curcumin and Pain

Conflicting evidence exists concerning the effects of nutrient intake in osteoarthritis (OA). A systematic literature review and meta-analysis were performed using PubMed, EMBASE, and Cochrane Library up to November 2021 to assess the effects of nutrients on pain, stiffness, function, quality of life, and inflammation markers. We obtained 52 references including 50 on knee OA. Twelve studies compared 724 curcumin patients and 714 controls. Using the standardized mean difference, improvement was significant with regard to pain and function in the curcumin group compared to placebo, but not with active treatment (i.e., nonsteroidal anti-inflammatory drugs, chondroitin, or paracetamol). Three studies assessed the effects of ginger on OA symptoms in 166 patients compared to 164 placebo controls. Pain was the only clinical parameter that significantly decreased. Vitamin D supplementation caused a significant decrease in pain and function. Omega-3 and vitamin E caused no changes in OA parameters. Herbal formulations effects were significant only for stiffness compared to placebo, but not with active treatment. A significant decrease in inflammatory markers was found, especially with ginger. Thus, curcumin and ginger supplementation can have a favorable impact on knee OA symptoms. Other studies are needed to better assess the effects of omega-3 and vitamin D.

Topics: Curcumin; Dietary Supplements; Humans; Osteoarthritis, Knee; Pain; Quality of Life; Vitamin D; Zingiber officinale

The aim was to systematically review randomized controlled trials (RCTs) that assessed the effectiveness of curcumin in reducing self-rated pain levels in the orofacial region (OFR). The addressed focused question was "Is curcumin effective in reducing self-rated pain levels in the OFR?". Indexed databases (PubMed (National Library of Medicine), Scopus, EMBASE, MEDLINE (OVID), and Web of Science) were searched up to and including February 2022 using different keywords. The inclusion criteria were (a) original studies (RCTs) in indexed databases; and (b) studies assessing the role of curcumin in the management of pain in the OFR. The risk of bias was assessed using the Cochrane risk of bias tool. The pattern of the present systematic review was customized to primarily summarize the pertinent information. Nineteen RCTs were included. Results from 79% of the studies reported that curcumin exhibits analgesic properties and is effective in reducing self-rated pain associated with the OFR. Three studies had a low risk of bias, while nine and seven studies had a moderate and high risk of bias, respectively. Curcumin can be used as an alternative to conventional therapies in alleviating pain in the OFR. However, due to the limitations and risk of bias in the aforementioned studies, more high-quality RCTs are needed.

Topics: Curcumin; Humans; Pain; Randomized Controlled Trials as Topic

Recurrent aphthous stomatitis (RAS) is the most common ulcerative lesion of the oral mucosa. The management of RAS is quite challenging with no definitive cure.. The present systematic review aimed to summarize the available evidence regarding the efficacy of curcumin in the management of RAS.. PubMed, Scopus and Web of Science databases were searched in June 2020 for all relevant studies. Clinical trials that assessed the efficacy of curcumin for the management of RAS were included. The primary outcomes were pain and/or clinical improvement.. Eight studies involving 439 subjects were included. The efficacy of curcumin was compared with 1% triamcinolone in four studies, glycerin vehicle in one study, placebo in one study, and honey in one study. Overall, the included studies reported a good efficacy of curcumin in reducing pain and ulcers size in patients with RAS. Four studies found curcumin as effective as triamcinolone in relieving signs and symptoms of RAS. Three studies reported superior results with curcumin as compared with control groups.. The limited available evidence suggests that curcumin have potential benefits in alleviating pain and accelerating healing in patients with RAS. Further well-designed clinical trials with standardized curcumin formulations are highly recommended.

Topics: Curcumin; Humans; Pain; Stomatitis, Aphthous; Triamcinolone

Pain is an unpleasant sensation that has complex and varying causative etiology. Modern drug discovery focuses on identifying potential molecules that target multiple pathways with a safer profile compared to those with a single target. The current treatment of pain and inflammation with the available therapeutics has a number of major side effects. Pain is one of the major clinical problems that need functional therapeutics which act on multiple targets and with low toxicity. Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has been used for years in Ayurvedic, Chinese, and in many other systems of traditional medicine. Pre-clinical data published thus far demonstrated that curcumin possesses multi-target biological functions, suggesting its potential use to cure different diseases. However, there is no or very brief systematic review of its potential use in pain and inflammation with underlying mechanisms for such activities. Accordingly, the aim of the current review was to update the pre-clinical data of curcumin and its multiple targeting pathways for analgesic and anti-inflammatory effects, and to further propose a molecular mechanism(s). A literature study was conducted using different known databases, including Pubmed, SciFinder, Google Scholar, and Science Direct. Available pre-clinical data suggest the ameliorating effect of curcumin in pain and inflammation is rendered through the modulation of pain pathways, including inhibition of a number of pro-inflammatory mediators, inhibition of oxidative stress and cyclooxygenase-2 (COX-2), down-regulation of Ca2+/calmodulin-depend protein kinase II (CaMKIIα) and calcium channels like transient receptor potential (TRP), modulation of metabotropic glutamate receptor-2 (mGlu2), modulation of monoamine system, inhibition of JAK2/STAT3 signaling pathway, remodeling of extracellular matrix proteins, inhibition of apoptosis, inhibition of JNK/MAPK and ERK/CREB signaling pathway, and activation of the opioid system. Taken all together, it is evident that curcumin is one of the promising, safe, and natural polyphenolic molecules that target multiple molecular pathways in pain and can be beneficial in the treatment and management of pain and inflammation.

Topics: Apoptosis; Curcumin; Humans; Inflammation; Pain; Signal Transduction

Turmeric (Curcuma longa) and its constituent, curcumin, have been used for their therapeutic properties for a long time. Most of the medicinal impacts of turmeric and curcumin might be attributed to their anti-inflammatory, antinociceptive, and antioxidant effects. In the present review, the preventive and therapeutic potentials of turmeric and its active constituent, curcumin, on inflammatory disorders and pain as well as patents related to their analgesic and anti-inflammatory effects, have been summarized to highlight their value on human health. A literature review was accomplished in Google Scholar, PubMed, Scopus, Google Patent, Patentscope, and US Patent. Several documents and patents disclosed the significance of turmeric and curcumin to apply in several therapeutic, medicinal, and pharmaceutical fields. These phytocompounds could be applied as a supplementary therapy in phytotherapy, inflammatory disorders such as arthritis, inflammatory bowel diseases, osteoarthritis, psoriasis, dermatitis, and different types of pain including neuropathic pain. However, because of inadequate clinical trials, further high-quality studies are needed to firmly establish the clinical efficacy of the plant. Consistent with the human tendency to the usage of phytocompounds rather than synthetic drugs, particular consideration must be dedicated to bond the worth of turmeric and curcumin from basic sciences to clinical applications.

Topics: Anti-Inflammatory Agents; Curcuma; Curcumin; Humans; Pain; Phytotherapy

Recurrent aphthous stomatitis (RAS) lesions are inflammatory painful oral ulcers with uncertain etiology. Curcumin acts as an effective anti-inflammatory and antibacterial agent in the treatment of various oral diseases. This systematic review aimed to assess the effects of curcumin on RAS. A systematic search of the medical databases, PubMed, Scopus, ISI, Science Direct, and Google Scholar was performed up to March 30, 2020, to identify clinical trials assessing the effect of curcumin on aphthous ulcers. Nine studies comprising of 469 participants met all criteria and were analyzed. Treatment with curcumin significantly reduced aphthous ulcer size (seven studies), pain intensity (eight studies), number of aphthous ulcers (three studies), erythematous halo (one study), and erythema and exudate of the aphthous (one study). In four studies, the effect of curcumin on aphthous ulcer was assessed in comparison to the effects of the standard medication, triamcinolone. In all of these studies, curcumin had similar beneficial effects on the aphthous ulcer as measured by ulcer size, number, and pain. Only three studies were categorized as high quality using the Jadad scale. Within the limitations of this review, it can be concluded that curcumin may have a beneficial role in the treatment of recurrent aphthous ulcers. However, more randomized clinical trials are needed to validate these findings.

Topics: Anti-Inflammatory Agents; Curcumin; Humans; Pain; Recurrence; Stomatitis, Aphthous

Osteoarthritis is characterized by degeneration of joint structure over time, resulting in limitation of joint mobility. There is growing evidence that curcumin has anti-inflammatory properties and could be a potential therapeutic option for chronic inflammatory diseases. Hence, curcumin could potentially have a positive impact on osteoarthritis symptoms. This systematic review aimed to estimate the effects of curcumin on osteoarthritis. We systematically searched PubMed, ISI, Scopus, and Google Scholar up to March 4, 2020 to identify randomized controlled trials that evaluated the effects of consumption of all types of curcumin compounds in the treatment of osteoarthritis, especially in patients with knee osteoarthritis. Seventeen trials were identified. The duration of the included studies varied from 4 weeks to 8 months. Across all trials, 13 studies involved screening using Western Ontario and McMaster Universities (WOMAC) scores and 11 studies used visual analog scales (VAS) for recording pain from baseline to post-intervention. There was a significant improvement in VAS and overall WOMAC scores with oral administration of various types of curcumin formulations with no severe adverse effects. In conclusion, different types of curcumin compounds may be beneficial as an alternative or complementary agent for the management of osteoarthritis. Moreover, certain curcumin compounds with higher bioavailability tended to show more positive effects.

