Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Actinic Keratoses (AKs) are epidermal skin lesions that have the potential to develop into squamous cell carcinoma. Many of the treatment options available can cause discomfort, pain or skin irritation. Topical 3% diclofenac in 2.5% hyaluronan gel (Solaraze, Bioglan Pharma) is a relatively new treatment that has been shown to be effective and well tolerated for the treatment of AKs.
 ...
PMID:Topical 3% diclofenac in 2.5% hyaluronan gel for the treatment of actinic keratoses. 1471 39

The skin is the main target tissue for exogenous noxes, protecting us from harmful environmental hazards, UV-irradiation and endogenous water loss. It is composed of three layers, whereas the outermost epidermis is a squamous epithelium that mainly consists of keratinocytes. These cells execute a terminal differentiation, which finally results in the assembly of the stratum corneum. This layer, consisting of cornified keratinocytes, is an effective barrier against a vast number of substances. Apart of this, keratinocytes play crucial roles in the immune surveillance and the initiation, modulation and regulation of inflammation in the epidermis. Regarding cutaneous inflammatory reactions, skin irritation is one of the most common adverse effect in humans. For reasons of human safety assessment new chemicals are still evaluated for irritant potentials by application to animals followed by visible changes such as erythema and oedema. Testing for skin irritation in animals potentially cause them pain and discomfort. Furthermore, the results are not always predictive for those found in humans. In order to replace animal testing and to improve the prediction of irritants, the cosmetic and toiletry industry, in Europe represented by Colipa, develops and uses several alternative in vitro test systems. In this respect, the use of in vitro reconstructed organotypic skin equivalents are mostly favored, because of their increasingly close resemblance to human skin. Due to ethical and scientific questions and on account of the 7th amendment of the European Council Directive 76/768/EEC, the authors see the requirement to drive the development of alternative tests for irritants. Therefore, this article centres on cosmetic ingredients and provides the readership an overview of the state of art of cellular mechanisms of skin irritation and summarizes the results of the commonly used skin equivalents to evaluate irritation in vitro.
 ...
PMID:In vitro skin irritation: facts and future. State of the art review of mechanisms and models. 1504 69

This randomized, double-blind study was designed to evaluate the effectiveness of the topical cream Theraflex-TMJ (NaBob/Rx, San Mateo, CA) in patients with masseter muscle pain and temporomandibular joint (TMJ) pain. Fifty-two subjects (5 males and 47 females) were instructed to apply a cream over the afflicted masseter muscle(s) or over the jaw joint(s) twice daily for two weeks. Theraflex-TMJ cream was used by the experimental group, while a placebo cream was used by the control group. The means of pain ratings were calculated prior to the application of the cream (baseline), after ten days of tx (period 1), and 15 days of tx (period 2) days of treatment and five days after stopping the treatment (follow-up). There was a significant decrease in reported pain levels from baseline in the experimental group for period 1 (p < 0.01), period 2 (p < 0.001), and follow-up (p < 0.01). For the control group, no significant differences were found between the different time periods (p > 0.05). There was evidence of minor side effects such as skin irritation and/or burning on the site of the application in two subjects in the experimental as well as two subjects in the control groups. The data strongly suggest that Theraflex-TMJ topical cream is safe and effective for reducing pain in the masseter muscle and the temporomandibular joint.
 ...
PMID:Use of Theraflex-TMJ topical cream for the treatment of temporomandibular joint and muscle pain. 1513 14

Cold hyperalgesia is a major clinical phenomenon, but validated experimental models are still lacking for humans. Topical menthol application has recently been proposed as a possible model for the study of cold pain. We characterized the psychophysical effects of 30% l-menthol in ethanol on glabrous skin in 39 healthy subjects, using a double-blind, randomized, crossover design, with ethanol as a control. Psychophysical testing included an assessment of pain thresholds and detection of mechanical, cold, and heat stimuli, and of the sensations induced by suprathreshold stimuli. Most subjects (90%) perceived a cooling sensation with menthol. Menthol decreased cold pain thresholds and enhanced pain responses to suprathreshold noxious cold stimuli, without affecting responses to other stimuli. Menthol therefore has selective effects on noxious cold processing. No subject displayed signs of skin irritation or redness. These data suggest that 30% menthol application may be a useful experimental model for studies of cold hyperalgesia in humans. The absence of local skin reactions also makes this test potentially suitable for use in patients.
Pain 2006 May
PMID:Psychophysical study of the effects of topical application of menthol in healthy volunteers. 1652 5

