It is made of the hydrophilic polymer which helps to grow new tissue by creating a humid environment in the wound site. Hydrogel will reduce the pain by creating a cold surface on the wound. Hydrogel dressing can be easily and removed from the wound site without feeling sore [19].

Brent et al. (1998) has compared the effectiveness of hydrogel dressing in the experimental group with lanolin and breast protector in the control group. Mothers in both groups were taught the correct breastfeeding methods. Mothers in the experimental group used hydrogel dressing immediately after massaging the nipple with their milk and before milk drying, but mothers in the control group were asked to use lanolin and breast protection after milk drying. They have examined the pain severity and wound size in the most 3 times in 10 days or until the symptoms were removed. Standard 4-degree questionnaires have been used to measure the wound healing. Redness, edema, ecchymosis and desquamation, as well as secretions criteria examined using this questionnaire. The scaling with 11 degrees was used to measure the pain in which 0=not feeling the pain and 11=severe pain. The fissure severity mean was 4.5 and 5.78 before treatment in the control and experimental group, respectively, and at the following up time of treatment it was respectively 2.33 and 4.87 in the control and experimental group. According to the results, the recovery rate was significantly more in the lanolin and the breast protector group than the hydrogel group. Mothers in the lanolin and breast protector have experienced significantly lower pain during breastfeeding than the hydrogel group (p <0.05) [20].

Centuori et al. (1999) have studied the effect of midwifery standard care on subjects that received no treatment and they just received the usual care of midwifery, including using the ointment or the spray in the control group (ointment ingredients including albumin, glycerin, casein, paraffin oil, lanolin, gel, petroleum, zinc oxide, sodium hydride and potassium, and spray components including cholesterol 0.15 g and neomycin sulfate 0.15 g in 30 ml). The examination was done at the time of discharge, 2 weeks and 3 months after the intervention and through observing and measuring the fissure site. The results suggested that the nipple fissure and breastfeeding duration are not affected by ointment, but teaching the correct breastfeeding methods and supporting the mother are more effective [21].

The lanolin will prevent the wounds by creating a humid skin and heal the wounds by increasing the epithelial re-growth rate. Ester is the active ingredient of lanolin. Esters have the wound healing property in a humid environment as well as the anti-inflammatory, anti-bacterial, skin protector and healing barrier. When the breast tissue is injured, then the chemicals like Histamine and bradykinin are released at the injury site and cause pain. The lanolin will increase the healing by maintaining the injured tissue moisture and reduces the amount and duration of the exposure to these chemicals and thus relieves the pain [22].

In Jackson et al (2016) study the research units were randomly placed in one of these 2 groups: the lanolin or the standard care (breastfeeding advice, mother breastfeeding method assessment, hot or cold compress usage, Ibuprofen or acetaminophen and nipple drying by air exposure). Both groups were taught the correct breastfeeding method. Mothers in the experimental group were asked to use a little amount of the lanolin on their nipple and repeat this until there is no pain or until the end of the duration. The control group received the routine care. The NRS tool was used to measure the pain severity and in order to measure the pain quality we have used the McGill questionnaire. A research assistant who was not aware of the treatment type made a phone call to the mothers in the 4th and 7th days after the intervention and asked them about the nipple pain. The research assistant collected the data in the 4th and 7th days after the intervention and the 4th and 12th weeks after delivery. The results indicated that lanolin had no effect on the nipple pain [10].

Dennis et al (2012) have shown that All-Purpose Nipple Ointment (APNO) ointment containing an antibacterial agent (15 g of 2% w/w Mupirocin), an antifungal agent (15 g of 2% w/w miconazole ) and a hydrocortisone (15 g of 0.1% w/w omeprazole)) and the lanolin were prescribed for the intervention and the control group, respectively. The pharmacists have assigned the APNO and lanolin in similar tubes. The research units were asked to dry the breast after each breastfeeding and use the drug and rub it around the areola and not to clean it till the next breastfeeding while not using any other drugs during the research for the nipple pain relief. Both groups were taught the correct breastfeeding methods. The McGill Pain Questionnaire (including 15 items, emotional and mental aspects of pain) and the nipple assessment questionnaire were used in this study. The pain severity and the nipple soreness were checked through a phone call by the researcher 1 and 12 weeks after the intervention. There was no significant statistical difference between the two groups in the mean score of the pain and healing duration of the first week after the intervention. (p = 0.97). The results showed that the common ointment to heal the nipple fissure was not superior to lanolin [23].