Topics: Curcumin; Humans; Osteoarthritis, Knee; Pain; Pain Measurement; Treatment Outcome; Visual Analog Scale

Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA.. Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcuma; Humans; Osteoarthritis, Knee; Pain; Plant Extracts; Randomized Controlled Trials as Topic

Current analgesic pharmacotherapy-opioids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen (paracetamol) and related drugs-is effective for acute pain, but their use is limited by adverse effects on the renal, hepatic, cardiovascular or gastrointestinal systems, or they have potential for abuse. Therefore, alternative options are desired. Compounds used in traditional medicine might offer such alternatives, but the evidence must be based on pharmacologic properties and on clinical trial data. This review summarizes the evidence for one of these: the analgesic properties of turmeric and other curcumins.. The PubMed database and other sources were searched using keywords related to turmeric, curcumin, antinociception and analgesia. Primary sources and reviews of preclinical and clinical studies were identified, assessed and summarized. Bibliographies within these sources provided additional information.. Turmeric has consistently been demonstrated to produce analgesic and anti-inflammatory effects in animal models and in clinical trials, and appears to have less serious adverse effects than many current analgesics.. Turmeric (curcumin) appears to be a possible candidate for consideration for use as a stand-alone analgesic, or in analgesic combinations as part of opioid-, NSAID- or paracetamol (acetaminophen)-sparing strategies.

Topics: Analgesia; Analgesics; Animals; Anti-Inflammatory Agents; Curcuma; Curcumin; Humans; Pain

Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is a major clinical problem that is poorly treated with available therapeutics. Curcumin is a phenolic compound derived from Curcuma longa, being widely used for its antioxidant, anti-inflammatory and immunomodulatory effects.. This review systematically summarized updated information on the traditional uses of curcumin in order to explore antinociceptive effects in pathological pain and evaluate future therapeutic opportunities clinically. Moreover, some structure-activity relationships would greatly enrich the opportunity of finding new and promising lead compounds and promote the reasonable development of curcumin.. PubMed were searched and the literature from the year 1976 to January 2018 was retrieved using keywords pain and curcumin.. This review systematically summarized updated information on the traditional uses, chemical constituents and bioactivities of curcumin, and highlights the recent development of the mechanisms of curcumin in the pathological pain by sciatic nerve injury, spinal cord injury, diabetic neuropathy, alcoholic neuropathy, chemotherapy induced peripheral neuroinflammtion, complete Freund's adjuvant (CFA) injection or carrageenan injection. Importantly, the clinical studies provide a compelling justification for its use as a dietary adjunct for pain relief. And we also present multiple approaches to improve bioavailability of curcumin for the treatment of pathological pain.. This review focuses on pre-clinical and clinical studies in the treatment of pathological pain. Although the mechanisms of pain mitigating effects are not very clear, there is compelling evidence proved that curcumin plays an essential role. However, further high-quality clinical studies should be undertaken to establish the clinical effectiveness of curcumin in patients suffering from pathological pain. Potential methods of increase the water solubility and bioavailability of curcumin still need to be studied. These approaches will help in establishing it as remedy for pathological pain.

Topics: Analgesics; Animals; Curcumin; Humans; Pain; Pain Measurement

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P < .00001), whereas meta-analysis of four studies showed a decrease of WOMAC with turmeric/curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

Topics: Arthritis, Rheumatoid; Curcuma; Curcumin; Humans; Osteoarthritis; Pain; Phytotherapy; Plant Extracts; Treatment Outcome

Cancer is primarily a disease of old age, and that life style plays a major role in the development of most cancers is now well recognized. While plant-based formulations have been used to treat cancer for centuries, current treatments usually involve poisonous mustard gas, chemotherapy, radiation, and targeted therapies. While traditional plant-derived medicines are safe, what are the active principles in them and how do they mediate their effects against cancer is perhaps best illustrated by curcumin, a derivative of turmeric used for centuries to treat a wide variety of inflammatory conditions. Curcumin is a diferuloylmethane derived from the Indian spice, turmeric (popularly called "curry powder") that has been shown to interfere with multiple cell signaling pathways, including cell cycle (cyclin D1 and cyclin E), apoptosis (activation of caspases and down-regulation of antiapoptotic gene products), proliferation (HER-2, EGFR, and AP-1), survival (PI3K/AKT pathway), invasion (MMP-9 and adhesion molecules), angiogenesis (VEGF), metastasis (CXCR-4) and inflammation (NF-kappaB, TNF, IL-6, IL-1, COX-2, and 5-LOX). The activity of curcumin reported against leukemia and lymphoma, gastrointestinal cancers, genitourinary cancers, breast cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, melanoma, neurological cancers, and sarcoma reflects its ability to affect multiple targets. Thus an "old-age" disease such as cancer requires an "age-old" treatment.

Topics: Antineoplastic Agents; Curcumin; Drug Delivery Systems; Humans; Neoplasms; Pain; Plant Extracts; Signal Transduction

Carpal Tunnel Syndrome (CTS) is provoked by the compression of the median nerve, leading to nerve ischemia, endoneural edema, venous congestion, and subsequent metabolic alterations. Conservative treatments could be considered. The present study investigates the efficacy of a specific blend of a 600 mg dietary integrator composed of acetyl-L-carnitine, α-lipoic acid, phosphatidylserine, Curcumin, C, E and B1, B2, B6 and B12 vitamins in patients with mild to moderate CTS.. The present investigation involved the outpatients who were planned to undergo open surgical decompression of the median nerve awaiting surgery from June 2020 and February 2021. CTS surgery has been significantly reduced in our institutions during the COVID-19 pandemic. Patients were randomized into Group A (dietary integration 600 mg twice day for 60 days) and Group B (control group, no drug administration). Clinical and functional improvement was prospectively measured after 60 days Results: One-hundred forty-seven patients completed the study, 69 from group A and 78 from group B. BCTQ was significantly improved with the drug administration, as well as BCTQ symptoms subscale, and the pain. BCTQ function subscale and Michigan Hand Questionnaire was not significantly improved. Ten patients in group A (14.5%) declared that they didn't need further treatment. No major side effects were noticed.. Dietary integration could be considered as an option in patients who could not undergo surgery. Symptoms and pain could improve, but surgery remains the gold standard for recovery of function in mild to moderate CTS.

Topics: Acetylcarnitine; Carpal Tunnel Syndrome; COVID-19; Curcumin; Humans; Pain; Pandemics; Phosphatidylserines; Prospective Studies; Thioctic Acid; Treatment Outcome; Vitamin B Complex

To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia.. Randomised, double blind controlled trial, with central randomisation.. Thai traditional medicine hospital, district hospital, and university hospitals in Thailand.. Participants with a diagnosis of functional dyspepsia.. The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days.. Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events.. 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred.. Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect.. TCTR20221208003.

Topics: Adult; Curcumin; Dyspepsia; Female; Humans; Middle Aged; Omeprazole; Pain; Proton Pump Inhibitors

Functional dyspepsia (FD) is a common problem in gastroenterology practice. The study aimed to compare the efficacy of Curcuma longa Linn versus omeprazole and placebo among patients diagnosed with FD.. From November 2017 to November 2018, patients diagnosed with FD according to ROME IV criteria were enrolled. Patients were randomized into curcumin, omeprazole, or placebo groups. The Severity of Dyspepsia Assessment (SODA) was used to evaluate clinical effectiveness after 2 and 4 weeks. Health-related quality of life was assessed using the EuroQol-5 Dimension questionnaire.. A total of 132 patients were randomized. Forty-five, 43, and 44 patients were in the curcumin, omeprazole, and placebo groups, respectively. At 4 weeks, the mean SODA score change of pain and non-pain symptoms decreased in the curcumin group compared with the placebo group (pain -16.98 ± 8.09 vs -10.53 ± 4.43; P < 0.001, non-pain -7.96 ± 3.41 vs -6.05 ± 3.03; P < 0.008). No significant difference was observed between curcumin and omeprazole groups (pain -16.98 ± 8.09 vs -14.69 ± 6.41; P = 0.302, non-pain -7.96 ± 3.41 vs -7.07 ± 2.27; P = 0.486). The mean change of the SODA satisfaction score at 4 weeks was higher in the curcumin group compared with the omeprazole group but without statistical significance (9.17 ± 3.88 vs 8.63 ± 3.89, P = 1). The mean change of EQ-5D index at 4 weeks was highest in the curcumin group but not statistically different from other groups (0.12 ± 0.13 vs 0.09 ± 0.10 vs 0.07 ± 0.05; P = 0.055).. Curcuma longa Linn can improve dyspeptic symptoms, improve quality of life, and provide satisfaction equivalent to omeprazole in treatment of FD.

