Grapefruit Benefits and Uses

The grapefruit (Citrus paradisi Macfad) is a large orange-like fruit that belongs to the citrus family. Fruit grows in varieties of pink/red, yellow, white or ruby color. The pink or red varieties are higher in vitamin content.

Grapefruit Benefits

Fresh squeezed grapefruit juice contains vitamin C. Vitamin-C is a potent antioxidant and helps the body develop resistance against infectious agents and scavenge harmful free radicals. The fruit contains very good levels of vitamin-A, and flavonoid antioxidants such as naringenin, and naringin. Vitamin A intake supports your immune system, helps maintain healthy retinas and acts as an antioxidant in body. Grapefruit is a good source of potassium. Potassium, is one of several electrolytes that sustain fluid levels and electrical activity in your body. Insufficient potassium can result in an irregular heartbeat, known as arrhythmia. Potassium is an important component of cell and body fluids, helps controlling heart rate and blood pressure through countering sodium effects.

GrapefruitThe vitamin C and the antioxidant properties protect the skin from environmental hazards. It also stimulates the production of skin collagen that brings smoothness and elasticity to the skin. “Grapefruit is loaded with vitamin C, a mild acid, which helps fade spots by reducing excess production of skin pigment,” says Jessica Wu, MD, a Los Angeles–based dermatologist.

Grapefruit is a source of fiber. This fruit contains high level of pectin which acts as a bulk laxative and helps to protect the colon mucous membrane by decreasing exposure to toxic substance in the colon. Fiber is necessary to promote regular bowel movements and to prevent constipation.

Grapefruit juice helps increase your urinary pH value, which significantly lowers risk of calcium oxalate stones forming in the kidney. A study reported in the “British Journal of Nutrition” demonstrated that drinking 2-4 cups daily of grapefruit or orange juice reduced the risk of developing kidney stones.

Red varieties of grapefruits are particularly rich in the most strong flavonoid antioxidant, lycopene. This carotenoid is believed to have potent antioxidant effects with some studies showing a reduced risk of cancer, cardiovascular disease and macular degeneration. The optimum dosage for lycopene has not been established, but the amount found useful in studies usually fell in the range of 4 to 8 mg daily. In a study reported in the March 2005 edition of International Journal of Cancer, scientists found that prostate cancer risk declined with increased consumption of lycopene. Lycopene has shown promise for leukoplakia. In a clinical trials, 58 participants with oral leukoplakia received either 8 mg oral lycopene daily, 4 mg daily, or placebo capsules for 3 months. Subjects were then followed for an additional two months. The results showed  that lycopene in either dose was more effective than placebo for reducing signs and symptoms of leukoplakia, and that 8 mg daily was more effective than 4 mg.

Naringenin, a flavonoid concentrated in grapefruit, helps repair damaged DNA in human prostate cancer cells. A study that was reported in the “Journal of Nutritional Biochemistry” shows that grapefruits help repair damaged DNA in human prostate cancer cells. A group of phytonutrients in grapefruits called limonoids help prevent tumors by promoting an enzyme that causes the liver to expel more toxins from the body. In animal-based studies and lab tests with human cells, limonoids have been shown to help fight cancers of the mouth, skin, lung, breast, stomach and colon. Limonoids help control the activity of genes in cancer cells, activating genes that promote cancer cell death, according to a research reported in the Journal of Biological Chemistry in 2011. Research indicate that drinking grapefruit juice everyday helps reduce the activities of enzymes that can activate cancer triggering chemicals found in cigarette smoke. In humans, drinking three 6-ounce glasses of grapefruit juice a day was shown to reduce the activity of an enzyme that activates cancer-causing chemicals found in tobacco smoke.

Pomegranate Benefits for Health

The pomegranate is a member of the Punicaceae family. The fruit is comprised of peel, seeds, and aril. An average pomegranate contains approximately 600 juicy seeds, which are encapsulated in white pith. Pomegranates are high in polyphenols, including flavonoids and tannins.

Pomegranate Benefits

Pomegranate ( Punica granatum L.) contains a variety of chemicals that might have antioxidant properties. Pomegranate  is high in 3 different types of polyphenols, a strong form of antioxidants. The three types – anthocyanins, ellagic acid, tannins – are present in many fruits, but fresh pomegranate juice contains especially high levels of all three. Preliminary studies indicate that pomegranate juice may contain nearly three times the total antioxidant ability compared to the same quantity of  red wine or green tea. Some research show that chemicals in pomegranate juice might slow the progression of atherosclerosis and possibly fight cancer cells.