Phototherapy, in the range of 630 to 1000 nm, is an effective tool in regeneration of tissue that will increase the wound healing rate through increasing the proliferation of fibroblasts, collagen synthesis and its progenitor as well as stimulate the angiogenesis and production of growth factor [24, 25].

Chaves et al (2012) has shown the effects of phototherapy on the nipple fissure healing rate on 16 breastfeeding women suffered from the fissure. The women were randomly divided into 2 groups. Both groups were taught the correct breastfeeding methods and the nipple care. Phototherapy and placebo phototherapy were prescribed for the intervention and control group twice a week in 8 sessions, respectively. The nipple was photographed before intervention and during 8 sessions of treatment. The images obtained by Quantikov software were examined. The pain severity was measured in all treatment sessions before and after phototherapy using the PI-NRS 11-degrees tool. The PGIC standard tool was used to determine the pain status and the participants recorded their pain status at the end of each session. The results suggested that phototherapy reduces the pain severity and the nipple wound size so that the nipple fissure of research units in the experimental group was fully healed after 4 sessions of treatment while same healing was achieved in the control group at the eighth session. Although, the pain severity was reduced in both groups, but this reduction was only significant in the experimental group. (p=0.001). The participants in the phototherapy group reported their status highly healed at the end of the treatment [25].

These lasers are also named as bio-stimulating or low intensity lasers. Wound healing, stimulation of cellular processes, pain reduction, local blood flow acceleration and attenuation of inflammation has been mentioned as advantages of this therapeutic approach [26]. The followings could be listed as the biological effects of laser therapy:

1. Increasing the blood flow rate through vascular dilatation
2. Changing the hydrostatic pressure in capillaries
3. Stimulating the immune processes,
4. Stimulating the fibroblasts growing,
5. Increasing the collagen synthesis,
6. Generating new vessels and capillaries and
7. Decreasing the prostaglandin levels which lead to increase wound healing rate and the pain and inflammation reduction [27].

Coca et al (2016) has carried out an investigation entitling the effects of low level laser on the nipple pain severity in breastfeeding women in Sao Paula. The experimental group has been treated using low level laser, in this way that a 40-milliwatt laser beam was radiated into three consecutive points (center, left and right) on the nipple wound, but the red light, lacking health benefits and strength, was used for the control group. In this study, the patients and the two applier nurses were blinded and unaware of the treatment types. The treatment was done in three sessions (0, 24 and 48 hours after fissure detection) for both groups. VAS scale, including a non-grading 10 cm line, was used to measure the mothers’ nipple pain level during breastfeeding. Mothers marked their pain level before and after each session. The pain severity mean before the intervention in both groups was 6.4 cm at the first session, while this amount had a statistically significant decrease of 1.3 cm after laser radiation in the experimental group (p = 0.05). The mean difference of the pain severity in the experimental group was 2 cm after the laser radiation at the second session that showed a statistically significant difference (p = 0.016), but this difference was not significant in the control group (P = 0.630). There was no statistically significant difference at the third session in the pain mean severity in the experimental group before and after treatment which was mainly caused because of mothers’ discharge of the hospital and the sample drop. The results of this study have suggested that the pain during the breastfeeding is greatly reduced using the low intensity laser therapy and it can be a good option for immediate relief of the nipple pain [28].

For centuries, silver has been known as a natural agent with anti-bacterial and remedy properties. Its particles destroy the bacterial respiratory system in the form of interacting with the bacterial respiratory chain enzymes after sticking to the surface of the cell membrane of the bacteria. It does not only stick to the cell membrane surface, but also penetrates the cells and then disables its enzymes and will kill the bacteria by producing the hydrogen peroxide. The silver cap not only prevents the entrance of microorganisms to the wound site, but also protects the nipple against trauma and attrition as a cover. The indirect healing effect of the silver is attributed to create a humid environment at the wound surface and eventually the duplication and migration of the epithelial cells in the affected site [29].