Topics: Curcuma; Curcumin; Double-Blind Method; Dyspepsia; Humans; Omeprazole; Pain; Quality of Life; Treatment Outcome

This study aimed to assess the efficacy of a novel curcumin formulation, HydroCurc®, for alleviating joint pain and improving quality of life in adults.. A randomised, double blind, placebo-controlled study was conducted on adults aged 25-70 years reporting joint pain. Eighty participants received either curcumin or a placebo daily for 2 weeks. The primary outcome was a self-assessed reduction in pain as assessed by a visual analogue scale (VAS) for pain, completed daily in the morning and evening. Quality of life was assessed by the RAND 36-Item Health Survey (SF-36) and the Profile of Mood States (POMS).. VAS pain scores reduced over the 2 weeks of treatment in both groups. Morning VAS scores were significantly reduced from baseline in the curcumin and placebo groups from day 6 and 12, respectively. Morning VAS scores were significantly lower in the curcumin group compared to the placebo group for days 11, 13, and 14 (p < 0.05). Evening VAS scores were significantly reduced from baseline in the curcumin and placebo groups from day 5 and 6, respectively. There were no differences in the evening VAS scores, SF-36 nor POMS between groups.. This study demonstrates that HydroCurc® is an effective option for reducing morning joint pain. Future studies would benefit from investigating whether long-term supplementation and/or a split dose can show further improvements in pain scores.. Einleitung: Mit dieser Studie sollte die Wirksamkeit der neuartigen Curcumin-Formulierung HydroCurc® zur Linderung von Gelenkschmerzen und zur Erhöhung der Le­bensqualität bei Erwachsenen untersucht werden. Me­thode: Es handelte sich um eine randomisierte, placebokontrollierte Doppelblindstudie mit Erwachsenen im Alter von 25 bis 70 Jahren, die über Gelenkschmerzen berichteten. Achtzig (80) Teilnehmer erhielten 2 Wochen lang täglich entweder Curcumin oder ein Placebo. Primäres Zielkriterium war eine Selbsteinschätzung der Schmerzlinderung anhand einer visuellen Analogskala (VAS) für Schmerzen, die täglich morgens und abends ausgefüllt wurde. Die Bewertung der Lebensqualität erfolgte mithilfe des RAND Short Form (36) Gesundheitsfragebogens (SF-36) und des Profile of Mood States (POMS). Ergebnisse: Die VAS-Schmerzscores nahmen im Verlauf der zwei Behandlungswochen in beiden Gruppen ab. Die morgendlichen VAS-Scores waren in der Curcumin- und in der Placebogruppe ab Tag 6 bzw. Tag 12 im Vergleich zum Ausgangswert signifikant verringert. In der Curcumin-Gruppe fielen die morgendlichen VAS-Scores an Tag 11, 13 und 14 signifikant niedriger aus als in der Placebo-Gruppe (p < 0,05). Die abendlichen VAS-Scores waren in der Curcumin- und in der Placebogruppe ab Tag 5 bzw. ab Tag 6 im Vergleich zum Ausgangswert signifikant verringert. Bei den abendlichen VAS-Scores, den SF-36- und den POMS-Werten fanden sich keine Unterschiede zwischen den Gruppen. Schlussfolgerung: Diese Studie zeigt, dass HydroCurc® eine wirksame Option zur Verringerung morgendlicher Gelenkschmerzen darstellt. Ob sich durch eine Langzeit-Supplementierung und/oder eine Teilung der Dosis weitere Verbesserungen der Schmerz-Scores erreichen lassen, sollte in zukünftigen Studien untersucht werden.

Topics: Adult; Arthralgia; Curcumin; Double-Blind Method; Humans; Pain; Quality of Life

Recurrent aphthous stomatitis (RAS) is a highly prevalent painful inflammatory condition. Curcumin is currently used as a medicinal herb with optimal anti-inflammatory properties for many inflammatory conditions. However, due to its low water solubility and consequently low bioavailability, its nanoparticulate formulation has been considered for use. This study aimed to compare the efficacy of topical application of 1% curcumin nanomicelle gel and 2% curcumin gel for treatment of RAS.. This double-blind randomized clinical trial evaluated 48 RAS patients. The patients randomly received 1% curcumin nanomicelle gel or 2% curcumin gel, and were asked to apply it 3 times/day for 1 week. The severity of pain was measured using a visual analog scale (VAS), and the size of lesions (in millimeters) was measured by a periodontal probe before (baseline), and at 4, and 7 days after treatment. Data were analyzed by repeated measures ANOVA.. No significant difference was noted in the pain score (P = .160) or size of lesions (P = .432) between the 2 groups at baseline. At 7 days, the pain score and size of lesions significantly decreased in both groups (P < .05). The reduction in pain score and lesion size was significantly greater in the curcumin nanomicelle gel group at both 4 and 7 days (P < .05). Also, the efficacy index (EI) was higher in curcumin nanomicelle gel group.. The 1% curcumin nanomicelle gel can be effectively used to enhance the healing of RAS.

Topics: Curcumin; Cyclooxygenase Inhibitors; Double-Blind Method; Humans; Pain; Stomatitis, Aphthous

Despite advances in medical technology, radiation-induced dermatitis occurs in 95% of cancer patients receiving radiation therapy. Currently, there is no standard and effective treatment for the prevention or control of radiation dermatitis. The aim of this study was to determine the efficacy of nano-curcumin in alleviating the radiation-induced skin reactions (RISRs) in breast cancer patients.. A randomized, triple-blinded, placebo-controlled clinical trial was performed on 42 patients with breast cancer. The patients were randomly allocated to receive radiotherapy plus placebo (control group) and radiotherapy plus 80 mg/day nano-curcumin capsules (treatment group) up to two weeks after the end of treatment. Then, the RISRs (graded by the radiation therapy oncology group (RTOG) scale) and pain level of the patients were evaluated at baseline and weekly. Finally, the results were analyzed by T-test and Pearson chi-square test.. According to the RTOG scale, 0%, 14.28%, and 85.71% of patients in the control group showed grades 0, 1, and 2 RISRs, respectively. In the treatment group, it was observed that 9.52%, 47.61%, and 42.85% of patients had grades 0, 1, and 2 RISRs, respectively. Compared to the control group, it was found that concomitant use of the nano-curcumin supplement did not significantly reduce the RISR severity during the first to sixth weeks (P > 0.05); however, there was a significant difference at week 7 (P = 0.01). Moreover, the patient-reported pain, as the secondary endpoint, was significantly reduced in the treatment group compared with the control group (P < 0.05).. In general, it was found that the administration of nano-curcumin could alleviate radiation- induced skin toxicity of breast cancer patients, but this effect was not significant.

Topics: Breast Neoplasms; Curcumin; Double-Blind Method; Female; Humans; Pain; Radiodermatitis; Radiopharmaceuticals

This study aimed to assess the synergistic effects of curcumin with and without strengthening exercises in rheumatoid arthritis (RA). Randomised controlled trial study was conducted from May 2021 to December 2021. Ninety patients were randomised into two groups. Group A was treated with strengthening exercises and curcumin. Group B was given curcumin only. Curcumin dosed at 180 mg/day was given orally to both groups. The treatment regimen was distributed as 3 sessions/week; each session lasted 45 minutes for group A. Serological findings and X-rays of the joints were also done for assessment. Pain, morning stiffness, and functional activities were assessed using the WOMAC and NPRS scale at baseline, 12th week, and 24th week. There was higher significant (p<0.000) reduction in quantitative values of RF, ESR and CRP, WOMAC pain, ADLs, and stiffness readings in group A. This study will project to a screening of newer and more effective interventions to treat RA. Key Words: Curcumin, Rheumatoid arthritis, Strengthening exercises.

Topics: Activities of Daily Living; Arthritis, Rheumatoid; Curcumin; Exercise; Humans; Pain

Oral mucositis is the most common toxicity of chemoradiotherapy treatment of head and neck cancers. The present study was performed to evaluate the effect of a researched turmeric formulation on oral mucositis in patients receiving chemoradiotherapy for oral cancer.. This randomized double-blinded placebo-controlled trial included 60 patients with oral cancer who had undergone radical surgery. Patients were equally randomized into 3 arms. Bio-enhanced turmeric formulation (BTF) capsules (low dose [1 g/day] or high dose [1.5 g/day]) or placebo was administered daily for 6 weeks with concurrent chemoradiotherapy. Study endpoints included the impact of the treatment on chemoradiotherapy-induced oral mucositis along with dysphagia, oral pain, dermatitis, and weight loss.. The incidence of grade 3 toxicity of oral mucositis, oral pain, dysphagia, and dermatitis was significantly lower in patients who received BTF than placebo. Twenty-five and 20% patients in BTF 1 g/day (p = 0.011) and 1.5 g/day (p = 0.004) arms, respectively, developed grade 3 oral mucositis compared to 65% patients in the placebo arm. Thirty-five and 30% patients in BTF 1 g/day (p = 0.027) and 1.5 g/day (p = 0.011) arms, respectively, developed grade 3 oral pain compared to 70% patients in the placebo arm. Twenty-five and 20% patients in BTF 1 g/day (p = 0.025) and 1.5 g/day (p = 0.010) arms, respectively, developed grade 3 dysphagia compared to 60% patients in the placebo arm. Ten and 5% patients in BTF 1 g/day (p = 0.114) and 1.5 g/day (p = 0.037) arms. respectively, developed grade 3 dermatitis compared to 30% patients in the placebo arm. Patients under BTF supplementation experienced significantly less weight loss and greater compliance with treatment than placebo.. BTF (BCM-95®) can significantly reduce chemoradiotherapy-induced severe oral mucositis, dysphagia, oral pain, and dermatitis in oral cancer patients.. Clinical Trials Registry, India (Registration No. CTRI) (CTRI/2015/12/006413 dated December 4, 2015).

