This study is aimed at constructing and evaluating a prediction model of severe abdominal pain post-transcatheter arterial chemoembolization in patients with HBV-related primary liver cancer. n = 120) and validation group (n = 40) in a ratio of 3 : 1. Visual analog scale (VAS) was used to assess pain severity. 120 patients in the modeling group were divided into no/mild abdominal pain group and severe abdominal pain group. The clinical data of the patients, including gender, age, TACE treatment history, vascular invasion, maximum diameter of tumor, infarction degree, preoperative Eastern Oncology Collaboration Group (ECOG) score, and Lipiodol dosage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model for severe abdominal pain post-TACE.  Patients with HBV-associated primary liver cancer who received transarterial chemoembolization (TACE) from March 2019 to March 2022 in the Interventional Therapy Department of our hospital were selected as the subjects, and the included 160 patients were randomly divided into modeling group (P < 0.05), but not related to gender, age, vascular invasion, and Lipiodol dosage . Logistic regression analysis showed that TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score were all independent influencing factors for acute abdominal pain post-TACE in HBV-HCC patients . The prediction model equation was Y = −3.673 + 1.722 × TACE treatment history + 1.175 × tumor maximum diameter + 2.064 × infarction degree + 1.555 × preoperative ECOG score. Goodness-of-fit test results showed no significant difference between the established prediction model and the observed value  and R2 = 0.821, suggesting that the prediction ability of the model was relatively accurate. ROC analysis results showed that the area under the curve (AUC) of severe abdominal pain after TACE was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963) in the modeling group and the verification group, respectively.  A total of 116 patients (72.50%) had severe abdominal pain after TACE. Univariate analysis showed that severe abdominal pain after TACE in the modeling group was associated with TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score (all  TACE treatment history, tumor maximum diameter, infarction degree, and preoperative ECOG score are independent influencing factors for severe abdominal pain post-TACE in patients with HBV-HCC, and the prediction model established on this basis has good application value. Primary liver cancer is one of the most common malignant tumors in China, with 410,000 new cases and 390,000 deaths in 2020, ranking the fourth in the incidence of malignant tumors and adversely affecting the health of Chinese residents, with a 5-year survival rate of only 14.1% . With thn = 120) and the validation group (n = 40) according to the ratio of 3 : 1. All the subjects in this study signed informed consent for the study, and this study was approved by the medical ethics committee of the hospital.Patients with HBV-related primary liver cancer who received TACE from March 2019 to March 2022 in the Interventional Therapy Department of our hospital were selected as the study subjects. Inclusion criteria are as follows: (1) primary liver cancer was confirmed by pathology and met the diagnostic criteria ; (2) >20Referring to “Expert Consensus on Pain Management after Adult Surgery” , the traAccording to the requirement that the variables in the risk factor survey should be 5 ~ 10 times the sample size, this study included 8 variables through previous research reports and clinical practice, including gender, age, TACE treatment history, vascular invasion, tumor maximum diameter, infarction degree, preoperative ECOG score , and Lipt-test. The counting data were represented by the number of cases or rates. The comparison of counting data between two groups was performed by the χ2 test. The variables with statistical significance in the univariate analysis were assigned and included in the multivariate analysis. Multivariate analysis was conducted by logistic regression model, and ROC curve was used to evaluate the predictive value of the model for predicting severe abdominal pain post-TACE. ROC curve plotting was performed using the GraphPad 6.0 software. The goodness-of-fit test method was used to test the difference between the model established in this study and the actual observation. P > 0.05 indicated that the model has good feasibility. P < 0.05 was considered statistically significant.SPSS21.0 was used to analyze the collected experimental data. The measurement data in accordance with the normal distribution were represented by A total of 116 of 160 patients developed severe abdominal pain after TACE, with an incidence of 72.50%. The duration of pain in patients with severe abdominal pain was 55-220 min, with an average of 125 ± 36 min. The number of patients who scored 4-6 points in VAS at 1 h and 6 h after TACE was relatively high, and the number of patients who scored 1-3 points in VAS at 12 h and 24 h after TACE was relatively high .P > 0.05, There were no significant differences between the modeling group and the validation group in gender, age, TACE treatment history, vascular invasion, tumor maximum diameter, infarction degree, preoperative ECOG score, and Lipiodol dosage , but not related to gender, age, vascular invasion, and Lipiodol dosage , maximum tumor diameter , infarction degree , and preoperative ECOG score . The final logistic regression analysis results showed that TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score were all independent factors influencing severe abdominal pain post-TACE in HBV-HCC patients , where P is the probability of severe abdominal pain after TACE, e is the natural logarithm, and Y = −3.673 + 1.722 × TACE treatment history + 1.175 × maximum tumor diameter + 2.064 × infarction degree + 1.555 × preoperative ECOG score. Goodness-of-fit test results showed that