Cardiovascular Disease

PomegranatePomegranate juice contributes curing and preventing cardiovascular disease. Studies demonstrate that the different and high antioxidant content decreases inflammation and thickening of the artery walls. Researchers attribute heart healthy benefits to polyphenols, including anthocyanins, which are plant pigments that give the pomegranate its red hue. A study reported in “Proceedings of the National Academy of Sciences” found that pomegranate juice combats hardening of the arteries and related diseases like heart attacks and strokes. Researchers in Israel have shown that drinking a daily glass of the fruit’s juice can reduce the risk of cardiovascular disease. “Pomegranate juice contains the highest antioxidant capacity compared to other juices, green tea and red wine ,” said Professor Michael Aviram, who led the team.

Pomegranate juice may improve blood flow to the heart in individuals with ischemic coronary heart disease. In a clinical trial of 45 patients with coronary heart disease and myocardial ischemia, participants who drank approximately 8 fluid ounces of pomegranate juice daily for 3 months had less ischemia during a stress test. Study participants who did not drink the juice, meanwhile, had evidence of more stress-induced ischemia. New research evaluated heart patients with severe carotid artery blockages. Pomegranate was shown to have strong anti-atherogenic properties in healthy humans and in mice with plaque buildup. Participants were given an ounce of pomegranate juice each day for a year. Not only did study participants’ blood pressure lower by over 12%, but there was a 30 % decline  in atherosclerotic plaque. Participants who did not take the pomegranate juice saw their atherosclerotic plaque increase by 9%. In other studies, powerful antioxidant compounds found in pomegranates have shown to reduce platelet aggregation and lower blood pressure, factors that prevent both heart attacks and strokes.


Pomegranate juice and extract, inhibit the proliferation of various prostate cancercell linesin vitro and induce apoptoticcell death in a dose-dependent manner. Pomegranate juice may slow prostate cancer growth. The juice appeared to suppress the growth of cancer cells and the increase in cancer cell death in laboratory experiments, according to research from UCLA. In a study of men who had undergone therapy for prostate cancer, 8 ounces of pomegranate juice every day kept their Prostate-specific antigen (PSA) levels stable thereby reducing the need for more treatment such as chemotherapy or hormone therapy. The ellagitannins found in pomegranates juice have the ability to prevent cancer cells from becoming mobile. Researches also show reduced blood supply to tumors which prevents cancer cells from obtaining nutrients. Mice that had been inoculated with human prostate cancer cells received a four week therapy of pomegranate  extract. The results demonstrated a significant decrease in tumor size and tumor vessel density.

The insulin-like growth factor (IGF) system has been implicated in prostate cancer. A study reported in 2010 investigated the effects of a POMx  (10 µg/mL concentration of pomegranate extract prepared from skin and arils minus seeds) on the IGF system. Treating LAPC4 prostate cancer cells with POMx resulted in cell growth inhibition and apoptosis.  Pomegranate may help prevent and slow the growth of some types of breast cancer. In the lab, pomegranate extracts inhibited human breast cancer cells’ ability to proliferate and spread to other areas and induced programmed cell death. Pomegranate showed efficacy against both estrogen-dependent and estrogen-independent breast cancer cells. Pomegranate may also help reduce the risk of colon. Pomegranate extract reduced the number and size of experimentally induced colon tumors in animal subjects. In the lab, pomegranate juice inhibited the proliferation and increased programmed cell death of human colon cancer cells.


Studies have shown that pomegranate extract have anti-inflammatory properties that stop the destruction of joints caused by osteoarthritis. Researchers at “Case Western Reserve University” have reported that tissue cultures of human cartilage cells respond to pomegranate extract. In laboratory tests, the pomegranate extract; 1-Cut levels of an inflammatory chemical called IL-1b (interleukin-1b). 2-Stopped enzymes that erode cartilage.  Scientists said their findings “indicate the pomegranate fruit extract or compounds derived from it may inhibit cartilage degradation in osteoarthritis and may also be a useful nutritive supplement for maintaining joint integrity and function.