Topics: Chemoradiotherapy; Curcuma; Deglutition Disorders; Dermatitis; Double-Blind Method; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Pain; Stomatitis; Weight Loss

Curcumin, a phytochemical from the spice turmeric, has anti-inflammatory properties and has been shown to have pain-relieving effects. In this 8-week, randomised, double-blind, placebo-controlled study, 101 adults with knee osteoarthritis received either 500 mg twice daily of a standardised curcumin extract (Curcugen

Topics: Aged; Anti-Inflammatory Agents; Curcuma; Curcumin; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Plant Extracts; Treatment Outcome; Walk Test

Turmeric extracts (TEs) have been shown to be suitable as a pain treatment for human joint arthritis. In a pilot, randomized clinical trial, 68 individuals with mild/moderate knee joint pain (KJP) consumed a new formulation of water-soluble TEs and insoluble curcuminoids (B-Turmactive

Topics: Arthralgia; Curcuma; Double-Blind Method; Humans; Knee Joint; Osteoarthritis, Knee; Pain; Plant Extracts; Treatment Outcome

LI73014F2 is a novel composition prepared from extracts of Terminalia chebula fruit, Curcuma longa rhizome, and Boswellia serrata gum resin with synergistic benefit in 5-Lipoxygenase (5-LOX) inhibition. This herbal composition with strong anti-5-LOX activity exhibited significant pain relief as indicated through improvements in weight-bearing capacity in a monosodium iodoacetate-induced osteoarthritis (OA) model of Sprague-Dawley rats. A 90-day randomized, placebo-controlled double-blind study evaluates the clinical efficacy and tolerability of LI73014F2 in the management of symptoms of OA of the knee (Clinical Trial Registration No. CTRI/2014/01/004338). Subjects, (n = 105), were randomized into three groups: placebo (n = 35), 200 mg/day of LI73014F2 (n = 35), and 400 mg/day of LI73014F2 (n = 35). All study participants were evaluated for pain and physical function by using standard tools, that is, Visual Analog Scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at the baseline (day 0) and on day 14 ± 3, 30 ± 3, 60 ± 3, and at the end of the study (day 90 ± 3). In addition, routine examinations on biochemical parameters in serum, urine, and hematological parameters were conducted on each visit to assess the safety of the study material. At the end of the trial period, LI73014F2 conferred significant pain relief, improved physical function, and quality of life in OA patients. In conclusion, preclinical and clinical data together strongly suggest that the herbal formulation LI73014F2 is a safe and effective intervention for management of joint discomfort, demonstrating efficacy as early as 14 days.

Topics: Aged; Animals; Body Mass Index; Body Weight; Boswellia; Curcuma; Cytokines; Disease Models, Animal; Double-Blind Method; Drug Synergism; Female; Follow-Up Studies; Humans; Hyperalgesia; Iodoacetic Acid; Lipoxygenase Inhibitors; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Plant Extracts; Quality of Life; Rats; Rats, Sprague-Dawley; Surveys and Questionnaires; Terminalia; Treatment Outcome; Visual Analog Scale

Curcumin is one of the most investigated phytochemical products because of its low toxicity and its broad spectrum of bioactivity, including anti-inflammatory and analgesic properties. A new delivery form of curcumin, resorting to phosphatidylcholine (Meriva®, formulated as the finished product Algocur®) has been developed to increase its bioavailability. In this study, we tested the efficacy and safety of a Meriva®-based product in rugby players suffering by different osteo-muscular pain conditions PATIENTS AND METHODS: In this pilot study, 50 male rugby players with osteo-muscular pain due to traumatic injuries, physical overload or acute episode of chronic pain were recruited and treated with conventional analgesic drugs (n = 25) or Meriva®-based product (n = 25) for a maximum of 10 days. The pain perception and the functio laesa were evaluated at baseline and after 1, 3, 6, 10 and 20 days from the initiation of the treatment protocol. Treatment tolerability, compliance, and adverse events were also reported.. During the study, the analgesic effect decreased in both treated group compared to baseline, starting from the third day of treatment. Similarly, the impaired physical function evaluated after 3, 6, 10 and 20 days improved in Meriva®-based product treated group and in subjects treated with conventional analgesic drugs, compared to the baseline condition. The percentage of excellent adherence to treatment or tolerability was higher in the Meriva®-based product treated group. Only 1 (4%) subject treated with Meriva®-based product experienced adverse events whereas 4 (16%) subjects treated with conventional analgesic drugs reported gastric pain as an adverse event.. Despite the small sample size and the group heterogeneity, this study suggests that the naturally-derived, curcumin-based delivery form, Meriva® (formulated as the finished product Algocur®), could represent a promising safe, analgesic remedy in painful osteo-muscular conditions associated with intense, high impact, physical activities.

Topics: Adult; Analgesics; Athletes; Curcumin; Drug Compounding; Humans; Lecithins; Male; Medication Adherence; Muscular Diseases; Pain; Pilot Projects; Young Adult

Oral curcumin decreases inflammatory cytokines and increases muscle regeneration in mice.. To determine effects of curcumin on muscle damage, inflammation and delayed onset muscle soreness (DOMS) in humans.. Seventeen men completed a double-blind randomized-controlled crossover trial to estimate the effects of oral curcumin supplementation (2.5 g twice daily) versus placebo on single-leg jump performance and DOMS following unaccustomed heavy eccentric exercise. Curcumin or placebo was taken 2 d before to 3 d after eccentric single-leg press exercise, separated by 14-d washout. Measurements were made at baseline, and 0, 24 and 48-h post-exercise comprising: (a) limb pain (1-10 cm visual analogue scale; VAS), (b) muscle swelling, (c) single-leg jump height, and (d) serum markers of muscle damage and inflammation. Standardized magnitude-based inference was used to define outcomes.. At 24 and 48-h post-exercise, curcumin caused moderate-large reductions in pain during single-leg squat (VAS scale -1.4 to -1.7; 90 %CL: ±1.0), gluteal stretch (-1.0 to -1.9; ±0.9), squat jump (-1.5 to -1.1; ± 1.2) and small reductions in creatine kinase activity (-22-29 %; ±21-22 %). Associated with the pain reduction was a small increase in single-leg jump performance (15 %; 90 %CL ± 12 %). Curcumin increased interleukin-6 concentrations at 0-h (31 %; ±29 %) and 48-h (32 %; ±29 %) relative to baseline, but decreased IL-6 at 24-h relative to post-exercise (-20 %; ±18 %).. Oral curcumin likely reduces pain associated with DOMS with some evidence for enhanced recovery of muscle performance. Further study is required on mechanisms and translational effects on sport or vocational performance.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Exercise; Humans; Inflammation; Interleukin-6; Male; Myalgia; Pain; Pain Measurement; Physical Education and Training; Psychomotor Performance; Treatment Outcome; Weight Lifting; Young Adult

Treatment of osteoarthritis (OA) is challenging owing to the inefficacy and long-term adverse events of currently available medications including non-steroidal anti-inflammatory drugs. Curcuminoids are polyphenolic phytochemicals with established anti-inflammatory properties and protective effects on chondrocytes. The aim of this study is to investigate the clinical efficacy of curcuminoids in patients suffering from knee OA. A pilot randomized double-blind placebo-control parallel-group clinical trial was conducted among patients with mild-to-moderate knee OA. Patients were assigned to curcuminoids (1500 mg/day in 3 divided doses; n = 19) or matched placebo (n = 21) for 6 weeks. Efficacy measures were changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analogue scale (VAS) and Lequesne's pain functional index (LPFI) scores during the study. There was no significant difference in age, gender, body mass index, and VAS, WOMAC and LPFI scores between the study groups at baseline (p > 0.05). Treatment with curcuminoids was associated with significantly greater reductions in WOMAC (p = 0.001), VAS (p < 0.001) and LPFI (p = 0.013) scores compared with placebo. With respect to WOMAC subscales, there were significant improvements in the pain and physical function scores (p < 0.001) but not stiffness score (p > 0.05). There was no considerable adverse effect in both groups. To conclude, curcuminoids represent an effective and safe alternative treatment for OA.

Topics: Aged; Anti-Inflammatory Agents; Curcumin; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Phytotherapy; Pilot Projects

Osteoarthritis (OA) is a major cause of physical disability and impaired quality of life. Non-steroidal anti-inflammatory drugs are the most used treatment for OA, but they are frequently associated to adverse events. Alternative therapies are under investigation for the treatment of OA. Meriva® is a lecithin delivery form of curcumin, a powerful promoter of anti-oxidant response studied in a number of conditions related to chronic inflammation and pain.. This 4-month observational study, conducted in a 'real-life' scenario, compares the association of Meriva and glucosamine (n=63) with chondroitin sulphate+glucosamine (n=61) in 124 patients with grade 1-2 OA of the knee.. Patients treated with Meriva+glucosamine had significantly higher Karnofsky Index and WOMAC score (both in the physical and emotional domains), compared to those in the chondroitin+glucosamine group. Noteworthy, the walking distance at the treadmill test after 1 month was also significantly higher in the meriva+glucosamine group; this advantage was sustained until the end of the study. Although the need for concomitant drugs and medical attention decreased in both groups, this reduction was more evident for patients treated with Meriva+glucosamine.. Taken together, the results of this study shows that the 4-month administration of the association of Meriva and glucosamine can result in a faster onset of action and improved outcomes than the administration of an association of chondroitin sulphate and glucosamine in patients with OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chondroitin Sulfates; Curcumin; Female; Glucosamine; Humans; Male; Middle Aged; Osteoarthritis, Knee; Pain; Quality of Life; Treatment Outcome