there was no significant difference between the prediction model of severe abdominal pain post-TACE and the observed value , and R2 = 0.821, suggesting that the prediction ability of the model was relatively accurate. ROC analysis results showed that the AUC of severe abdominal pain post-TACE in the modeling group and the verification group was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963), respectively , there were 841,000 cases and 781,000 deaths about liver cancer worldwide in 2018 . The incPrevious studies , 25 haveIn this study, prediction model was established. The AUC of severe abdominal pain after TACE in the modeling group and the validation group was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963), respectively, indicating that the prediction model established in this study had a high predictive value for severe abdominal pain post-TACE. At present, severe abdominal pain post-TACE has a high incidence and has certain subjectivity with the existence of misdiagnosis and missed diagnosis. The present model can directly predict the risk factors of severe abdominal pain post-TACE without the influence of blood environment and exogenous factors. The application of this model combined with clinical indicators can improve the sensitivity of diagnosis and help patients to detect severe abdominal pain post-TACE at an early stage, so that treatment and control measures can be adopted as soon as possible to avoid further development and aggravation of the disease.In conclusion, severe abdominal pain post-TACE is associated with multiple factors including TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score. In this study, the logistic regression risk prediction model of postoperative severe abdominal pain post-TACE established based on the above factors has a good prediction effect, and clinical intervention can be carried out according to the above risk factors to reduce the incidence of postoperative severe abdominal pain. However, this study also has shortcomings such as small sample size and only the visual analog scale (VAS) used to assess the severity of pain. In the future, the research sample can be further expanded, and multiple means of assessing pain severity can improve the reliability of the study to provide more support for clinical application.


Knee osteoarthritis is a common global problem, especially in overweight and obese people. It is not clear that weight loss is a factor for pain reduction in these patients or dietary components are important. Herein, we compared the effects of Mediterranean (MD) and low-fat diet on pain, stiffness, and physical function in patients with knee osteoarthritis. /n = 43), low-fat diet (n = 43), and control group (regular diet) (n = 43) for 12 weeks by the blocked randomization method. Total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and its subscales and anthropometric indices were compared among the groups at the baseline and end of the study.  In this randomized feeding trial, 129 patients with knee osteoarthritis were enrolled. Participants were randomly allocated to the MD , but there was no significant difference between the MD and low-fat diet groups (p = 0.2). Pain was significantly decreased in the Mediterranean-style compared with the low-fat (p = 0.04) and regular (p = 0.002) diet groups. Physical function was significantly improved in the MD compared with the regular diet group (p = 0.01), but had no significant difference with the low-fat one. Stiffness had no significant difference among the dietary groups.  Weight and waist circumference reduction was significantly higher in the MD and low-fat diet groups compared with the regular group (IRCT20200929048876N1. Pain severity was reduced in the MD group, but no significant change was reported in patients on low-fat and regular diets. It seems that dietary components in the MD, regardless of weight loss effect, are effective on pain reduction in patients with KOA. The present study was registered in the IRCT under the code of  Osteoarthritis (OA) is the most predominant form of arthritis, affecting about 230 million people in the world . Knee OAIn fact, the risk of OA is higher in overweight and obese people, and the prevalence is increasing because of aging in the communities . ObesityAccording to the research, there is no study comparing the effects of MD and low-fat diet in a weight loss program in patients with KOA.IRCT20200929048876N1.The present study is a randomized single-blinded feeding trial that was ethically approved by the ethics committee of Zanjan University of Medical Sciences, Zanjan, Iran (IR ZUMS REC 1398.426) on 18 Jan 2020. The aim of study was prescribed to each participant. The signed informed consent form was gathered before the study enrollment. All procedures were performed according to the CONSORT clinical trial guidelines for human studies. Registration number of clinical trial: the present study was registered in the IRCT under the code of 2 were included in the present study from February to September 2020. The disorder of participants was diagnosed less than one year ago according to the American College of Rheumatology criteria (20). Patients with the history of joint replacement, chronic diseases including inflammatory rheumatoid arthritis, cardiac, hepatic, kidney failure, cancer, acute myocardial infarct, type 1 and 2 diabetes mellitus, stroke, mental and nervous diseases, and serious injuries from injection or oral administration of corticosteroids for the past 6 month, intake of alcohol, and cigarette were excluded. Patients who are on a certain diet, with recent weight loss more than 4 kg during the last 2 month, allergic and sensitive to fish supplements, undergoing physiotherapy or had physiotherapy to reduce pain over the past month, and opioid consumption or nonsteroid anti-inflammatory drugs on a daily and continuous basis were not included in the