In the field of consumer-used cosmetics for hair removal and hair growth reduction, there is a need for improved quantitative methods to enable the evaluation of efficacy and claim support. Optimized study designs and investigated endpoints are lacking to compare the efficacy of standard methods, like shaving or plucking, with new methods and products, such as depilating instruments or hair-growth-reducing cosmetics. Non-invasive image analysis, using a high-performance microscope combined with an optimized image analysis tool, was investigated to assess hair growth. In one step, high-resolution macrophotographs of the legs of female volunteers after shaving and plucking with cold wax were compared to observe short-term hair regrowth. In a second step, images obtained after plucking with cold wax were taken over a long-term period to assess the time, after which depilated hairs reappeared on the skin surface. Using image analysis, parameters like hair length, hair width, and hair projection area were investigated. The projection area was found to be the parameter most independent of possible image artifacts such as irregularities in skin or low contrast due to hair color. Therefore, the hair projection area was the most appropriate parameter to determine the time of hair regrowth. This point of time is suitable to assess the efficacy of different hair removal methods or hair growth reduction treatments by comparing the endpoint after use of the hair removal method to be investigated to the endpoint after simple shaving. The closeness of hair removal and visible signs of skin irritation can be assessed as additional quantitative parameters from the same images. Discomfort and pain rating by the volunteers complete the set of parameters, which are required to benchmark a new hair removal method or hair-growth-reduction treatment. Image analysis combined with high-resolution imaging techniques is a powerful tool to objectively assess parameters like hair length, hair width, and projection area. To achieve reliable data and to reduce well known image-analysis artifacts, it was important to optimize the technical equipment for use on human skin and to improve image analysis by adaptation of the image-processing procedure to the different skin characteristics of individuals, like skin color, hair color, and skin structure.
 ...
PMID:Use of image analysis techniques for objective quantification of the efficacy of different hair removal methods. 1711 Oct 69