Marrazzu et al (2015) has investigated the effect of the silver cap on the nipple pain heal and reduction. After the participants were randomly grouped in two, the intervention and control group, then were recommended a standard care (personal hygiene protection and nipple care) along with rubbing the breast milk after each breastfeeding around the fissure. Both groups were taught the correct breastfeeding methods. The severity score was used to examine the fissure which measures its severity based on the sum of the score of the three main fissure variables (1. Pain: Numerical rating scale (NRS) is an 11­degree tool that is a 10 cm line on which 0 and 10 are determined for the beginning and the end to indicate the severity of the patient’s pain. 0= no pain, 10= the most severe pain. 2. Bleeding: to measure the amount of bleeding the scoring is as follows: 0= non-bleeding during breastfeeding, 1–3= sometimes bleeding during breastfeeding, 4–6= at least one case of bleeding during the day, 7–10= bleeding in each breastfeeding time. 3. The fissure size was measured using a millimeter ruler and its largest was 10 mm. In this scale 0= no fissure, 1–10= small, 11–20=moderate, more than 21= sever and we have only studied the women who were included in the moderate or severe groups. Duration of the study was 15 days and the examination was done in the 0, 2nd, 7th and 15th days. Based on the results the silver cap is more effective to reduce and heal the nipple pain than the standard care, so that in the 7th day in the experimental group 69% and in the control group 21% had no pain. The fissure healing in 7th and 15th days was 69% and 31%, 50% and 36% in the intervention and control group, respectively [30].

The Polyethylene protector will help the wound to heal by creating a humid environment, protect wound from mechanical sores and prevent the bacterial invasion. Zimmer et al (1995) has studied the effect of the polyethylene film on the nipple fissure of 50 breastfeeding women. A polyethylene protector was randomly put for 7 days on a nipple (3-inch polyethylene film) and the other nipple was treated without as the control group. This polyethylene protector will remain on the nipple all the time, but only is taken away at the breastfeeding time. The examination was done through the photographic slides and oral descriptive scale in the 1st, 3rd, 5th and 7th days. The oral descriptive scale is a 6-degree tool in which 0 = no pain and 6 = severe pain. Edema, blister, skin color change, desquamation and ecchymosis are independently examined according to the provided slides and by two experts. The fissure mean in the experimental group was 1.17 while it was 1.34 in the control group. This difference was statistically significant (p<0.001), there was also a significant statistical difference in the pain severity mean between these two groups (p<0.05) [31].

When the painful and injured site is heated, the area blood flow rate is in fact increased. Increasing the nitric oxide production by the vascular endothelial cells is the reason of increased blood flow rate through the heat. Increased blood flow rate in the injured site through the oxygen and nutrients will help to relive the pain and increase the wound healing rate [32].

The research units in the study of Lavergne (1995) were randomly placed in one of these three groups for five days: the tea bag compress on one breast and the hot water compress on the other, the hot water compress on one breast and non-treatment on the other, the tea bag compress on one breast and non-treatment on the other. The compress was done as follows: the research units put the tea bag and the breast pad in hot water then remove its extra water and put it on the breast for 15 minutes, the process repeats 4 times a day. The opposite breast, which had not received any treatment, was recommended to be exposed to the air for 15 minutes. Each sample was also a control group. The nipple soreness rating scale was used to determine the pain severity in which 0=no pain and no fissure, 5= the nipple fissure and severe pain during breastfeeding. The fissure status was also scored between 0 (no fissure) to 3 (visible fissure). The mother completely used these tools daily and after breastfeeding. The results showed that there was a significant statistical difference in the pain relief between the two groups of the hot water and the tea bag compress than to non-treatment group. The hot water and the tea bag compress were more effective than non-treatment. In the hot water and tea bag compress comparison, we have found that both were equally effective in the pain relief and there was no significant statistical difference in-between [33].

C. officinalis is an annual and herbaceous herb containing effective ingredients like flavonol glycosides, essential fatty acids, saponins and flavonoids [34]. Its flavonoids prevent the release of histamine and the production of prostaglandins as well as improving the inflammation and pain. Saponins will reduce the white blood cell movement to the flamed site by decreasing the capillary permeability and reducing histamine and then prevent plasma release into the tissue and also have the antibacterial and antifungal properties [35, 36].

