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Cephalalgia : An International Journal... Feb 2022Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains a challenge to clinicians due to its poorly understood pathogenesis and... (Review)
Review
BACKGROUND
Burning mouth syndrome is a chronic idiopathic intractable intraoral dysaesthesia that remains a challenge to clinicians due to its poorly understood pathogenesis and inconsistent response to various treatments.
AIM
This review aimed to study the short- (≤3 months) and long-term (>3 months) effectiveness and sustainable benefit of different burning mouth syndrome treatment strategies and the associated side effects.
MATERIALS AND METHODS
Randomised controlled trials of burning mouth syndrome treatment compared with placebo or other interventions with a minimum follow up of 2 months were searched from the PubMed, Embase and Cochrane database (published to July 2020).
RESULTS
Twenty-two studies were selected based on the inclusion and exclusion criteria and analysed. Nine categories of burning mouth syndrome treatment were identified: Anticonvulsant and antidepressant agents, phytomedicine and alpha lipoic acid supplements, low-level laser therapy, saliva substitute, transcranial magnetic stimulation, and cognitive behaviour therapy. Cognitive behaviour therapy, topical capsaicin and clonazepam, and laser therapy demonstrated favourable outcome in both short- and long-term assessment. Phytomedicines reported a short-term benefit in pain score reduction. The pooled effect of alpha lipoic acid (ALA) pain score improvement was low, but its positive effects increased in long term assessment.
CONCLUSION
A more significant volume in terms of sample size, multi-centres, and multi-arm comparison of therapeutic agents with placebo and longitudinal follow-up studies is recommended to establish a standardised burning mouth syndrome treatment protocol. Further studies are required to assess the analgesic benefits of topical clonazepam and capsaicin, alternative medicines with neurodegenerative prevention capability and psychology support in treating burning mouth syndrome and reducing systemic adverse drug reactions. International Prospective Register of Systematic Reviews (PROSPERO):Protocol ID - CRD42020160892.
Topics: Burning Mouth Syndrome; Capsaicin; Clonazepam; Humans; Pain; Thioctic Acid
PubMed: 34404247
DOI: 10.1177/03331024211036152 -
Osteoarthritis and Cartilage Apr 2023To review the current state of pharmaceutical treatment recommendations for the management of osteoarthritis. (Review)
Review
OBJECTIVE
To review the current state of pharmaceutical treatment recommendations for the management of osteoarthritis.
METHOD
A narrative review was drafted to describe treatment guidelines, mechanism of action, pharmacokinetics, and toxicity for nine classes of pharmaceuticals: 1) oral nonsteroidal anti-inflammatory drugs (NSAIDs), 2) topical NSAIDs, 3) COX-2 inhibitors, 4) duloxetine, 5) intra-articular corticosteroids, 6) intra-articular hyaluronic acid, 7) acetaminophen (paracetamol), 8) tramadol, and 9) capsaicin.
RESULTS
In general, oral and topical NSAIDs, including COX-2 inhibitors, are strongly recommended first-line treatments for osteoarthritis due to their ability to improve pain and function but are associated with increased risks in patients with certain comorbidities (e.g., heightened cardiovascular risks). Intra-articular corticosteroid injections are generally recommended for osteoarthritis management and have relatively minor adverse effects. Other treatments, such as capsaicin, tramadol, and acetaminophen, are more controversial, and many updated guidelines offer differing recommendations.
CONCLUSION
The pharmaceutical management of osteoarthritis is a constantly evolving field. Promising treatments are emerging, and medicines that were once considered conventional (e.g., acetaminophen) are gradually becoming less acceptable based on concerns with efficacy and safety. Clinicians need to consider the latest evidence and recommendations to make an informed decision with their patients about how to optimize treatment plans for patients with knee, hip, polyarticular, or hand osteoarthritis.