Capsicum-derived ingredients function as skin-conditioning agents--miscellaneous, external analgesics, flavoring agents, or fragrance components in cosmetics. These ingredients are used in 19 cosmetic products at concentrations as high as 5%. Cosmetic-grade material may be extracted using hexane, ethanol, or vegetable oil and contain the full range of phytocompounds that are found in the Capsicum annuum or Capsicum frutescens plant (aka red chiles), including Capsaicin. Aflatoxin and N-nitroso compounds (N-nitrosodimethylamine and N-nitrosopyrrolidine) have been detected as contaminants. The ultraviolet (UV) absorption spectrum for Capsicum Annuum Fruit Extract indicates a small peak at approximately 275 nm, and a gradual increase in absorbance, beginning at approximately 400 nm. Capsicum and paprika are generally recognized as safe by the U.S. Food and Drug Administration for use in food. Hexane, chloroform, and ethyl acetate extracts of Capsicum Frutescens Fruit at 200 mg/kg resulted in death of all mice. In a short-term inhalation toxicity study using rats, no difference was found between vehicle control and a 7% Capsicum Oleoresin solution. In a 4-week feeding study, red chilli (Capsicum annuum) in the diet at concentrations up to 10% was relatively nontoxic in groups of male mice. In an 8-week feeding study using rats, intestinal exfoliation, cytoplasmic fatty vacuolation and centrilobular necrosis of hepatocytes, and aggregation of lymphocytes in the portal areas were seen at 10% Capsicum Frutescens Fruit, but not 2%. Rats fed 0.5 g/kg day-1 crude Capsicum Fruit Extract for 60 days exhibited no significant gross pathology at necropsy, but slight hyperemia of the liver and reddening of the gastric mucosa were observed. Weanling rats fed basal diets supplemented with whole red pepper at concentrations up to 5.0% for up to 8 weeks had no pathology of the large intestines, livers, and kidneys, but destruction of the taste buds and keratinization and erosion of the gastrointestinal (GI) tract were noted in groups fed 0.5% to 5.0% red pepper. The results of 9-and 12-month extension of this study showed normal large intestines and kidneys. In rabbits fed Capsicum Annuum Powder at 5 mg/kg day-1 in the diet daily for 12 months damage to the liver and spleen was noted. A rabbit skin irritation test of Capsicum Annuum Fruit Extract at concentrations ranging from 0.1% to 1.0% produced no irritation, but Capsicum Frutescens Fruit Extract induced concentration-dependent (at 25 to 500 microg/ml) cytotoxicity in a human buccal mucosa fibroblast cell line. An ethanol extract of red chili was mutagenic in Salmonella typhimurium TA98, but not in TA100, or in Escherichia coli. Other genotoxicity assays gave a similar pattern of mixed results. Adenocarcinoma of the abdomen was observed in 7/20 mice fed 100 mg red chilies per day for 12 months; no tumors were seen in control animals. Neoplastic changes in the liver and intestinal tumors were observed in rats fed red chili powder at 80 mg/kg day-1 for 30 days, intestinal and colon tumors were seen in rats fed red chili powder and 1,2-dimethyl hydrazine, but no tumors were observed in controls. In another study in rats, however, red chile pepper in the diet at the same dose decreased the number of tumors seen with 1,2-dimethylhydrazine. Other feeding studies evaluated the effect of red chili peppers on the incidence of stomach tumors produced by N-methyl-N'-nitro-N-nitrosoguanidine, finding that red pepper had a promoting effect. Capsicum Frutescens Fruit Extract promoted the carcinogenic effect of methyl(acetoxymethyl)nitrosamine (carcinogen) or benzene hexachloride (hepatocarcinogen) in inbred male and female Balb/c mice dosed orally (tongue application). Clinical findings include symptoms of cough, sneezing, and runny nose in chili factory workers. Human respiratory responses to Capsicum Oleoresin spray include burning of the throat, wheezing, dry cough, shortness of breath, gagging, gasping, inability to breathe or speak, and, rarely, cyanosis, apnea, and respiratory arrest. A trade name mixture containing 1% to 5% Capsicum Frutescens Fruit Extract induced very slight erythema in 1 of 10 volunteers patch tested for 48 h. Capsicum Frutescens Fruit Extract at 0.025% in a repeated-insult patch test using 103 subjects resulted in no clinically meaningful irritation or allergic contact dermatitis. One epidemiological study indicated that chili pepper consumption may be a strong risk factor for gastric cancer in populations with high intakes of chili pepper; however, other studies did not find this association. Capsaicin functions as an external analgesic, a fragrance ingredient, and as a skin-conditioning agent--miscellaneous in cosmetic products, but is not in current use. Capsaicin is not generally recognized as safe and effective by the U.S. Food and Drug Administration for fever blister and cold sore treatment, but is considered to be safe and effective as an external analgesic counterirritant. Ingested Capsaicin is rapidly absorbed from the stomach and small intestine in animal studies. Subcutaneous injection of Capsaicin in rats resulted in a rise in the blood concentration, reaching a maximum at 5 h; the highest tissue concentrations were in the kidney and lowest in the liver. In vitro percutaneous absorption of Capsaicin has been demonstrated in human, rat, mouse, rabbit, and pig skin. Enhancement of the skin permeation of naproxen (nonsteroidal anti-inflammatory agent) in the presence of Capsaicin has also been demonstrated. Pharmacological and physiological studies demonstrated that Capsaicin, which contains a vanillyl moiety, produces its sensory effects by activating a Ca2 +-permeable ion channel on sensory neurons. Capsaicin is a known activator of vanilloid receptor 1. Capsaicin-induced stimulation of prostaglandin biosynthesis has been shown using bull seminal vesicles and rheumatoid arthritis synoviocytes. Capsaicin inhibits protein synthesis in Vero kidney cells and human neuroblastoma SHSY-5Y cells in vitro, and inhibits growth of E. coli, Pseudomonas solanacearum, and Bacillus subtilis bacterial cultures, but not Saccharomyces cerevisiae. Oral LD50 values as low as 161.2 mg/kg (rats) and 118.8 mg/kg (mice) have been reported for Capsaicin in acute oral toxicity studies, with hemorrhage of the gastric fundus observed in some of the animals that died. Intravenous, intraperitoneal, and subcutaneous LD50 values were lower. In subchronic oral toxicity studies using mice, Capsaicin produced statistically significant differences in the growth rate and liver/body weight increases. Capsaicin is an ocular irritant in mice, rats, and rabbits. Dose-related edema was observed in animals receiving Capsaicin injections into the hindpaw (rats) or application to the ear (mice). In guinea pigs, dinitrochlorobenzene contact dermatitis was enhanced in the presence of Capsaicin, injected subcutaneously, whereas dermal application inhibited sensitization in mice. Immune system effects have been observed in neonatal rats injected subcutaneously with Capsaicin. Capsaicin produced mixed results in S. typhimurium micronucleus and sister-chromatid exchange genotoxicity assays. Positive results for Capsaicin were reported in DNA damage assays. Carcinogenic, cocarcinogenic, anticarcinogenic, antitumorigenic, tumor promotion, and anti-tumor promotion effects of Capsaicin have been reported in animal studies. Except for a significant reduction in crown-rump length in day 18 rats injected subcutaneously with Capsaicin (50 mg/kg) on gestation days 14, 16, 18, or 20, no reproductive or developmental toxicity was noted. In pregnant mice dosed subcutaneously with Capsaicin, depletion of substance P in the spinal cord and peripheral nerves of pregnant females and fetuses was noted. In clinical tests, nerve degeneration of intracutaneous nerve fibers and a decrease in pain sensation induced by heat and mechanical stimuli were evident in subjects injected intradermally with Capsaicin. An increase in mean inspiratory flow was reported for eight normal subjects who inhaled nebulized 10(-7) M Capsaicin. The results of provocative and predictive tests involving human subjects indicated that Capsaicin is a skin irritant. Overall, studies suggested that these ingredients can be irritating at low concentrations. Although the genotoxicity, carcinogenicity, and tumor promotion potential of Capsaicin have been demonstrated, so have opposite effects. Skin irritation and other tumor-promoting effects of Capsaicin appear to be mediated through interaction with the same vanilloid receptor. Given this mechanism of action and the observation that many tumor promoters are irritating to the skin, the Panel considered it likely that a potent tumor promoter may also be a moderate to severe skin irritant. Thus, a limitation on Capsaicin content that would significantly reduce its skin irritation potential is expected to, in effect, lessen any concerns relating to tumor promotion potential. Because Capsaicin enhanced the penetration of an anti-inflammatory agent through human skin, the Panel recommends that care should be exercised in using ingredients that contain Capsaicin in cosmetic products. The Panel advised industry that the total polychlorinated biphenyl (PCB)/pesticide contamination should be limited to not more than 40 ppm, with not more than 10 ppm for any specific residue, and agreed on the following limitations for other impurities: arsenic (3 mg/kg max), heavy metals (0.002% max), and lead (5 mg/kg max). Industry was also advised that aflatoxin should not be present in these ingredients (the Panel adopted < or =15 ppb as corresponding to "negative" aflatoxin content), and that ingredients derived from Capsicum annuum and Capsicum Frutescens Plant species should not be used in products where N-nitroso compounds may be formed. (ABSTRACT TRUNCATED)
 ...
PMID:Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin. 1736 37