Kazemirad et al (2013) has divided the research units into 2 groups in his study. In the experimental group, calendite ointment (combination of hydro alcoholic extracts of the marigold and Echinacea angustifolia) was used 3 times a day after breastfeeding and the control group rubbed their breast milk around the nipple fissure. Both groups were taught the correct breastfeeding methods and subsequently were treated for a week. The nipple fissure score was measured before the study and in the 3rd and 7th days after the study and recorded using Store Scale by the researcher. This scale has five degrees, 0 (the minimum score), 4 (the maximum score). This scale will assess redness, edema and inflammation, the pain, the nipple fissure and bleeding. The results indicating that the fissure severity was homogeneous between both groups and its reduction in the 3rd day had no significant decrease (p = 0.2), but the experimental group showed a significant difference at the 7th day (p = 0.006). According to these results, the calendit-E ointment was more effective than the breast milk [37].

Jujube with the scientific name of Z. jujube Miller is a fruit belongs to the Ramanacea family. It contains potassium, phosphorus, calcium, zinc, tannins, phenol flavonoids, phenolic acids, protein and fatty acids. Saponins and polysaccharides in the jujube have a major role in the safety activities and anti-inflammatory. Flavonoids, cyclopeptides, alkaloids and terpenes have anti-aesthetic, anti-microbial and anti-inflammatory properties. Gallic acid, catechins, caffeic acid, coumarines and chlorogenic acid are effective in reduction of inflammation [38, 39].

Shahrahmani et al (2016) divided the women who had their first delivery and went to the women's clinic to do their baby’s thyroid test on the third day after the birth and complained of their nipple fissure and pain into 2 groups as follows: they were selected based on a target-based method and input criteria-based and then were randomly grouped in the lotion of jujube or breast milk. The breastfeeding women in the control group rub 5 drops of their breast milk on their areola 5 times a day after breastfeeding and the experimental group do the same with 0.5 ml of jujube lotion. A research assistant who was not aware of the treatment type measured and recorded the pain severity before the intervention 7th and 14th days after the treatment through a visual scale of the pain assessment. The pain severity score had no significant statistical difference before the intervention in both groups, but there was a significant statistical difference in both groups at 7th and 14th days after the treatment (p = 0.02 and p = 0.01). The results showed that the jujube lotion is more effective in the nipple pain relief than the breast milk [40].

It is from the Soglas and asparagus genus. Because of the combinations such as glucomannan polysaccharide, carboxy peptidases, glucose, and all kinds of vitamins in it, the properties like antioxidant, antibacterial, antifungal, anti-inflammatory and healing are appeared [41]. The A. vera anti- inflammatory effect is attributed to the flavonoids, vitamins A and C, salicylic acid (effective in inhibiting the formation of bradykinin and histamine) and arachidonic acid oxidation in it (effective in inhibiting prostaglandin synthesis) [42].

Tafazoli et al (2010) firstly selected the research units based on the target-based method and then divided them randomly into 2 groups: the experimental group (A. vera gel) and the control (Lanolin) group. Both groups were taught the correct breastfeeding methods and the correct use of the drug. The mothers were asked to rub the drug 3 times a day after breastfeeding for 7 days. The researchers were not aware of the treatment type. The researchers completed the Store Scale before the study and in the 3rd and 7th days during the study by visiting the women. The nipple fissure’s mean score was as follows: in the A. vera gel group before the study = 3.04, in 3rd day= 1.26 and in 7th day= 0.26. In the lanolin ointment group before the study= 3.1, in 3rd day= 1.7 and in 7th day= 1.02. Both groups were homogeneous in the nipple fissure mean score before the study (P> 0.05). However, in the 3rd (p=0.048) and 7th (p=0.003) days there was a significant difference between them. On the basis of the results the A. vera gel was more effective in the nipple fissure healing than the lanolin ointment alone [6].

Carvone, limonene, menthol and menthone are the ingredients in mint oil. Menthol has a specific receptor in the cell membrane and increases the threshold of cell stimulation through these receptors as well as blocks the flow and transition the pain signal by effecting on Kappa-opioid receptors and then leads to the pain relief and reduction [43, 44].