present study. Unwillingness to follow a prescribed diet was another exclusion criterion.One hundred and twenty-nine patients with KOA between ages 40–75 yrs and 25 BMI<35 kg/mBlocked randomization was used as three groups with 15-number blocks including five participants in each group. Randomization unit was person, and the random allocation software was used for this purpose. Random coded boxes were used for concealment. At this method, cans with similar weight, shape, and color, which were numbered according to the random sequences, were used. Three-day food diary (two regular days and one holiday) was gathered from each patient at the baseline. Then, patients were randomized to the three dietary groups based on 28 kcal/kg/day: (1) MD contains 35%, 50%, and 15% of calorie from fats, carbohydrates, and protein, respectively. Patients receive 27–37 gr fiber in this dietary pattern. Patients were emphasized to receive at least half of their grains from the whole grains. Patients can consume 150 gr of red meat each month. Olive oil can be used for salad and canola oil for frying. At least one serving of legumes and nuts must be included in the daily diet. Low-fat dairies can be consumed, and six glasses of water must be drunk each day. Mercury-free fish oil supplements were delivered to each patient to receive two times per week; (2) low-fat diet contains 20%, 65%, and 15% of total daily calorie from fats, carbohydrates, and protein, respectively. In this dietary pattern, patients did not receive any advice and dietary servings were determined for each patient. Patients in the control group were asked not to change their dietary pattern. Dietary interventions were pursued for 12 weeks. All the participants were asked not to change their activity and had mild walking on a flat surface for 30 min. Physical activity was assessed by the international physical activity questionnaire (IPAQ) short form. To control the patient's adherence, the nutritionist called each person at the end of each week and reminded the tips of diets. In addition, three-day food diary questionnaires were gathered at the end of each month from the patients for compliance and adherence check. Patients with compliance lower than 80% were excluded from the study.The Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire was filled by an internal medicine resident to assess the patient's opinions on their pain and related problems considering their KOA. This questionnaire consists of five items for pain, two items for stiffness, and seventeenth items for physical function . Visual t-test. To adjust the effect of baseline weight of patients on the outcomes, the linear regression model was performed. Significance was considered at p < 0.05 in all comparisons.Statistical analyses were performed using IBM SPSS Statistics, version 25 . All data were first tested for normality by the Kolmogorov–Smirnov test. To assess difference in sex among the groups, as a qualitative variable, the Chi-square test was used. Other quantitative variables including weight, age, WC, WOMAC components, and VAS were analyzed by the ANOVA test, followed by the post hoc analysis. Before and after differences in the assessed variables were analyzed by the paired-sample The study protocol is illustrated in p = 0.36), sex (p = 0.4), pain (p = 0.22), stiffness (p = 0.84), physical function (p = 0.49), and visual scale analogue (p = 0.4) before the intervention, but weight had a significant difference among the groups at the baseline, and this difference was between the low-fat and regular diet groups (p = 0.04). Weight and WC were significantly decreased in the low-fat and MD groups after 12 weeks (p < 0.001). A significant difference was shown among the dietary groups in pain (p = 0.03). Pain was significantly decreased in the MD compared with the low-fat diet at the end of the study (p = 0.02). Pain, stiffness, physical function, and VAS were significantly reduced in all groups after intervention compared to the baseline , but there was no significant difference between the MD and low-fat diet groups (p = 0.4). Pain was significantly decreased in the MD diet group compared with the low-fat (p = 0.04) and regular (P = 0.002) diet groups. Physical function was significantly improved in the MD compared with the regular diet group (p = 0.01), but had no significant difference with the low-fat one. Stiffness had no significant difference among the dietary groups. Pain severity (VAS) was significantly reduced in the MD compared with the regular diet group (p = 0.004) (Weight and WC reduction was significantly higher in the MD and low-fat diet groups compared with the regular group (= 0.004) .p = 0.006). The knee pain in walking decreased 75% in the low-fat diet after 12 weeks of intervention, but increased 62% in the regular diet group. The knee pain in standing situation improved 100% in the MD group . Right and left knee pain had no significant difference among the groups, but the left knee pain was significantly decreased after dietary interventions compared with the baseline . Morning stiffness decreased 81% in the MD group after 12 weeks of intervention .The interaction effect between the time and diet was assessed on the WOMAC components. There was a significant effect between the low-fat diet and time on knee pain in walking (95%CI 1.1–2.29, Herein, we showed that weight and WC significantly decreased in the MD and low-fat diet groups compared with the regular diet. The pain and physical function alteration were significantly higher in the MD group compared with the regular one, but there was no significant difference between the low-fat and regular diet in these parameters. Moreover, pain reduction was significantly higher in the MD group than in the low-fat diet group. Total stiffness had no significant difference among the groups, but morning stiffness decreased 81% in the MD group at the end. Knee pain in the standing situations improved 100% in the MD group compared with others. Knee pain in walking decreased 75% in the low-fat diet group. No patient received pain-relief drugs during the study.