Erectile Dysfunction and Fertility

Pomegranate juice may help increase sexual performance and fertility. Men and women who drank a glass a day for a fortnight were found to have increased levels of the sex hormone testosterone. A study on 58 participants aged between 21 and 64 found significantly increased testosterone levels in both sexes at the end of the two week experiment. A glass of pomegranate juice every day may help manage erectile dysfunction. Writing in the International Journal of Impotence Research, researchers from The Male Clinic, Beverly Hills, and University of California, report that 47% of participants reported erections improvements as a result of pomegranate juice, compared to only 32%  in the placebo group.

A animal-based study has been conducted on 28 male rats to examine the sperm production after giving them pomegranate juice. The study has successfully showed that pomegranate juice significantly enhanced sperm count of those rates. Compared with the mice drinking only water, the mice drinking concentrated pomegranate juice experienced a 48.5% decrease in their blood levels of malondialdehyde (a reactive carbonyl compound and a major end product of lipid oxidation), and a 63.5%  decrease in the levels of the chemical in their sperm.

Walnut Benefits and Uses

Walnut is an edible seed of the tree nut Juglans regia. These nutrient contain high levels of polyphenols, phytochemicals that have antioxidant effects. Also, walnuts are an excellent source of a proteins, fiber, and manganese, magnesium and copper.

Walnut Benefits

Researchers from Pennsylvania told the American Chemical Society that walnuts contain the highest amount of antioxidants compared to other nuts. Antioxidants protect cells against damage caused by harmful molecules known as free radicals. The researchers said that all nuts have good nutritional qualities but walnuts are healthier than peanuts, almonds, pistachios and pecans. Dr Joe Vinson, from the University of Scranton in Pennsylvania, tested the antioxidant levels of nine different types of nuts and discovered that a handful of walnuts contained twice as many antioxidants as a handful of any other commonly eaten nut. “Twenty-eight grams of walnuts have more antioxidants than the sum of what the average person gets from fruits and vegetables,” he says.

Heart Disease

WalnutsNuts, like almonds, hazel nuts, Brazil nuts, peanuts, walnuts and cashews can all play a role in reducing the risk of heart disease, according to a Harvard review. Walnuts are a good source of the healthy fat alpha linolenic acid. (One-quarter cup of walnuts provides all the alpha linolenic acid you need in a day). New researches have associated a higher intake of alpha linolenic acid to a reduced risk of heart disease and heart attack in men. One study looked at nuts rich in alpha linolenic acid (ALA), like walnuts, and found that they had a heart-protective effect during times of acute stress. A meta-analysis reported in the new ssue of the “American Journal of Clinical Nutrition” evaluates how the plant-based omega-3 fatty acid ALA offers protective effects on cardiovascular diseases. The study found ALA to be linked  with a lower risk of cardiovascular diseases, especially coronary heart disease death.

Besides omega-3 fatty acids that prevents erratic heart rhythms and regulate plaque formation in blood vessels, the amino acid arginine in walnuts improves the elasticity of blood vessels. Overweight people can help protect themselves from heart disease and diabetes by adding walnuts to their diet. A group of at-risk adults who were put on a walnut-enriched diet saw improved endothelial function, which impacts inflammation and controls blood pressure, according to study out of Yale University. Due to the strength of evidence supporting cardiovascular health, the Food and Drug Administration (FDA) approved a qualified health claim for walnuts in March 2004.


Numerous substances in walnuts, such as gamma tocopherol, polyphenols, and phytosterols, may offer protection against cancer development. In a study, reported in “Nutrition and Cancer“, studied whether consumption of walnuts could affect growth of human breast cancer tumors (MDA-MB 231) implanted into mice. After 35 days, the breast cancer tumors of the walnut fed mice were significantly less. Recent research from the School of Medicine at The University of Texas Health Science Center San Antonio demonstrates that eating a modest amount of walnuts can protect against prostate cancer. Scientists  at the UT Health Science Center injected immune-deficient mice with human prostate cancer cells. Three of 16 mice eating the walnut-enriched diet developed prostate tumors, compared with 14 of 32 mice on the non-walnut control diet.”We found the results to be stunning because there were so few tumors in animals consuming the walnuts and these tumors grew much more slowly than in the other animals,” disclosed study senior author Russel Reiter.