Curcuma longa Linn. is widely used for the treatment of disorders associated with inflammation and was evaluated for its safety and efficacy in the treatment of painful knee osteoarthritis (OA). This was a randomized, single blind, placebo-controlled trial. Total of 120 patients (37 males and 83 females) with primary knee OA received either placebo (400 mg twice daily) or NR-INF-02 (500 mg twice daily) or glucosamine sulphate (GS) (750 mg twice daily) alone or combination of NR-INF-02 and GS for 42 days. The efficacy was assessed during treatment period, on day 21 and day 42. The decrease in severity of pain symptom and function of affected knee as primary efficacy outcome measure was assessed by Visual Analog Scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale, respectively. The clinical examination of affected joint was measured by an orthopaedic specialist and using a Clinician Global Impression Change (CGIC) scale. The analysis of post-treatment scores following administration of NR-INF-02 using VAS, WOMAC, and CGIC at each clinical visit showed significant decrease (p < 0.05) compared to placebo. NR-INF-02 treated group showed a significant (p < 0.01) decrease in use of rescue medication, along with clinical and subjective improvement compared to placebo. The tolerability and acceptability profile of NR-INF-02 was better during the trial period. The study demonstrates safety and efficacy of NR-INF-02 as a useful treatment option for patients with primary painful knee OA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Curcuma; Female; Glucosamine; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Plant Extracts; Severity of Illness Index; Single-Blind Method; Treatment Outcome

The objective of this study was to determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement in patients with knee osteoarthritis.. The design and setting were a randomized controlled study at a university hospital in Bangkok, Thailand.. One-hundred and seven (107) patients with primary knee osteoarthritis (OA) with pain score of > or =5 were randomized to receive ibuprofen 800 mg per day or C. domestica extracts 2 g per day for 6 weeks. The main outcomes were improvement in pain on level walking, pain on stairs, and functions of knee assessed by time spent during 100-m walk and going up and down a flight of stairs. The adverse events were also recorded.. Fifty-two (52) and 55 patients were randomized to C. domestica extracts and ibuprofen groups, respectively. Baseline characteristics of the patients in both groups were not different. The mean scores of the aforementioned outcomes at weeks 0, 2, 4, and 6 were significantly improved when compared with the baseline values in both groups. There was no difference in those parameters between the patients receiving ibuprofen and C. domestica extracts, except pain on stairs (p = 0.016). No significant difference of adverse events between both groups was found (33.3% versus 44.2%, p = 0.36 in C. domestica extracts and ibuprofen groups, respectively).. C. domestica extracts seem to be similarly efficacious and safe as ibuprofen for the treatment of knee OA.

Topics: Aged; Curcuma; Female; Humans; Ibuprofen; Knee Joint; Male; Middle Aged; Osteoarthritis, Knee; Pain; Phytotherapy; Plant Extracts; Walking

Topics: Adult; Anti-Inflammatory Agents; Curcuma; Dietary Supplements; Humans; Pain; Pain Measurement; Plant Extracts

Curcuma latifolia Roscoe, a plant in the Curcuma genus, has been used as a food additive and folk medicine in Thailand to treat pelvic pain and improve premenstrual syndrome. Although it has been used for centuries, no scientific studies have proved its potential effects on inflammatory pain and central nervous system (CNS) safety profiles.. This study aimed to evaluate the potential effects of the ethanolic extract of C. latifolia rhizome on inflammatory pain in mice, together with its CNS safety profiles.. First, network pharmacology was employed to identify the role of bioactive constituents in C. latifolia on inflammatory pain. In addition, in vitro pharmacology was also evaluated to confirm the anti-inflammatory activity of C. latifolia extract at cellular levels in activated macrophages and microglia. Furthermore, the efficacy of the plant extract in attenuating formalin-induced pain-like behaviors in mice was evaluated. Mice were orally administered the extract (125, 250, 500 mg/kg) followed by the measurement of formalin-induced pain-like behaviors. The LABORAS automated behavioral analysis and rotarod test were used to assess potential CNS side effects of C. latifolia extract (500 mg/kg) in mice.. The results demonstrated that major bioactive constituents present in C. latifolia have the ability to regulate multiple targets, biological processes and pathways associated with inflammatory pain as assessed by network pharmacology. C. latifolia modulated peripheral and central immune cells via reducing proinflammatory mediators (NO, TNF-α, and IL-6). C. latifolia extract improved formalin-induced pain-like behaviors in a dose-dependent manner during phase II of the formalin test. The efficacy of the plant extract at doses of 250 and 500 mg/kg was comparable to that of the positive control (indomethacin 10 mg/kg). Furthermore, the highest therapeutic dose of the extract did not affect motor coordination, exploratory behaviors, general behaviors, and overall well-being of mice, indicating no development of potential CNS adverse effects after administration of the extract.. These findings provide novel perspectives on using C. latifolia extract for pain management, considering its therapeutic efficacy and CNS safety.

Topics: Analgesics; Animals; Central Nervous System; Curcuma; Female; Formaldehyde; Mice; Pain; Plant Extracts

Several clinical studies have reported the analgesic effect of curcumin (Curc) in various situations such as rheumatoid arthritis, osteoarthritis, and postsurgical pain. Therefore, in this work, Curc-loaded electrospun nanofibers (NFs) are designed to evaluate their sustained release on analgesic effect duration in rats after epidural placement via repeated formalin and tail-flick tests. The Curc-loaded polycaprolactone/gelatin NFs (Curc-PCL/GEL NFs) are prepared through an electrospinning technique and introduced to the rat's epidural space after laminectomy. The physicochemical and morphology features of the prepared Curc-PCL/GEL NFs were characterized via FE-SEM, FTIR, and degradation assay. The in vitro and in vivo concentrations of Curc were measured to evaluate the analgesic efficacy of the drug-loaded NFs. Rat nociceptive responses are investigated through repeated formalin and tail-flick tests for 5 weeks after the placement of NFs. Curc had a sustained release from the NFs for 5 weeks, and its local pharmaceutical concentrations were much greater than plasma concentrations. Rat's pain scores in both early and late phases of the formalin test were remarkably decreased in the experimental period. Rat's tail-flick latency was remarkably enhanced and remained constant for up to 4 weeks. Our findings show that the Curc-PCL/GEL NFs can supply controlled release of Curc to induce extended analgesia after laminectomy.

Topics: Analgesia; Analgesics; Animals; Curcumin; Delayed-Action Preparations; Formaldehyde; Gelatin; Laminectomy; Nanofibers; Pain; Polyesters; Rats

A library of

Topics: Acetylcholinesterase; Alzheimer Disease; Antioxidants; Cholinesterase Inhibitors; Curcumin; Donepezil; Humans; Molecular Docking Simulation; Pain; Structure-Activity Relationship

Curcumin is one of the compounds present in plants of the genus Curcuma sp., being very used not only as condiment but also with medicinal purposes. As an analgesic, papers highlight the efficacy of curcumin in the treatment of various types of pain.. In this study we evaluated the peripheral antinociceptive effect of curcumin and by which mechanisms this effect is induced.. The mice paw pressure test was used on animals which had increased pain sensitivity by intraplantar injection of carrageenan. All the drugs were administered in the right hind paw.. Curcumin was administered to the right hind paw animals induced antinociceptive effect. Non -selective antagonist of opioid receptors naloxone reverted the antinociceptive effect induced by curcumin. Selective antagonists for μ, δ and κ opioid receptors clocinnamox, naltrindole and nor- binaltorphimine, respectively, reverted the antinociceptive effect induced by curcumin. Bestatin, enkephalinases inhibitor that degrade peptides opioids, did not change the nociceptive response. Selective antagonists for CB. These results suggest that curcumin possibly peripheral antinociception induced by opioid and cannabinoid systems activation and possibly for endocannabinoids and opioids release.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Cannabinoid Receptor Agonists; Carrageenan; Cinnamates; Curcumin; Dose-Response Relationship, Drug; Endocannabinoids; Hyperalgesia; Male; Mice; Morphine Derivatives; Narcotic Antagonists; Pain; Polyunsaturated Alkamides; Receptors, Opioid

Stress is a condition affecting different body systems. Curcumin (CUR) is a natural compound that has various pharmacological benefits. However, its poor oral bioavailability limits its therapeutic value. This study aimed to formulating curcumin loaded chitosan nanoparticles (CS.CUR.NPs) and investigate its gastroprotective and neuroprotective effects in rats subjected to cold restraint stress (CRS), in reference to conventional oral CUR preparation, and explore its underlying mechanism. Treated groups received either CUR or CS.CUR.NPs (100 mg∕kg) orally for 14 days before exposure to CRS. CRS elicited marked behavioral changes and gastric ulcer accompanied by histopathological abnormalities of the brain and stomach along with elevation of pain score. CUR and CS.CUR.NPs improved stress-induced gastric ulcer, cognitive performance, and pain sensation. Mechanistically, CRS disrupts oxidative and inflammatory status of the brain as manifested by high malondialdehyde and IL-6 and low total antioxidant capacity and IL-10, along with high C-reactive protein level. CRS decreased nuclear factor erythroid 2-related factor2 (Nrf2) and increased nuclear factor-kappa B (NF-κB) expressions. Furthermore, brain levels of unphosphorylated signal transducer and activator of transcription3 (U-STAT3) and glial fibrillary acidic protein (GFAP) were upregulated with stress. CUR and CS.CUR.NPs provided beneficial effects against harmful consequences resulting from stress with superior beneficial effects reported with CS.CUR.NPs. In conclusion, these findings shed light on the neuroprotective effect of CUR and CS.CUR.NPs against stress-induced neurobehavioral and neurochemical deficits and protection against stress-associated gastric ulcer. Moreover, we explored a potential crosslink between neuroinflammation, U-STAT3, NF-κB, and GFAP in brain dysfunction resulted from CRS.