Topics: Humans; Osteoarthritis, Knee; Acetaminophen; Tramadol; Capsaicin; Cyclooxygenase 2 Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Pharmaceutical Preparations
PubMed: 36414224
DOI: 10.1016/j.joca.2022.11.005 -
Molecules (Basel, Switzerland) Apr 2022Capsaicin is a natural compound found in chili peppers and is used in the diet of many countries. The important mechanism of action of capsaicin is its influence on... (Review)
Review
Capsaicin is a natural compound found in chili peppers and is used in the diet of many countries. The important mechanism of action of capsaicin is its influence on TRPV1 channels in nociceptive sensory neurons. Furthermore, the beneficial effects of capsaicin in cardiovascular and oncological disorders have been described. Many recent publications show the positive effects of capsaicin in animal models of brain disorders. In Alzheimer's disease, capsaicin reduces neurodegeneration and memory impairment. The beneficial effects of capsaicin in Parkinson's disease and depression have also been described. It has been found that capsaicin reduces the area of infarction and improves neurological outcomes in animal models of stroke. However, both proepileptic and antiepileptic effects of capsaicin in animal models of epilepsy have been proposed. These contradictory results may be caused by the fact that capsaicin influences not only TRPV1 channels but also different molecular targets such as voltage-gated sodium channels. Human studies show that capsaicin may be helpful in treating stroke complications such as dysphagia. Additionally, this compound exerts pain-relieving effects in migraine and cluster headaches. The purpose of this review is to discuss the mechanisms of the beneficial effects of capsaicin in disorders of the central nervous system.
Topics: Animals; Capsaicin; Central Nervous System; Pain; Stroke; TRPV Cation Channels
PubMed: 35458680
DOI: 10.3390/molecules27082484 -
Cells Dec 2021Capsaicin is a potent agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel and is a common component found in the fruits of the genus Capsicum... (Review)
Review
Capsaicin is a potent agonist of the Transient Receptor Potential Vanilloid type 1 (TRPV1) channel and is a common component found in the fruits of the genus Capsicum plants, which have been known to humanity and consumed in food for approximately 7000-9000 years. The fruits of Capsicum plants, such as chili pepper, have been long recognized for their high nutritional value. Additionally, capsaicin itself has been proposed to exhibit vasodilatory, antimicrobial, anti-cancer, and antinociceptive properties. However, a growing body of evidence reveals a vasoconstrictory potential of capsaicin acting via the vascular TRPV1 channel and suggests that unnecessary high consumption of capsaicin may cause severe consequences, including vasospasm and myocardial infarction in people with underlying inflammatory conditions. This review focuses on vascular TRPV1 channels that are endogenously expressed in both vascular smooth muscle and endothelial cells and emphasizes the role of inflammation in sensitizing the TRPV1 channel to capsaicin activation. Tilting the balance between the beneficial vasodilatory action of capsaicin and its unwanted vasoconstrictive effects may precipitate adverse outcomes such as vasospasm and myocardial infarction, especially in the presence of proinflammatory mediators.
Topics: Animals; Blood Vessels; Capsaicin; Cardiovascular System; Humans; Inflammation; TRPV Cation Channels; Vasodilation
PubMed: 35011580
DOI: 10.3390/cells11010018 -
Molecular Nutrition & Food Research Dec 2022Spicy foods and chili peppers contain the primary ingredient capsaicin, which has potential health benefits. However, their efficacy in some health outcomes is also... (Review)
Review
Spicy foods and chili peppers contain the primary ingredient capsaicin, which has potential health benefits. However, their efficacy in some health outcomes is also fiercely disputed, and some side effects have been confirmed. To assess the quality and strength of the associations between spicy food and chili pepper consumption and different health outcomes. An umbrella review is performed in humans. Eleven systematic reviews and meta-analyses with a total of 27 findings are identified. The health effect of consuming spicy food and chili peppers is unclear. Furthermore, the characteristics and context of different world regions and populations should be carefully considered. Direct correlations exist in esophageal cancer, gastric cancer, and gallbladder cancer. However, negative connections are reported in metabolism, mortality, and cardiovascular disease. Dose-response analysis reveals a significant nonlinear relationship between gastric cancer risk and capsaicin intake. The consumption of spicy foods and chili peppers is typically safe. However, high-quality proof is available to confirm this conclusion.