γ and regulates innate and adaptive immune mechanisms to decrease inflammation [vs. high doses of fish oil on the WOMAC pain score of patients with KOA at 3, 6, 12, and 24 months. Results showed that the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group [KOA, as a widespread complication with many physical, cognitive, and emotional side effects, is increasing due to the aging of the communities. Polypharmacy is a main problem in the aged people because of drug interactions or abuse. Therefore, there is a need to find alternate pain management approaches . In a reammation . Oleocanammation , 30. Preammation . In thisse group . Decreasse group , 33.Studies on the effect of MD in patients with KOA compared this dietary pattern with the usual diet. There is no study to compare the effects of MD pattern with the low-fat diet in a weight loss program. In the present study, we showed that although there was no significant difference in the amounts of weight loss between the MD and the low-fat diet, the pain severity decreased significantly in patients on the MD compared with the low-fat diet. The major limitation of the present study was the method of the dietary adherence assessment. However, the nutritionist called to each person at the end of each week for reminding the dietary tips and gathered the three-day food records; exact adherence not be measured. Moreover, outcomes were analyzed by the questionnaires that are dependent to the patient's opinion. Future studies in other dietary cultures, by considering accurate outcomes such as a radiographic test or biochemical markers, are needed to trust the results.Calorie restriction, in any dietary pattern, leads to weight loss. However, weight loss had no significant difference between the low-fat and Mediterranean dietary pattern, and pain severity was reduced in the MD group. It seems that dietary components in the MD are effective on pain reduction in patients with KOA.


Pain is a highly debilitating emotional and sensory experience that significantly affects quality of life (QoL). Numerous chronic conditions, including cancer, are associated with chronic pain. In the setting of malignancy, pain can be a consequence of the tumor itself or of life-saving interventions, including surgery, chemotherapy, and radiotherapy. Despite significant pharmacological advances and awareness campaigns, pain remains undertreated in one-third of patients. To date, opioids have been the mainstay of cancer pain management. The problematic side effects and unsatisfactory pain relief of opioids have revived patients’ and physicians’ interest in finding new solutions, including cannabis and cannabinoids. The medical use of cannabis has been prohibited for decades, and it remains in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context for its usage has become more permissive. Various preclinical and observational studies have aimed to prove that cannabinoids could be effective in cancer pain management. However, their clinical utility must be further supported by high-quality clinical trials. Pain is an unpleasant emotional and sensory experience that is associated with potential or actual tissue damage. More than 70% of cancer patients experience pain, which impacts their emotional and physical dimensions . The treIn recent years, alternative pharmacological interventions for cancer pain, including cannabis-based medicines, have been widely explored. There are a series of medications available, including plant-derived cannabinoids, synthetic cannabinoids, magistral preparations of cannabis plant derivatives, nutritional supplements and experimental medications. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most studied compounds in the cannabis family . These cThis review aims to provide an update on the use of cannabis-based medicines for cancer pain management. In addition, the current study aims to inform the medical oncology community about the use of cannabis as a possible therapeutic option for pain relief.Pain affects 50–90% of cancer patients and is one of the most disabling symptoms . Cancer Strong opioids, including morphine, are the mainstay of moderate-to-severe cancer pain management.It is generally agreed that cancer pain management needs a comprehensive approach, including non-pharmacological and pharmacological modalities . The mosDespite the significant progress made in cancer pain management and awareness, pain is undertreated in one-third of patients, affecting the quality of life (QoL) . More thA large study including 4707 cancer survivors showed that two-thirds of the patients reported at least one obstacle to cancer pain management. The most vulnerable groups included less-educated, non-white, and patients with more comorbidities . AnotherOn the other hand, the aberrant use of opioids among patients is a serious concern in the U.S., and therefore, has led to discussions regarding epidemiological modeling and economic analysis to better allocate limited resources to attenuate the effects of the ongoing opioid epidemic. . In a reCurrently, an increasing number of patients with chronic cancer pain are seeking alternative treatment options. Therefore, interest in cannabis and cannabinoids has grown considerably in recent years. In addition, such products are increasingly available in many countries as the general attitude towards medical cannabis and cannabinoids has shifted .Cannabis sativa L. has a long history of medicinal use. CBD and THC are the two components with the highest concentrations in Cannabis sp. , GPCR18, serotonin, and opioid receptors ,41,42,43The administration of cannabinoids has been shown to suppress all neurophysiological and behavioral responses to nociceptive