Topics: Animals; Behavior, Animal; Chitosan; Cognitive Dysfunction; Cold Temperature; Curcumin; Glial Fibrillary Acidic Protein; Inflammation; Nanoparticle Drug Delivery System; Neuroprotective Agents; Oxidation-Reduction; Pain; Rats; STAT3 Transcription Factor; Stomach; Stomach Ulcer; Stress, Physiological

Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED

Topics: Analgesics; Anti-Inflammatory Agents; Curcumin; Humans; Metformin; Pain

Osteoarthritis (OA) of the hand is a common painful musculoskeletal disorder with no cure. There is a need for an efficient and safe treatment to relieve OA pain.. To investigate the effects of a. This open-label, non-controlled, post-observational study was based on 232 patients suffering from hand pain with or without joint deformity. Patients received a medical prescription for a three-month treatment with a food supplement containing 89 mg of. This is the first clinical trial showing that

Topics: Anti-Inflammatory Agents, Non-Steroidal; Boswellia; Curcuma; Humans; Osteoarthritis; Pain; Plant Extracts; Resins, Plant

A series of curcumin bis-conjugates 3a-q, 5a-k and 6a-k were synthesized in good yields utilizing an optimized reaction condition. We explored the effect of different amino acids and protecting groups on biological activities of curcumin. The conjugates were screened for anti-inflammatory, analgesic and antimicrobial properties. Some of the conjugates showed promising biological observations with a potency comparable with the standard references. The variations in biological properties concerning different amino acids and protecting groups are interesting observations. Effects of the synthesized conjugates on splenocytes and the production of nitric oxide by lipopolysaccharide-stimulated peritoneal macrophages are correlated with the observed anti-inflammatory properties. We have also established the safety profile of the most active conjugates. Robust 2D-QSAR studies supported and validated biological data.

Topics: Amino Acids; Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Candida albicans; Carrageenan; Cell Proliferation; Curcumin; Dose-Response Relationship, Drug; Edema; Mice; Microbial Sensitivity Tests; Molecular Structure; Pain; Pseudomonas aeruginosa; Quantitative Structure-Activity Relationship; Rats; Salmonella typhi; Spleen; Staphylococcus aureus; Streptococcus pyogenes; Ulcer

Topics: Curcuma; Double-Blind Method; Humans; Osteoarthritis, Knee; Pain; Plant Extracts

Topics: Curcuma; Double-Blind Method; Humans; Osteoarthritis, Knee; Pain; Plant Extracts

Topics: Curcuma; Double-Blind Method; Humans; Osteoarthritis, Knee; Pain; Plant Extracts

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 μL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Topics: Animals; Anti-Inflammatory Agents; Arthralgia; Arthritis, Experimental; Cartilage, Articular; Collagen Type II; Curcuma; Cytokines; Disease Models, Animal; Edema; Female; Indomethacin; Inflammation; Iodoacetates; Joint Diseases; Knee Joint; Osteoarthritis; Pain; Plant Extracts; Rats; Rats, Wistar; Zingiber officinale

Topics: Curcumin; Humans; Inflammation; Mefenamic Acid; Molar; Molar, Third; Pain; Tooth Extraction; Tooth, Impacted

Tagetes lucida Cav. is an ancient medicinal plant used to treat different ailments involving neurological diseases and pain. However, scientific studies to validate their medicinal properties as analgesic have not been described. The aim of this study was to evaluate the T. lucida antinociceptive response using pain models. Bioactive compounds and a possible mechanism of action were also explored. Dose-response effects of an ethanol crude extract were investigated in the writhing and formalin tests in mice and rats, respectively. The extract was fractionated to isolate active fractions and bioactive compounds (quercetagetin 7‑O‑β‑d‑glucoside and 6,7‑dimethoxycoumarin) using the formalin test. The antinociceptive effects were compared to the reference drugs (tramadol 10 mg/kg, diclofenac 50 mg/kg, and/or ketorolac 1 mg/kg, i.p.). The ethanol extract was explored in the presence of naloxone (3 mg/kg, i.p. a non-selective opioid receptor antagonist) and WAY100635 (0.5 mg/kg, s.c., a selective 5-HT

Topics: Analgesics; Animals; Curcumin; Female; Flavones; Male; Medicine, Chinese Traditional; Mice; Models, Animal; Naloxone; Narcotic Antagonists; Pain; Plant Extracts; Plant Leaves; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A; Tagetes

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Topics: Animals; Antioxidants; Curcumin; Disease Models, Animal; Drug Therapy, Combination; Inflammation; Male; Migraine Disorders; Naproxen; Oxidative Stress; Pain; Pain Measurement; Rats; Rats, Wistar

Curcuma Longa Radix (Huangsiyujin in Chinese, HSYJ) has been used in clinical for thousands of years as a traditional Chinese medicine (TCM) and has the effects of invigorating the blood circulation, relieving pain, promoting qi circulation and relieving depression, besides, it is able to clear heart heat and cool blood and cure jaundice. The study aims to determine the active fractions of HSYJ for promotion of blood circulation and relief of pain, and to identify their chemical constituents.. HSYJ was extracted by the systematic solvent method. The effects of promoting blood circulation and relieving pain were determined by measuring pain threshold (hot-plate test), latency of twisting and writhing times (acetic acid induced writhing test), and hemorheology of mice. Chemical constituents of the extractive fractions were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS) or High Performance Liquid Chromatography (HPLC).. The results showed that five fractions (volatile oil fraction, petroleum ether fraction, ethyl acetate fraction, 1-butanol fraction and water fraction) all could increase pain threshold, prolong latency of twisting, decrease the writhing times and influence hemorheology. However, the effects of the volatile oil fraction and ethyl acetate fraction were better than other fractions. Three constituents, namely bisdesmethoxycurum, desmethoxycurumin and curcumin were identified from the active fractions by comparing with standard preparation through HPLC analysis. Forty-five compounds including aR-Turmerone, Curlone, Tumerone, Cyclohexene,1-methyl-4-(1-methylethylidene)-, trans-Sesquisabinene hydrate, (E)-Atlantone, α-curcumene and Zingiberene were identified from the volatile oil fraction by GC-MS.. HSYJ possessed the effect of promoting blood circulation and relieving pain. Curcumins and their derivatives were the major constituents and might be the main bioactive ingredients for the promotion of blood circulation and relief of pain. The study provided evidence and formed a basis for the establishment of HSYJ comprehensive quality evaluation system related to traditional efficacy. It is beneficial to the quality control of HSYJ and its proprietary Chinese medicine.

Topics: Animals; Blood Circulation; Chromatography, High Pressure Liquid; Curcuma; Disease Models, Animal; Drugs, Chinese Herbal; Female; Gas Chromatography-Mass Spectrometry; Male; Mice; Pain; Pain Threshold; Plant Extracts

Endometriosis is characterized by disabling symptoms that afflict young women with severe physical discomfort, difficulty in relationship life, and infertility; however, the currently available therapeutic strategies are unsatisfactory. Goal of this research was to identify a new combination of natural active ingredients that, administered as dietary supplements, could have the effect of reducing inflammatory response in endometriosis patients, decreasing the symptoms the disease produces and its harmful effects on affected organs. A cohort of endometriosis patient was treated for 3 months with a composition including quercitin, curcumin, parthenium, nicotinamide, 5-methyltetrahydrofolate, and omega 3/6. Using a VAS scale, we demonstrated a significant reduction of the symptoms in endometriosis patients treated with the dietary composition respect to the controls. Moreover, we demonstrated also a significant reduction in the serum levels of PGE2 and CA-125. Further study are required to compare the effect of this combination of molecules with standard therapies and to evaluate if the use of these dietary supplements in combination with standard therapies may lead to the improvement of the regular medical treatment for endometriosis.

Topics: Adult; Curcumin; Dietary Supplements; Endometriosis; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Niacinamide; Pain; Parthenogenesis; Plant Extracts; Quercetin; Tetrahydrofolates

Effects of curcumin, a major ingredient of turmeric, were tested on the function of the

Topics: Allosteric Regulation; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzamides; Bridged Bicyclo Compounds; Curcumin; Disease Models, Animal; Female; Inflammation; Male; Mice; Motor Activity; Nociception; Pain

Topics: Administration, Oral; Anemia, Sickle Cell; Animals; Antioxidants; Astrocytes; Curcumin; Disease Models, Animal; Female; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Humans; Hyperalgesia; Mice; Mice, Transgenic; Microglia; Neurons; Neuropeptides; Nociception; Oxidative Stress; Pain; Reactive Oxygen Species; Spinal Cord Dorsal Horn; Ubiquinone

Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM).. Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing.. Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1β and TNF-α, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1β. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle-treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior.. This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model.