Since there’s a high concentration of omega-3 fatty acids in walnuts, they’re important for brain health. Insufficient omega 3 intake has been associated to depression and decline in cognitive function. A study done at “Purdue University” demonstrated that children with a lower concentration of omega-3 fatty acids have a higher risk of hyperactivity, learning disorders, and behavioral problems. Although research has not found a way to ward off dementia cognitive decline may be preventable. Consuming specific foods, being physically active, and engaging in social activities may help maintain and increase cognitive health. Beyond protecting against age-associated problems, a British Journal of Nutrition animal study found that walnuts may improve working memory, problem-solving and motor function. The combination of antioxidants and alpha linolenic acid in walnuts may provide antiamyloidogenic, anti-inflammatory and antioxidative effects, thereby protecting brain cells. An in vitro study using walnut extract found that it counteracted oxidative stress and cell death caused by amyloid beta-protein, a major component of amyloid deposits and senile plaques in the brains of people with Alzheimer’s disease.


A Yale study reported in “Diabetes Care” finds walnuts improve blood flow in adults with type 2 diabetes. Endothelial function significantly improved after consumption of the walnut-enriched diet compared to the diet without walnuts. The scientists concluded that a walnut-enriched diet may improve endothelium-dependent vasodilatation in patients with type 2 diabetes, thus reducing overall cardiac risk. New research reported online by the “Journal of Nutrition”, found an inverse correlation between walnut consumption and risk of type 2 diabetes in two large prospective cohorts of US women: the Nurses’ Health Study (NHS) and NHS II. Scientists followed approximately 138,000 women over a 10-year period and found that those who ate two or more 1-oz servings of walnuts per week were 24% less likely to develop diabetes compared with those who ate fewer or no walnuts.

Male Fertility

Walnuts have been associated to a positive effect on sperm development. Eating around two handfuls of walnuts a day ameliorates sperm health in young men, a study in the journal “Biology of Reproduction” suggests. In this study, 117 healthy men aged 21 to 35 were randomized either to continue eating their usual diet or adding 2.6 ounces of walnuts to their usual diet. Sperm shape, movement and vitality improved in men who added walnuts to their diet over twelve weeks. The control group experienced no changes.

Alfalfa uses and Benefits

Alfalfa (Medicago sativa), also known as lucerne, is a member of the pea family. Sometimes called Buffalo Herb, Alfalfa means “Father of all Foods”. Alfalfa leaf contains essential vitamins including of B-vitamins, A, D, E and K. Also alfalfa is a source of iron, magnesium, calcium, potassium and phosphorous.

Alfalfa Uses

Traditional Chinese Medicine used young alfalfa leaves to treat disorders of the digestive tract.  The Ayurvedic physicians has used alfalfa leaf to relieve water retention, arthritis, and ulcers. In the 19-th century American physicians recommended alfalfa as a tonic for digestive dysfunctions, dyspepsia, lack of appetite, and anemia.

The vitamin K in alfalfa promotes healthy blood clotting, which is necessary for wound healing. Vitamin K plays major role in blood clotting process, is essential for prothrombin formation in the liver, thus alfalfa helps to prevent bleeding, and normalizes blood coagulability during hemorrhaging by strengthening the blood vessel walls and increasing the prothrombin production.

Alfalfa plant is a good source of chlorophyll. Chlorophyll is actually responsible for the green pigmentation in plants. Plants use chlorophyll to trap light needed for photosynthesis. The chlorophyll molecule is very similar in structure to the haemoglobin molecule. The difference between them is that the heme molecule contains the element iron at its centre, whereas the chlorophyll molecule, also an oxygen-carrier contains magnesium. Chlorophyll enhances the capability of nutrients that build iron in the body and so it develops the production of red blood cells. Also, because it contains magnesium, enhances the transportation of oxygen to the tissues, develops circulation and oxygen supply.

Anemia happens when your blood does not have enough red blood cells to properly carry oxygen to organs and tissues. Alfalfa, dandelion root or leaf, burdock and yellowdock have traditionally been used to fortify and cleanse the blood. Also, a study reported in 2012 by the “Institute of Soil Science and Plant Cultivation“, shows that alfalfa extract enriched with vitamin C supports the human body in fighting malnutrition, ischemic diseases and problems of the digestive tract.