stimuli. These compounds were found to exert their anti-nociceptive effect by an action on the peripheral nerves, direct activity in the brain, or direct spinal activity . TherefoTHC is the primary psychoactive ingredient of cannabis and can promote dependency among chronic users as it interacts with the dopaminergic system . THC hasCBD is the second most abundant component of cannabis and has broader medical applications than THC. However, CBD does not have THC-like or toxic drug effects but has been reported to reduce inflammation, muscle spasms, seizures, and anxiety . There aCannabinoids are highly lipophilic substances that are stored in spleen and adipose tissues. After inhalation, peak plasma levels of CBD and THC are rapidly achieved within 3–10 min . The bio®) is an almost 1:1 ratio of plant-based THC and CBD and is licensed for treating spasticity in multiple sclerosis [The use of cannabis for recreational or medical purposes has been banned for decades. Several cannabinoid drugs have been developed to date. Nabiximols  in a group of 10 patients with cancer treated with opioids (mainly methadone) [The first placebo-controlled trial published in 1975 reported that 15 and 20 mg THC oil provided more pain relief than placebo (thadone) . A subsethadone) .®)  administered orally in 177 opioid-refractory, advanced pain cancer patients. The results showed a statistically significant improvement in the mean pain score in favor of nabiximols compared with placebo (p < 0.024). Moreover, patients treated with nabiximols required fewer doses of breakthrough pain medication [In addition to oils, oromucosal sprays have been widely used in clinical trials to administer cannabis-based medicines. Johnson et al. investigated, for the first time, the analgesic efficacy of mixed cannabis extracts and nabiximols (Sativexdication .p = 0.037). The U.S. subgroup of patients had a lower opioid baseline dose and increased exposure to cannabis in the past. These findings led to the hypothesis of reduced downregulation of opioid receptors, resulting in enhanced synergy between cannabinoids and opioid receptors and, therefore, a better outcome [The analgesic efficacy of nabiximols was further investigated in a double-blind, randomized, placebo-controlled trial on cancer patients suffering from severe pain  scores ≥ 4 and ≤8) poorly controlled by opioids. The design implied a two-week, self-titration and tolerability phase, followed by a three-week treatment period. However, the primary efficacy endpoint was not achieved. The negative outcome of this study could be explained by several contributing factors, including the high mortality rate reported in the study population and increased dropout rate. Furthermore, self-reported NRS scores could be significantly influenced by variations in day-to-day mood, especially in frail cancer patients. Moreover, a post hoc analysis showed that Sativex was effective only in U.S. cancer patients ( outcome .p < 0.001). More importantly, 9.9% of the patients reported a decrease in opioid dose, 36% discontinued opioid use, and only 1.1% increased opioid dosage. Overall, 30% of the patients reported at least one side effect: dry mouth, dizziness, sleepiness, increased appetite, and psychoactive effects [A long-term observational study conducted in Israel evaluated the safety and efficacy of medical cannabis in 3619 cancer patients. All participants received a mixture of 16 THC and CBD strains administered with various concentrations of oils and/or inflorescences . After one month, 19.5% of the active users (2082) reported a moderate improvement, and 66.3% reported a significant improvement in their general condition. In addition, 8.3% of the patients experienced side effects, including tiredness, cough, nausea, dizziness, confusion, and disorientation. After six months, among the active users (1211), 45.1% reported moderate, and 50.8% reported significant improvements. Moreover, the percentage of patients reporting good quality of life was 68.5% compared to 18.7% at baseline  of five .In addition to the limited evidence for their efficacy, cannabinoids carry the risk of adverse events, similar to any other existing therapeutic agent. Over the past 40 years, almost 5000 adverse events associated with the medical use of cannabinoids have been reported . The mosThe use of cannabis has been extensively debated, based on the presumption that it can lead to dependence and addiction. Statistics show that approximately 9% (1 out of 11) of all people who have ever used cannabis will experience dependency at some point in their lives, and the percentage is almost double if the use begins during adolescence . It is eThe medical use of cannabis has been prohibited for many years, and it is still listed in Schedule 1 of the Misuse of Drugs Regulations. Currently, the legal context of its use is becoming more permissive. Based on the expanding evidence regarding its medical applications, the WHO proposed that cannabis should be rescheduled within international laws. Therefore, in many European countries , ThailanCancer pain is a highly debilitating syndrome that has a significant impact on QoL and is sometimes challenging to treat using the available therapeutic options. As life expectancy in cancer patients increases owing to remarkable improvements in therapies, cancer pain associated with life-saving interventions  will become more prevalent. Although the results from preclinical trials are encouraging, there is a paucity of translatable evidence in clinical studies to support the use of cannabinoids for cancer pain management. Further clinical trials, more extensive and more rigorous, are needed to establish their clinical efficacy, dosing, and, not least, their potential interactions with other drugs. It is essential to carefully analyze the decision to use cannabinoids for cancer pain to avoid misuse, addiction, or dependency.