Topics: Humans; Capsicum; Capsaicin; Stomach Neoplasms; Cardiovascular Diseases
PubMed: 36111960
DOI: 10.1002/mnfr.202200167 -
Pharmacology & Therapeutics Apr 2021Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1... (Review)
Review
Capsaicin, the pungent ingredient in chili peppers, produces intense burning pain in humans. Capsaicin selectively activates the transient receptor potential vanilloid 1 (TRPV1), which is enriched in nociceptive primary afferents, and underpins the mechanism for capsaicin-induced burning pain. Paradoxically, capsaicin has long been used as an analgesic. The development of topical patches and injectable formulations containing capsaicin has led to application in clinical settings to treat chronic pain conditions, such as neuropathic pain and the potential to treat osteoarthritis. More detailed determination of the neurobiological mechanisms of capsaicin-induced analgesia should provide the logical rationale for capsaicin therapy and help to overcome the treatment's limitations, which include individual differences in treatment outcome and procedural discomfort. Low concentrations of capsaicin induce short-term defunctionalization of nociceptor terminals. This phenomenon is reversible within hours and, hence, likely does not account for the clinical benefit. By contrast, high concentrations of capsaicin lead to long-term defunctionalization mediated by the ablation of TRPV1-expressing afferent terminals, resulting in long-lasting analgesia persisting for several months. Recent studies have shown that capsaicin-induced Ca/calpain-mediated ablation of axonal terminals is necessary to produce long-lasting analgesia in a mouse model of neuropathic pain. In combination with calpain, axonal mitochondrial dysfunction and microtubule disorganization may also contribute to the longer-term effects of capsaicin. The analgesic effects subside over time in association with the regeneration of the ablated afferent terminals. Further determination of the neurobiological mechanisms of capsaicin-induced analgesia should lead to more efficacious non-opioidergic analgesic options with fewer adverse side effects.
Topics: Analgesia; Analgesics; Animals; Calpain; Capsaicin; Chronic Pain; Mice; Neuralgia; TRPV Cation Channels
PubMed: 33181192
DOI: 10.1016/j.pharmthera.2020.107743 -
Diabetes & Metabolism Journal Nov 2023Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of... (Review)
Review
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.
Topics: United States; Humans; Diabetic Neuropathies; Capsaicin; Quality of Life; Duloxetine Hydrochloride; Neuralgia; Diabetes Mellitus
PubMed: 37670573
DOI: 10.4093/dmj.2023.0018 -
Cell Chemical Biology Aug 2022Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses...
Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.
Topics: Capsaicin; Carrier Proteins; Cyclooxygenase 2; Humans; Inflammation; L-Lactate Dehydrogenase; Lipopolysaccharides; Membrane Proteins; Sepsis; TRPV Cation Channels; Thyroid Hormones; Thyroid Hormone-Binding Proteins
PubMed: 35858615
DOI: 10.1016/j.chembiol.2022.06.011 -
Journal of Cachexia, Sarcopenia and... Feb 2023Cisplatin (CP) is a widely used chemotherapeutic drug with subsequent adverse effects on different organs and tissues including skeletal muscle loss and atrophy as the...
BACKGROUND
Cisplatin (CP) is a widely used chemotherapeutic drug with subsequent adverse effects on different organs and tissues including skeletal muscle loss and atrophy as the most common clinical symptoms. The molecular mechanism of cisplatin-induced muscle atrophy is not clearly understood. However, recent significant advances indicate that it is related to an imbalance in both the protein status and apoptosis. Capsaicin (CAP) is one of the major ingredients in chilli peppers. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation with particular therapeutic potential in muscle atrophy. However, the mechanisms underlying its protective effects against cisplatin-induced muscle loss and atrophy remain largely unknown. This study aims to investigate capsaicin's beneficial effects on cisplatin-induced muscle loss and atrophy in vitro and in vivo.
