition in breast cancer in premenopausal women is not clear. While animal studies have demonstrated that red wine contains constituents that could block aromatase in vivo, the benefits also exist with nonalcoholic grape seed extract. Further investigation is needed but there are challenges in designing appropriate clinical trials for a substance as variable as red wine. While there is insufficient evidence to advocate for red wine as an aromatase inhibitor, there is sufficient evidence to warrant further investigation.