At the beginning and end of the protocol, patients' pain levels were assessed using the numerical rating scale  for pain (NRS Pain). During the protocol, electrocardiogram and respiratory effort signals were measured, from which heart rate variability (HRV) and respiration pattern variability (RPV) were extracted. Pre- to post- changes (denoted with a Δ) were computed for all measures. Δ NRS Pain scores were lower (P = 0.045) for the active group (mean ± standard deviation: −0.8 ± 2.4) compared to the sham group (0.9 ± 1.0). A positive correlation existed between Δ NRS pain scores and Δ RPV . Following adjustment for device group, a negative correlation existed between Δ HRV and Δ NRS Pain . This randomized, double-blind, sham-controlled pilot study provides the first evidence of tcVNS-induced reductions in pain in patients with OUD experiencing opioid withdrawal. This study also provides the first quantitative evidence of an association between breathing irregularity and pain. The correlations between changes in pain and changes in objective physiological markers add validity to the data. Given the clinical importance of reducing pain non-pharmacologically, the findings support the need for further investigation of tcVNS and wearable cardiorespiratory sensing for pain monitoring and management in patients with OUD.Over 100,000 individuals in the United States lost their lives secondary to drug overdose in 2021, with opioid use disorder (OUD) being a leading cause. Pain is an important component of opioid withdrawal, which can complicate recovery from OUD. This study's objectives were to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS), a technique shown to reduce sympathetic arousal in other populations, on pain during acute opioid withdrawal and to study pain's relationships with objective cardiorespiratory markers. Twenty patients with OUD underwent opioid withdrawal while participating in a two-hour protocol. The protocol involved opioid cues to induce opioid craving and neutral conditions for control purposes. Adhering to a double-blind design, patients were randomly assigned to receive active tcVNS ( The opioid epidemic has been deemed a public health emergency . In the A recent study of vagus nerve stimulation (VNS) delivered percutaneously to the auricular branch of the vagus nerve observed significant reductions in opioid withdrawal symptoms within hours . The stuConsidering the promising results of previous literature and the underlying physiology, we hypothesized that tcVNS would reduce behavioral and physiological manifestations of opioid withdrawal in patients with OUD. Our group's recent randomized, double-blind, sham-controlled pilot study evaluated this hypothesis and found statistically significant reductions in opioid withdrawal symptoms, subjective distress, and heart rate in patients receiving active tcVNS, compared to patients receiving sham stimulation . We alsoAs part of a protocol approved by the institutional review boards of Emory University (IRB00117320) and the Georgia Institute of Technology (H20203), the psychological and physiological effects of tcVNS were studied in patients undergoing acute opioid withdrawal. Patients intending to start medication for OUD were recruited in partnership with Emory Healthcare Addiction Services and Alliance Recovery Center . To participate in the study, patients were required to be between the ages of 18 and 80 years old and meet OUD criteria according to the Structured Clinical Interview for DSM-5 (SCID). Patients who had prior experience with tcVNS, a history of carotid atherosclerosis, cervical vagotomy, schizophrenia, schizoaffective disorder, bulimia, meningitis, traumatic brain injury, neurological disorder, a loss of consciousness for greater than one minute, or any other serious medical or neurological illness were excluded. Patients were also excluded if they were implanted with a device , pregnant, or breastfeeding at the time. All participants provided written informed consent after receiving a complete description of the study. Data collection took place either at Alliance Recovery Center or at the Emory University School of Medicine.Study participants abstained from substance use for a minimum of eight hours prior to the in-lab protocol, as illustrated in In this double-blind study, patients were randomly assigned to receive either active tcVNS or sham stimulation using simple randomization. The active and sham devices operated and appeared identically, differing only in the stimulation delivered. An individual not involved in recruitment, data collection, or analysis assigned pre-numbered stimulation devices to participant identification numbers. The entire dataset was then collected prior to unblinding. Patients and researchers were blinded to device group throughout screening, clinical interviews, and data collection.For exactly two minutes at a time in accordance with the protocol shown in Perceived pain was measured at the beginning and end of the protocol using the Numerical Rating Scale (NRS) for pain, as shown in Electrocardiogram (ECG) and respiratory effort (RSP) signals were measured throughout the protocol at the locations shown in ECG signals were processed using the pre-processing, quality assessment, and feature extraction methods of prior work ; all of In this study, two well-established time domain metrics were used to quantify HRV: the standard deviation of NN intervals (SDNN) and the root mean square of successive differences (RMSSD) . The SDNi), expiration time (Te), and respiration rate (RR) time series were then used to estimate RPV.RSP and ECG-derived respiration