METHODS
The anti-muscle-atrophic effect of capsaicin on cisplatin-induced muscle loss was investigated using in vivo and in vitro studies. By using the pretreatment model, pretreated capsaicin for 24 h and treated with cisplatin for 48 h, we utilized a C C myotube formation model where cell viability analysis, immunofluorescence, and protein expression were measured to investigate the effect of capsaicin in hampering cisplatin-induced muscle atrophy. C57BL/6 mice were administered capsaicin (10, 40 mg/kg BW) as a pretreatment for 5 weeks and cisplatin (3 mg/kg BW) for seven consecutively days to assess muscle atrophy in an animal model for protein and oxidative stress examination, and the grip strength was tested to evaluate the muscle strength.
RESULTS
Our study results indicated that cisplatin caused lower cell viability and showed a subset of hallmark signs typically recognized during atrophy, including severe reduction in the myotube diameter, repression of Akt, and mTOR protein expression. However, pretreatment with capsaicin could ameliorate cisplatin-induced muscle atrophy by up-regulating the protein synthesis in skeletal muscle as well as down-regulating the markers of protein degradation. Additionally, capsaicin was able to downregulate the protein expression of apoptosis-related markers, activated TRPV1 and autophagy progress modulation and the recovery of lysosome function. In vivo, capsaicin could relieve oxidative stress and cytokine secretion while modulating autophagy-related lysosome fusion, improving grip strength, and alleviating cisplatin-induced body weight loss and gastrocnemius atrophy.
CONCLUSIONS
These findings suggest that capsaicin can restore cisplatin-induced imbalance between protein synthesis and protein degradation pathways and it may have protective effects against cisplatin-induced muscle atrophy.
Topics: Animals; Mice; Capsaicin; Cisplatin; Mice, Inbred C57BL; Muscle, Skeletal; Muscular Atrophy
PubMed: 36401337
DOI: 10.1002/jcsm.13120 -
Redox Biology Oct 2022Oxidative stress and the resultant hyperpermeability play a vital role in the pathogenesis of diabetic retinopathy (DR). Poldip2 has been implicated in HO production,...
BACKGROUND
Oxidative stress and the resultant hyperpermeability play a vital role in the pathogenesis of diabetic retinopathy (DR). Poldip2 has been implicated in HO production, but the effects of capsaicin on poldip2 have not been reported.
METHODS
Diabetic Sprague-Dawley (SD) rats induced with STZ were treated with capsaicin or AAV-poldip2-shRNA, and human retinal microvascular endothelial cells (HRMECs) were treated with capsaicin or poldip2 siRNA.
RESULTS
Current data indicated that the expression of PPARγ, poldip2, Nox4, VCAM-1, HIF-1α, and VEGF increased in rat retinas with DR and in HRMECs treated with high glucose. The production of ROS or HO in the tissues, serum, and cells increased, and the paracellular permeability of cultured HRMECs with high glucose significantly increased. In addition, overt hyperpermeability of retinal microvessels and increased retinal neovascularization in diabetic rats were observed. However, capsaicin treatment inhibited these increases and suppressed the expression of PPARγ by enhancing its phosphorylation and ubiquitination in the retinas of DR rats. Poldip2 knockdown in HRMECs or its silencing in the retina of DR rats concomitantly led to reduced levels of Nox4, VCAM-1, HIF-1α, VEGF, ROS, and HO, and the paracellular permeability of HRMECs or the hyperpermeability of retinal microvessels in diabetic rat retinas decreased. Similarly, after PPARγ knockdown in HRMECs, poldip2, Nox4, HIF-1α, VEGF, ROS, and HO decreased, and the monolayer paracellular permeability was reduced accordingly.
CONCLUSION
Capsaicin may ameliorate diabetic retinopathy by activating TRPV1 and suppressing the PPARγ-poldip2-Nox4 pathway.
Topics: Animals; Capsaicin; Carrier Proteins; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelial Cells; Glucose; Humans; Hydrogen Peroxide; Nuclear Proteins; Oxidative Stress; PPAR gamma; RNA, Small Interfering; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Retina; Vascular Cell Adhesion Molecule-1; Vascular Endothelial Growth Factor A
PubMed: 36088760
DOI: 10.1016/j.redox.2022.102460