Topics: Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Cartilage, Articular; Chondrocytes; Curcumin; Disease Progression; Female; Gene Expression Profiling; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Middle Aged; Nanoparticles; Osteoarthritis; Pain; Real-Time Polymerase Chain Reaction; Transcriptome

Topics: Curcumin; Humans; Muscle, Skeletal; Myalgia; Pain

Curcumin is a major component of turmeric and reportedly has anti-inflammatory and anti-oxidant effects. Neuroinflammation has been recognized to play an important role in the pathogenesis of various diseases in the central nervous system. Here we investigated the anti-nociceptive and anti-neuroinflammatory effect of curcumin on arthritic pain in rats. We found that repeated oral treatment with curcumin, either before or after complete Freund's adjuvant (CFA) injection, dose-dependently attenuated CFA-induced mechanical allodynia and thermal hyperalgesia, but had no effect on joint edema. Repeated intrathecal injection of curcumin reversed CFA-induced pain hypersensitivity. Furthermore, such a curcumin treatment reduced CFA-induced activation of glial cells and production of inflammatory mediators [interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and monocyte inflammatory protein-1 (MIP-1α)] in the spinal cord. Curcumin also decreased lipopolysaccharide-induced production of IL-1β, tumor necrosis factor-α, MCP-1, and MIP-1α in cultured astrocytes and microglia. Our results suggest that intrathecal curcumin attenuates arthritic pain by inhibiting glial activation and the production of inflammatory mediators in the spinal cord, suggesting a new application of curcumin for the treatment of arthritic pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Astrocytes; Cells, Cultured; Chemokine CCL2; Chemokine CCL3; Curcumin; Hyperalgesia; Inflammation; Injections, Spinal; Interleukin-1beta; Lipopolysaccharides; Male; Microglia; Pain; Rats; Rats, Sprague-Dawley; Spinal Cord; Spine

This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice.. Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus.. KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05.. Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression.. Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.

Topics: Animals; Antioxidants; Curcumin; Cytokines; Heme Oxygenase-1; Hyperalgesia; Injections, Subcutaneous; Leukocytes; Male; Membrane Glycoproteins; Mice; NADPH Oxidase 2; NADPH Oxidases; NF-E2-Related Factor 2; NF-kappa B; Oxidants; Oxidative Stress; Oxides; Pain; Potassium Compounds; RNA, Messenger; Superoxides

The rhizome of Curcuma amada has been used as a folk medicine for the treatment of rheumatic disorders in the northern part of Bangladesh and has also used for the treatment of inflammation and fever in the Ayurvedic and Unani systems of medicine. Aim of the study was to investigate the analgesic principle of the MeOH extract of the rhizome of Curcuma amada by an in vivo bioassay guided chromatographic separation and purification, and the structure elucidation of the purified compound by spectroscopic methods.. Dried powder of Curcuma amada rhizomes was extracted with MeOH. The analgesic activity of the crude extract and its chromatographic fractions as well as the purified compound itself was evaluated by the acetic acid induced writhing method and the formalin induced licking test in Swiss albino mice. The MeOH extract was separated by chromatographic methods and the pure active compound was purified by crystallization in hexanes. The structure of the pure compound was then elucidated by spectroscopic methods.. The MeOH extract of Curcuma amada exhibited 41.63% and 45.53% inhibitions in the acetic acid induced writhing method at doses of 200mg/kg and 400mg/kg, respectively. It also exerted 20.43% and 28.50% inhibitions in early phase at doses of 200mg/kg and 400mg/kg, respectively, and 30.41% and 42.95% inhibitions in late phase at doses of 200mg/kg and 400mg/kg, respectively in the formalin induced licking test. Vacuum Liquid Chromatography (VLC) of crude extract yielded five fractions and Fr. 1 was found to have the most potent analgesic activity with inhibitions of 36.96% in the acetic acid induced writhing method and 47.51% (early phase), 39.50% (late phase) in the formalin induced licking test at a dose of 200mg/kg. Column chromatography of Fr. 1 on silica gel generated seven fractions (SF. 1-SF. 7). SF. 2 showed the most potent activity with inhibition of 49.81% in the acetic acid induced writhing method at a dose of 100mg/kg. Crystallization of SF. 2 yielded (1) (zederone, 520mg). It showed statistically significant inhibitions of 38.91% and 52.14% in the acetic acid induced writhing method at doses of 20mg/kg and 40mg/kg, respectively. Moreover, it also showed statistically significant inhibitions of 27.79% and 29.93% (early phase) and of 38.24% and 46.08% (late phase) in the formalin induced licking test at doses of 20mg/kg and 40mg/kg, respectively.. Isolation and characterization of zederone (1) as analgesic principle of Curcuma amada corroborate its use in Ayurvedic, Unani and folk medicines for the treatment of rheumatic disorders and also contributing to its pharmacological validation.

Topics: Acetic Acid; Analgesics; Animals; Curcuma; Female; Formaldehyde; Male; Mice; Pain; Plant Extracts; Rhizome; Sesquiterpenes

The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain.

Topics: Analgesics; Animals; Curcumin; Diclofenac; Drug Synergism; Female; Formaldehyde; Pain; Pain Measurement; Rats, Wistar

The present study was aimed to investigate the antinociceptive and anti-inflammatory activity of the Curcuma zedoaria (family Zingiberaceae) ethanolic rhizome extract in laboratory using both in vitro and in vivo methods so as to justify its traditional use in the above mentioned pathological conditions.. Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo antinociceptive activity was performed employing the hot plate method, acidic acid induced writhing test and formalin induced writhing test on Swiss albino mice at doses of 250 and 500 mg/kg body weight. Anti-inflammatory activity test was done on Long Evans rats at two different doses (250 and 500 mg/kg body weight) by using carrageenan induced paw edema test. Finally in vitro anti-inflammatory test by protein-denaturation method was followed. Data were analyzed by one-way analysis of variance (ANOVA) and Dunnett's t-test was used as the test of significance. P value <0.05 was considered as the minimum level of significance.. Phytochemical screening revealed presence of tannins, saponins, flavonoids, gums & carbohydrates, steroids, alkaloids, reducing sugars and terpenoids in the extract. In the hot plate method, the extract increased the reaction time of heat sensation significantly to 61.99% and 78.22% at the doses of 250 and 500 mg/kg BW respectively. In acetic acid induced writhing test, the percent inhibition of writhing response by the extract was 48.28% and 54.02% at 250 and 500 mg/kg doses respectively (p < 0.001). The extract also significantly inhibited the licking response in both the early phase (64.49%, p < 0.01) and the late phase (62.37%, p < 0.01) in formalin induced writhing test. The extract significantly (p < 0.05, p < 0.01 and p < 0.001) inhibited carrageenan induced inflammatory response in rats in a dose related manner. In in-vitro anti-inflammatory test, the extract significantly inhibited protein denaturation of 77.15, 64.43, 53.04, 36.78 and 23.70% for doses of 500, 400, 300, 200 and 100 μg/mL respectively.. The results obtained from the tests indicate that the plant might have one or more secondary metabolite(s) having central and peripheral analgesic and anti-inflammatory activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Curcuma; Edema; Female; Humans; Male; Mice; Pain; Plant Extracts; Rats; Rats, Long-Evans; Rhizome

Curcumin has shown to be effective against various diabetes related complications. However major limitation with curcumin is its low bioavailability. In this study we formulated and characterized self nano emulsifying drug delivery system (SNEDDS) curcumin formulation to enhance its bioavailability and then evaluated its efficacy in experimental diabetic neuropathy. Bioavailability studies were performed in male Sprague Dawley rats. Further to evaluate the efficacy of formulation in diabetic neuropathy various parameters like nerve function and sensorimotor perception were assessed along with study of inflammatory proteins (NF-κB, IKK-β, COX-2, iNOS, TNF-α and IL-6). Nanotechnology based formulation resulted in prolonged plasma exposure and bioavailability. SNEDDS curcumin provided better results against functional, behavioural and biochemical deficits in experimental diabetic neuropathy, when compared with naive curcumin. Further western blot analysis confirmed the greater neuroprotective action of SNEDDS curcumin. SNEDDS curcumin formulation due to higher bioavailability was found to afford enhanced protection in diabetic neuropathy.. In this study the authors formulated and characterized a self-emulsifying drug delivery system for formulation to enhance curcumin bioavailability in experimental diabetic neuropathy. Enhanced efficacy was demonstrated in a rat model.

Topics: Animals; Biological Availability; Curcumin; Diabetic Neuropathies; Drug Delivery Systems; Emulsions; Humans; Male; Nanoparticles; Neuroprotective Agents; Pain; Rats

This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.

Topics: Analgesics; Animals; Curcumin; Cyclohexanones; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Inhibitory Concentration 50; Injections, Intraperitoneal; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pain; Toxicity Tests, Acute

An apparent clinical relationship between pain and depression has long been recognized. Depression and pain are often diagnosed in the same patients. The emerging concept for pain-depression pathogenesis is the dysfunction of biogenic amine-mediated pain-depression control and the possible involvement of nitrodative stress-induced neurogenic inflammation. The present study was designed to investigate the effect of curcumin on reserpine-induced pain-depression dyad in rats. Administration of reserpine (1mg/kg subcutaneous daily for three consecutive days) led to a significant decrease in nociceptive threshold as evident from reduced paw withdrawal threshold in Randall Sellitto and von-Frey hair test as well as significant increase in immobility time in forced swim test. This behavioural deficit was integrated with decrease in the biogenic amine (dopamine, norepinephrine and serotonin) levels along with increased substance P concentration, nitrodative stress, inflammatory cytokines, NF-κβ and caspase-3 levels in different brain regions (cortex and hippocampus) of the reserpinised rats. Curcumin (100, 200, 300mg/kg; ip) dose dependently ameliorated the behavioural deficits associated with pain and depression by restoring behavioural, biochemical, neurochemical and molecular alterations against reserpine-induced pain-depression dyad in rats.