signals were processed using the pre-processing, quality assessment, and feature-level fusion methods of prior work ; all defi, Te, and RR time series. The CV is a standardized measure of dispersion computed by dividing the standard deviation by its mean and is one of the most widely used RPV metrics to date , CV(Te), and CV(RR) time series to be aggregated as desired for analysis. Please refer to via a moving window.Three RPV measures were computed in this study by quantifying the coefficient of variation (CV) for the T to date . As in p to date , the CV U test, after testing the data for normality using the Shapiro-Wilk test.To investigate the effects of tcVNS on opioid withdrawal-induced pain progression, the changes in the active and sham group's NRS pain scores were compared over the course of the protocol. Specifically, the initial measurement (pre-) of NRS pain was subtracted from the final measurement (post-) of NRS pain to obtain a Δ NRS pain score for each patient. These Δ NRS pain scores were compared between active and sham groups using the Mann-Whitney i), Δ CV(Te), and Δ CV(RR) were each computed similarly to Δ NRS pain by subtracting a baseline value from a final value. Specifically for each metric, the average during the second neutral video was treated as the baseline value, as done for heart rate in prior work  in the correlations between Δ physiological variability and Δ NRS pain ]. The CONSORT flow diagram for this study is shown in U = 23; P = 0.045) than the sham group's Δ NRS pain scores (0.9 ± 1.0). The active group's Δ NRS pain scores (−0.8 ± 2.4) were significantly lower , with a Spearman's correlation of 0.46 (P = 0.04). No other correlations were statistically significant unadjusted. Specifically, the Spearman's correlation between Δ NRS pain and Δ CV(Te) was 0.19 (P = 0.41), Δ CV(RR) was 0.37 (P = 0.11), Δ RMSSD was −0.22 (P = 0.35), and Δ SDNN was −0.40 (P = 0.08).A significant positive correlation existed between Δ NRS pain scores and Δ CV(Ti) remained statistically significant, as detailed in i), Δ SDNN, and both Δ CV(Ti) and Δ SDNN simultaneously. Results did not materially change after adjusting for Δ CV(Ti), Δ SDNN, and Δ CV(Ti) and Δ SDNN. Likewise, results did not materially change when adjusting for participant characteristics or baseline CV(Ti) and/or baseline SDNN, as detailed in the via tcVNS. The results of this study support the need to further investigate the use of tcVNS and ambulatory cardiorespiratory sensing for pain monitoring and management in patients with OUD.In this double-blind, randomized, sham-controlled pilot study, tcVNS reduced pain in patients with OUD experiencing acute opioid withdrawal. Specifically, a statistically significant decrease was observed in the difference between post-protocol and pre-protocol pain scores for patients in the active tcVNS group compared to the sham stimulation group. This study also found a statistically significant positive correlation between RPV and pain scores—the first quantitative evidence of an association between breathing irregularity and pain. HRV was also negatively correlated with pain in this data, corroborating previous literature. These correlations between changes in pain and changes in objective physiological markers add further validity to the pain measurements and their reductions In this study, tcVNS was found to counteract the potential increase in pain associated with acute opioid withdrawal. Patients in the sham group experienced increased pain or no change at all when comparing post-protocol pain measurements with those taken immediately preceding the protocol. In contrast, the majority of patients in the active group experienced decreased pain or no change at all (7 of the 9 in the active group). Although the outlier in the active group affected the mean difference observed between pre- and post- data, the statistical test ultimately used to compare the groups was rank based. Therefore, the active vs. sham difference's statistical significance was not driven by the single outlier. This tcVNS-induced reduction also cannot be attributed to the placebo effect, as the study was performed in a randomized, double-blind, sham-controlled manner. The potential for tcVNS to counteract pain during acute opioid withdrawal thus seems promising. Further investigation will be necessary to evaluate this potential in a larger sample.This finding of a tcVNS-induced reduction in pain during acute opioid withdrawal agrees with the broader literature on tcVNS for pain management. Studies of tcVNS for pain management have generally focused on headaches and migraines . NumerouThis analysis's positive correlation between changes in RPV and changes in perceived pain serves as the first quantitative demonstration of an association between pain and breathing irregularity. Previous studies exploring the relationship between pain and respiration have explored correspondences with parameters including respiration rate, respiration timings, inspiratory flow, and tidal volume –32. No aThe stronger correspondence between an inspiratory RPV measure and pain scores aligns with findings reported in previous literature. Previous studies on respiration and pain have demonstrated consistently that inspiratory parameters are particularly affected by pain. Pain typically increases inspiratory flow, either by decreasing inspiration time, increasing inspiratory volume, or a combination of both . Inspiravia respiratory sinus arrhythmia  are also compelling. This study's discovery of a positive correlation between pain and RPV needs further validation. Additionally, the stronger correspondence between pain