Alfalfa may offer liver-protective effects according to a study reported in the 2012 edition of the American Journal of Chinese Medicine. In the animal-based study, supplement with alfalfa extract for 3 weeks prevented elevations in liver enzymes and reduced oxidative stress in response to a chemical irritant. The present study was performed to determine whether lyophilized aqueous extract of alfalfa, could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. Results shows that the alfalfa extract possesses hepatoprotective and antioxidative stress effects possibly through its antioxidant phytochemical constituents and substantiate its use in various liver disorders as a hepatoprotector.

Alfalfa appears to lower blood glucose levels in animals. In a study, streptozotocin diabetic mice fed alfalfa experienced reduced hyperglycemia when compared with normal mice.

Alfalfa, has traditionally been used for women with menopausal symptoms. Alfalfa leaves contain flavones, isoflavones, coumarin  and sterols derivatives. The isoflavones may cause the estrogen-like effects seen in animal-based studies. Supplementing with alfalfa  and sage leaf (Salvia officinalis) extract completely eliminated hot flushes and night sweats in 20 of 30 women in one clinical trial. Sage leaf and alfalfa seem to have a central slight antidopaminergic action without adverse effects and appear to be an useful combination in the therapy of menopausal symptoms.

Borage Uses and Benefits

Borage (Borago officinalis ) or starflower, is a plant with bright blue, star-shaped flowers. Borage seed oil is a cold-pressed extract from the seed of the borage plant. Gamma-linolenic acid (GLA) is an essential fatty acid that’s important for maintaining a joint’s cell structure and function. Borage oil contains very high levels of two types of polyunsaturated omega-6 essential fatty acids, 20–26% GLA and LA (linolenic acid). Other sources of GLA include black currant seed oil and evening primrose oil.

What is Borage Oil Good For?

Borage oil, are natural source of a fatty acid called GLA (gamma linolenic acid ). This is a “good” fatty acid that is converted in the body to prostaglandin, which has known anti-inflammatory, blood-thinning, and blood vessel dilatory effects. Gamma linolenic acid inhibits leukotriene synthesis to provide treatment in rheumatologic diseases. Therefore, borage seed oil may have anti-inflammatory and anti-thromboti cproperties and benefit individuals at risk of different inflammatory disorders such as arthritis, atopic eczema, and respiratory inflammation. Gamma linolenic acid can enhance cAMP levels which suppresses the synthesis of tumor necrosis factor-alpha – an inflammatory mediator linked to rheumatoid arthritis. Various experiments has underlined its possible use in relieving the pain and swelling of rheumatoid arthritis, as well as other inflammatory disorders such as Sjogren’s syndrome, and ulcerative colitis. Clinical studies have been conducted with borage oil or purified GLA in several diseases.

Rheumatoid Arthritis

Borage OilScientists at the “University of Pennsylvania” found that supplement with borage oil resulted in a important reduction in the swelling of affected arthritic joints. The use of borage oil allowed patients to reduce their intake of mainstream NSAIDS, therefore minimizing the adverse effects related with these drugs. Also, animal-based studies using borage oil indicated that the GLA content  protects the lining of the stomach against the effects of NSAIDS and aspirin. GLA may help reduce pain, stiffness, and swelling. One study found that participants with RA (rheumatoid arthritis) who took 2.8 g of gamma linolenic acid for 6 months reduced pain and swelling and improved their grip strength. 64% of those on borage oil demonstrated improvement in joint tenderness and morning stiffness, compared to just 21% of those on placebo treatment.  A randomized controlled study investigated the use of borage oil in 37 participants with RA and active synovitis. After 24 weeks, the group that received 1.4 g of GLA daily had a important decline in the number of tender joints and swollen joints. In another study, 1.1 g of borage  oil was given to seven patients with rheumatoid arthritis for 12 weeks. Six of the seven patients with RA reported relief of their symptoms.