Unpleasant odor is a frequent and distressing concern of persons who have wounds, as well as their family members and caregivers. In some instances, standard nursing interventions such as increasing the frequency of dressing changes will not be sufficient to address wound malodor. A review of the literature to summarize research findings about topical metronidazole used to decrease wound odor was conducted. Fifteen (15) studies were identified: seven case reports/series; six descriptive longitudinal studies; and two controlled clinical trials. Metronidazole was used as a 1% solution or, more frequently, as a 0.75% or 0.80% gel. Two reported adverse effects were skin irritation and a burning sensation. Generally, topical metronidazole was reported to result in a reduction or eradication of wound odor, decrease in wound drainage, improvement in wound appearance, decrease in surrounding cellulitis, halting of tissue necrosis, and decrease in pain. Although nurses report success with sprinkling crushed metronidazole pills on wounds, no published reports of this method of topical application are available. Topical metronidazole may be considered as an option for the management of malodorous wounds and additional randomized controlled trials with adequate sample sizes and comparison to products noted to decrease odor are warranted. While topical metronidazole for the treatment of malodorous wounds presently is off-label, perhaps such studies will result in the addition of malodorous wounds to the list of its indications.
 ...
PMID:Topical metronidazole for the treatment of wound odor: a review of the literature. 1838 45