Topics: Adrenergic Uptake Inhibitors; Animals; Antidepressive Agents; Behavior, Animal; Biomarkers; Curcumin; Depression; Male; Models, Biological; Molecular Diagnostic Techniques; Neurochemistry; Pain; Rats; Rats, Wistar; Reserpine

Mango ginger (Curcuma amada Roxb.) is a unique spice having morphological resemblance with ginger but imparts a raw mango flavour. The main use of mango ginger rhizome is in the manufacture of pickles and culinary preparations. Ayurveda and Unani medicinal systems have given much importance to mango ginger as an appetizer, alexteric, antipyretic, aphrodisiac, diuretic, emollient, expectorant and laxative and to cure biliousness, itching, skin diseases, bronchitis, asthma, hiccough and inflammation due to injuries. The biological activities of mango ginger include antioxidant activity, antibacterial activity, antifungal activity, anti-inflammatory activity, platelet aggregation inhibitory activity, cytotoxicity, antiallergic activity, hypotriglyceridemic activity, brine-shrimp lethal activity, enterokinase inhibitory activity, CNS depressant and analgesic activity. The major chemical components include starch, phenolic acids, volatile oils, curcuminoids and terpenoids like difurocumenonol, amadannulen and amadaldehyde. This article brings to light the major active components present in C. amada along with their biological activities that may be important from the pharmacological point of view.

Topics: Analgesics; Anti-Allergic Agents; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antiemetics; Antioxidants; Bacteria; Curcuma; Curcumin; Humans; Hydroxybenzoates; Hypersensitivity; Inflammation; Microbial Sensitivity Tests; Oils, Volatile; Pain; Plant Extracts; Rhizome; Skin Diseases; Terpenes

The effects of Curcuma mangga ethanolic extract (CME) and its fractions, e.g., aqueous, chloroform, ethyl acetate, and hexane fractions, from C. mangga rhizome were investigated on nociceptive responses using writhing, hot plate, and formalin tests in mice and inflammatory models using carrageenan-induced rat paw edema and croton oil-induced mouse ear edema. The results showed that CME and all fractions (200 mg/kg, p.o.) significantly reduced the number of writhings. Oral administration (p.o.) of CME, chloroform, and hexane fractions (200 mg/kg) significantly prolonged the latency time, whereas aqueous and ethyl acetate fractions were inactive. The activities of CME, chloroform, and hexane fractions were abolished by naloxone (2 mg/kg, intraperitoneal (i.p.)). CME and all fractions at the dose of 200 mg/kg significantly produced antinociception in both early and late phases of the formalin test. CME, chloroform, and hexane fractions were more prominent in licking inhibition than those of the aqueous and ethyl acetate fractions. CME and all fractions (150 mg/kg, p.o.) showed significant reduction of rat paw edema. The order of activity on inhibition of paw edema at 4 h was chloroform fraction > hexane fraction > ethyl acetate fraction > CME > aqueous fraction. When topically applied at 0.5 mg/ear, CME and all fractions suppressed ear edema induced by croton oil. CME and chloroform fraction showed a greater inhibition by 53.97 and 50.29%, respectively. These results suggested that CME and its fractions, especially chloroform and hexane fractions from C. mangga rhizome, possessed centrally acting analgesic as well as anti-inflammatory activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Curcuma; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Inflammation; Male; Mice; Pain; Plant Extracts; Rats; Rhizome; Solvents

Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol. The analgesic activity was studied in rats using three different models, namely the hot plate test, tail flick test and formalin-induced pain test. The acute oral toxicity was examined by the oral administration of standardized Curcuma xanthorrhiza ethanolic extract in mice at doses ranging from 300-5,000 mg/kg and observation for 14 days. Standardized Curcuma xanthorrhiza ethanolic extract did not show significant analgesic effect in the hot plate and tail flick tests. However, in the formalin-induced pain test, Curcuma xanthorrhiza ethanolic extract significantly (P < 0.05) suppressed the paw licking time of rats in both early and late phases at doses 200 and 400 mg/kg of the extract, respectively. In the acute oral toxicity study, Curcuma xanthorrhiza ethanolic extract did not show any toxic effects in mice at 5 g/kg. These experimental results suggest that the standardized Curcuma xanthorrhiza ethanolic extract showed peripheral and central antinociceptive activity associated with neurogenic pain as well as a relative absence of toxic effects which could compromise the medicinal use of this plant in folk medicine.

Topics: Administration, Oral; Analgesics; Animals; Curcuma; Ethanol; Female; Male; Mice; Mice, Inbred ICR; Pain; Plant Extracts; Rats; Rats, Sprague-Dawley; Rhizome

In the present study, the effect of chronic oral administration of curcumin in the presence or absence of morphine and noloxone was investigated on the visceral nociception induced by acetic acid in rats. Intraperitoneal injection of acetic acid (1 mL, 2%) produced contractions in the abdominal musculature (writhes). The latency time to the beginning of the first writhe was measured and the total number of writhes in the 1 h after acetic acid injection was counted. The latency time to the beginning of the first writhe was significantly (p < 0.05) increased and the number of writhes was significantly (p < 0.05) decreased by curcumin (20 and 40 mg kg(-1) body weight). The same results were obtained after subcutaneous injection of morphine (1 mg kg(-1) b.wt.). Naloxone at the dose of 1 mg kg(-1) body weight had no effect on pain intensity. Curcumin significantly (p < 0.05) enhanced the effect of morphine on the visceral pain responses, however did not reverse the effect of naloxone. Present data suggest that in the acetic acid-induced visceral nociception of rats, curcumin may produce an antinociceptive effect and the endogenous analgesic opioid system is involved in the curcumin-induced antinociception.

Topics: Acetic Acid; Animals; Curcumin; Male; Pain; Pain Measurement; Rats; Rats, Wistar

In this study, the effect of curcumin on the formalin-induced pain was investigated in rats. Interaction between curcumin and opioid system using morphine and naloxone was also examined. A biphasic pain response was induced after intraplantar injection of formalin (50 microL, 1%). Curcumin, morphin and naloxone had no effect on the early phase of pain. Late phase of pain was suppressed by curcumin at the doses of 100 and 200 mg kg(-1) body weigh. Morphine (1 mg kg(-1) BW) reduced, whereas naloxone (1 mg kg(-1) BW) did not affect the late phase of pain. Currcumin did not influence the morphine-induced antinociception, but reversed the effect of naloxone on pain. Present findings indicate that curcumin may produce antinociception by activation of both opioid and non opioid mechanisms of pain.

Topics: Analgesics, Opioid; Animals; Antineoplastic Agents; Curcumin; Male; Morphine; Naloxone; Pain; Pain Measurement; Rats; Rats, Wistar; Receptors, Opioid

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Drug Therapy, Combination; Hot Temperature; Insulin; Male; Mice; Nitric Oxide; Pain; Pain Measurement; Phytotherapy; Plant Extracts; Plants, Medicinal; Resveratrol; Stilbenes; Streptozocin; Tumor Necrosis Factor-alpha

To clarify the properties of BL-2401 ((+/-)-3-[2-benzyl-3-(propionylthio) propionyl]amino-5-methylbenzoic acid), a novel enkephalinase inhibitor, we examined its antinociceptive and antidepressant-like activities after oral administration, along with their association with endogenous opioid systems. BL-2401 produced an antinociceptive effect after oral administration in the mouse phenylbenzoquinone writhing test (ED50: 12.4 mg/kg) and the rat acetic acid writhing test (ED50: 55.8 mg/kg), the antinociceptive effect being antagonized by naloxone hydrochloride. BL-2401 also relieved arthritis-induced hyperalgesia in rats. In the mouse hot-plate and tail pressure tests, BL-2401 showed significant but modest antinociception at higher doses (200 and 400 mg/kg). In addition, BL-2401 (100 mg/kg) produced a naloxone-reversible antidepressant-like effect in the mouse forced swimming test. As for the mechanism of the action, the active metabolite of BL-2401, BL-2240 ((+/-)-3-(2-benzyl-3-mercaptopropionyl) amino-5-methylbenzoic acid), selectively inhibited enkephalinase in vitro (IC50: 5.2 nM). Oral administration of BL-2401 to mice significantly inhibited the enkephalinase activity in the striatum and also potentiated the antinociceptive effect of (D-Ala2,Met5)-enkephalin given intracisternally. These findings indicate that BL-2401 is an orally active enkephalinase inhibitor and may produce antinociceptive and antidepressant-like effects in association with endogenous opioid systems.

Topics: Administration, Oral; Analgesics; Analgesics, Opioid; Animals; Antidepressive Agents; Benzoates; Benzoquinones; Corpus Striatum; Curcumin; Dose-Response Relationship, Drug; Drug Synergism; Enkephalin, Methionine; Female; Hyperalgesia; Male; Mice; Naloxone; Narcotic Antagonists; Narcotics; Neprilysin; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sulfhydryl Compounds; Swimming