Prostaglandin 1 (PG1) shows a strong anti-inflammatory propertyon the skin and also is effective in regulating water loss and protecting skin from injury and damage. New researches demonstrate that borage oil taken orally increases PG1 levels in the skin and suppresses chronic inflammation. Findings from animal studies shows that skin disorders linked with fatty acid imbalances can be corrected through dietary inclusion of borage oil. In a study was conducted to know the effects of borage oil containing skin creams on dry and damaged skin of 24 healthy participants with dry and scaly skin. It demonstrated that borage oil is able to restore the moisture and softness of dry skin. A small trial in healthy elderly participants reported improved cutaneous barrier function after two months of borage oil supplementation. Supplements containing borage or flaxseed oil may protect skin against reddening and ameliorate skin health from within, suggests study  from Germany and France. The scientists, recruited 45 non-smoking, healthy women between the ages of 18 and 65 and randomly assigned them to one of three groups. Two groups received daily supplements of oil borage or flaxseed oil (2.2 g of total fatty acids), while a third received medium-chain fatty acids as the placebo. Following nicotinate therapy, the scientists noted a important decrease in reddening of the skin in the flaxseed and borage oil groups of 45 and 35%, respectively, compared to baseline values. No differences were recorded in the placebo group. Scientists at the University of Italy conducted a study that documented the important effects that borage oil can have on people with atopic eczema. Scientists have observed that the effects of GLA may continue several weeks or months after stopping the supplement. Oral dose of 548 mg/day, for twelve weeks.


The rich stores of essential fatty acids have useful effects on nails, hair and scalp. Borage oil heals common scalp disorders such as hair loss, dandruff and folliculitis because of its anti-inflammatory properties. A study reported the British Journal of Nutrition demonstrated that flaxseed and borage oil reduced redness and flaky skin in 45 women, ages 18-65.

Periodontitis / Gingivitis

The use of borage oil supplement, a source of the n-6 PUFA, GLA, can have useful effects on periodontal inflammation. The anti-inflammatory activities of both n-3 and n-6 polyunsaturated fatty acids (PUFA) have been showed in vitro and in several disease states. The effect of n-3 PUFA supplement has been documented in animal models of periodontal inflammation and a trend towards reduced inflammation has been seen in human experimental gingivitis. Borage oil reduce  gingivitis and ameliorate gum health in individuals with inflammation in the areas of the mouth around the teeth (periodontitis), according to a new study in Prostaglandins, Leukotrienes and Essential Fatty Acids. In this study, 24 participants with periodontitis were randomly assigned to receive one of the following 4 therapies; : 1,000 mg of borage oil 3 times per day, 1,000 mg of fish oil 3 imes per day, 500 mg each of borage and fish oils 3 times per day, or placebo. At the end of 12 weeks, there was a important decrease in gingivitis and depth of pockets around teeth in the borage group.

Acute Respiratory Distress Syndrome

There is some findings that borage oil, when taken in combination with EPA (eicosapentaenoic acid), might reduce the number of days spent in the intensive care unit (ICU) and the length of time a breathing machine is needed by people with acute respiratory distress syndrome. Acute respiratory distress syndrome (ARDS) is a medical emergency that leads to lung tissue injury and fluid build-up in the lungs. Eicosapentaenoic acid (EPA) and gamma linolenic acid (GLA)  work together to reverse the lipid balance and reduce the extent of damage in the pulmonary tissue. Fish Oil, a rich source of EPA, may reduce the body’s production of arachidonic acid, which facilitates the production of potent pro-inflammatory metabolic components. Borage seed oil contains a high content of GLA that is known to act as a substrate for the production of powerful anti-inflammatory eicosanoids on a cellular level in the human body. James Gadek of Ohio State University Medical Center and Michael J. Murray of the Mayo Clinic, have reported that borage seed oil, in a mixture with fish oil and antioxidants, can significantly improve the condition or even the chances of survival in patients with ARDS.

Blood Pressure

Clinical trials of borage oil indicate it to be beneficial in reducing the reactivity of heart and blood vessels to stress.  In a 1996 study reported in the “Journal of Human Hypertension“, participants who received 1 g of GLA per day for four weeks had much lower blood pressure than patients in the placebo group.


Borage oil has been shown to alleviate the symptoms of pre-menstrual syndrome (PMS) and menopause. Pre-menstrual syndrome is thought to affect approximately 90%  of women at some point in their lives. GLA seems useful in some women as a remedy to relieve the symptoms of PMS such as abdominal distension, breast discomfort, irritability and depression. GLA is a fatty acid found in vegetable oils. By interfering with the production of inflammatory substances called prostaglandins which are released during menstruation, the GLA in borage oil may help alleviate related cramping and pain.