Microneedle arrays are promising devices for the delivery of drugs and vaccines into or the skin. However, little is known about the safety of the microneedles. In this study we obtained insight in the ability of microneedles to disrupt the skin barrier, which was evaluated by transepidermal water loss (TEWL). We also determined the safety in terms of skin irritation (skin redness and blood flow) and pain sensation. We applied microneedle arrays varying in length and shape on the ventral forearms of 18 human volunteers. An effect of needle length was observed, as TEWL and redness values after treatment with solid microneedle arrays of 400 microm were significantly increased compared to 200 microm. The blood flow showed a similar trend. Needle design also had an effect. Assembled microneedle arrays induced higher TEWL values than the solid microneedle arrays, while resulting in less skin irritation. However, for all microneedles the irritation was minimal and lasted less than 2h. In conclusion, the microneedle arrays used in this study are able to overcome the barrier function of the skin in human volunteers, are painless and cause only minimal irritation. This opens the opportunity for dermal and transdermal delivery of drugs and vaccines.
 ...
PMID:In vivo assessment of safety of microneedle arrays in human skin. 1865 10

The majority of midclavicular fractures are treated conservatively. Fractures that require internal fixation are treated by plate osteosynthesis as the standard procedure. Elastic stable intramedullary nailing is an increasingly popular alternative for the internal fixation of displaced midclavicular fractures. In a three-year period, 15 fractures of the clavicle were treated by elastic intramedullary nailing. Fracture healing, clinical outcome and complications were assessed. Mean follow-up time was one year All fractures healed clinically and radiologically. Non-union or infections were not observed. Functional results according to the Constant score were excellent. Complications consisted of skin irritation in four cases. One acromioclavicular joint separation was observed postoperatively. Elastic stable intramedullary nailing of displaced midclavicular fractures is a minimally invasive technique with excellent functional results and early pain relief.
 ...
PMID:Elastic intramedullary nailing of midclavicular fractures. 1880 95

Persistent pain following unilateral total hip replacement was approached with multiple electrical modalities. lontophoresis, with several ions for specific physiological effects, was utilized successfully. When skin irritation was encountered, high frequency sine wave, i.e., 1 kilohertz, was substituted because of its nonirritating, deep penetration qualities. Ultrasound was also utilized as an adjunct in the attempt to introduce the chemicals previously introduced by iontophoresis by way of the phonophoretic process. TENS was applied at home between office visits to maintain pain control but was not, apparently, involved in the overall rehabilitative process of the pathological conditions, since no lasting analgesic effects were noted. Traditional electrical stimulation techniques were added to the program when specific muscular weakness was noted, using surged sine wave at 1 kilohertz to the affected musculature. The favorable results of this multiphasic approach are clearly demonstrated in the relatively pain-free, functional activities of the patient. J Orthop Sports Phys Ther 1981;2(4):180-183.
 ...
PMID:Electrotherapeutic Approach to Postoperative Pain following Total Hip Replacement: A Case Study. 1881 Jan 50


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>