Four drops of menthol essence and breast milk were prescribed in Ali Akbari’s et al study (2014) for the intervention and the control group, respectively. The nipple fissure and the pain severity were assessed using Amir Scale and VAS tool, respectively before and in the 10th and 14th days after the treatment. The nipple fissure severity mean in the experimental group was 8.31 mm before, 6.51 mm in the 10th day and 2.24 mm in the 14th day after treatment, respectively. It was 8.02 mm before, 7.39 in the 10th and 5.76 mm in the 14th day after the treatment in the control group. In the experimental group the pain severity mean was 14 8.55, 4.26 and 1.32 mm in days 3, 10 and 14, respectively, while it was 8.41, 6.67 and 4.32 mm in the control group, respectively. The results indicated that menthol essence relieved the pain and healed the nipple fissure [45].

Shanazi et al (2015) has examined the effect of mint, lanolin and dexpanthenol on the nipple fissure. Mothers in this study were randomly grouped in 3. The lanolin tube contained pure lanolin without additives, the mint tube contained carbopol, methyl paraben, triethanolamine, glycerin and 2% mint and the dexpanthenol contained 5% B complex analogue. The tubes were similar in appearance. The researcher and the research units were not aware of the treatment type. People in 3 groups were treated 3 times per day for 2 weeks. The fissure status was examined before the intervention, in the 3rd, 7th and 14th days after the treatment. The results suggested that lanolin, dexpanthenol and mint had a similar effect on the nipple fissure treatment [22].

Sayyah Melli et al (2007) had randomly divided the research units into 3 groups after babies’ examination and mothers’ breast physical examination. The lanolin, mint gel and placebo were similar in appearance and were marked with A, B and C. The participants were taught the correct breastfeeding methods and the way of the drug usage. The assessment was done in the 4th, 7th, 10th, 14th and 42nd for the pain and fissure. The Amir Scale was used to determine the fissure status. The total fissure incidence was 11% in all three groups. (6.9% in the lanolin group, 3.8% in the mint group and 22.6% in the placebo group), which was statistically significant (p= 0.01). The results showed that mint gel was more effective in the nipple fissure prevention than each one of lanolin and placebo [46].

The crystalline hydrocarbon has derived from azulene that is taken from the gum of the Guaiacum tree. The Guaiac has these properties: anti-inflammatory, anti-infectious, anti-oxidant, anti-fungal, and epithelialization stimulant [47].

API et al (2005) measured the effect of the Guaiazulene ointment on prevention of the nipple fissure incidence. 153 mothers with no nipple fissure were randomly grouped into one of two groups: milked breast milk and Guaiazulene ointment (0.05 % w/w). The experimental group was asked to rub the ointment after each breastfeeding at least 4 times a day for 1 month and the control group were advised to rub their breast milk on the nipple after each time of breastfeeding and expose it to the air for 1–2 minutes to be dried. The VAS tool measured the pain severity in the 15th and 30th days after the intervention. Women’s fissure was examined on the 30th day after the treatment. The total fissure incidence was 31.4%, 18.4% of which was in the Guaiazulene group and 44.2% of which was in the breast milk group. In the 15th day the Guaiazulene group nipple pain (p<0.05) was significantly lower than the breast milk group nipple pain in the 30th day (p<0.05). The results indicated that using Guaiazulene ointment (0.05%w/w) will effectively prevent the nipple fissure incidence [48].

The WHO has introduced P. oleracea as the most commonly used herbal medicine and it is attributed as the global Panacea. Its anti-inflammatory and anti-nociceptive effects are attributed to its available flavonoids, tannin, saponins and terpenoids [49–51]. The Omega 3 in P. oleracea is the most probable agent responsible for the anti-inflammatory effect by reducing inflammatory cytokines [52].

Niazi et al (2017) has randomly divided 86 breastfeeding women suffered from the nipple pain into two groups of 43 people after the explanation of the study goals and methods and obtaining a written consent letter: P. oleracea ointment and lanolin. Both groups were taught the correct breastfeeding method and drug usage. The researcher had measured and recorded the nipple pain score before the intervention and in the 3rd and 8th days after the treatment using the pain numerical rating scale. The results showed a significant difference in the pain severity in the 3rd and 8th days than before in both groups and the pain severity was decreased in both (P<0.001). The pain severity was lower in the 3rd and 8th days in the P. oleracea group than to the lanolin group (P<0.001) [53].