and inspiratory RPV measures should also be investigated. This study did not statistically test the legitimacy of the researcher and patient blinding. Future blinded experiments should administer blinding surveys to patients and researchers, as applicable, before and after the protocol. This study's results may not fully generalize to left tcVNS, as the question of right vs. left tcVNS effects remains unanswered (The study's small sample size increased the analyses' margins of error and limited the statistical power, and no power analyses were performed answered . Future answered ] that chNew paradigms are necessary to manage opioid withdrawal-induced pain in patients with OUD. In this double-blind, randomized, sham-controlled pilot study, tcVNS was found to counteract increases in pain perceived by patients with OUD undergoing acute opioid withdrawal. A positive correlation was also found between changes in patients' RPV and changes in their pain scores; and a negative correlation was found between changes in patients' HRV and changes in their pain scores. As a non-invasive, non-pharmacological therapy, tcVNS poses minimal risk and is amenable to self-administration. RPV and HRV can also be measured using wearable physiological sensors. This study's findings are thus promising in the context of outpatient pain management during opioid withdrawal, as they indicate the potential for ambulatory pain monitoring and management. Further investigation is necessary to evaluate the use of tcVNS and wearable cardiorespiratory sensing for remote patient monitoring and management of pain in patients with OUD.


A decrease in pain sensitivity has been observed in patients with schizophrenia since the beginning of the twentieth century. This hypothesis further emerged during the last decades due to many clinical findings.To study pain responsiveness in patients with schizophrenia and explore its physiopathological mechanism through a review of the literature.We searched the Medline database with no time restrictions, and we hand searched the references of all retrieved reviews. After removing duplicates, we selected Full-text articles in both French and English languages. Keywords: “schizophrenia”, “pain”, “pain threshold”, “nociceptors”, “opioid receptors”, “opioid peptides”We have collected 399 references, we finally included 50 Articles only. Many case reports with heterogeneous types of pain concluded that despite the high prevalence of somatic comorbidities in patients with schizophrenia, there was no significant difference in pain complaints between patients with schizophrenia and controls. There was a positive correlation between the decrease in pain sensitivity and schizophrenia. Experimental studies supported a decrease in pain perception and a high pain threshold in those patients. The neurobiological hypothesis suggested the lack of pain transmission by the dysfunctional glutamatergic system and the involvement of the opioid system. these findings have been reported in patients even before starting treatment. The psychopathology theory pointed to the impact of psychotic defenses such as denial and cleavage in the phenomenon of pain insensitivity.The meticulous research of pain symptoms should be systematic in patients with schizophrenia and the hypoalgesia should be considered when dealing with somatic conditions in this specific population.


The present study explored the construction and application of a standardized postoperative pain-management procedure for patients with perianal abscess.Two study groups (the observation group and the intervention group) were established retrospectively. The observation group comprised 46 patients with perianal abscess who enrolled in this study between June 2019 and June 2020. The intervention group comprised 48 patients who enrolled in the study between July 2020 and July 2021. All patients were enrolled using the convenience sampling method. A pain-management team was established, and standardized procedure management was implemented in the intervention group, while routine pain management was implemented in the observation group. Indices related to the patients' postoperative pain-control satisfaction and rehabilitation were compared between the two groups.P < 0.05 for all).The patients' pain-control satisfaction, wound edema score, edema disappearance time, urinary retention, and defecation difficulty following intervention were better in the intervention group than in the observation group, and the differences were statistically significant (The implementation of the standardized postoperative pain-management procedure in patients with perianal abscess can effectively improve the patient's level of pain and satisfaction and promote rehabilitation. The incidence of postoperative pain in patients with perianal abscess is almost 100%, with most pain being at a moderate to severe level . PostopeIn 2018, the Chinese Medical Association's pain branch proposed that “standardized management is the sole way for pain management” . The staAs an effective intervention procedure, SOP has been used for the prevention and control of infectious respiratory disease , microsuThis case–control retrospective study was conducted in a tertiary hospital in Guilin, Guangxi, China. Two study groups (the observation group and the intervention group) were established. Patients in the observation group received routine pain management, and patients in the intervention group were treated under the standardized pain-management procedure on the basis of routine pain management. All patients were enrolled using the convenience sampling method.The inclusion criteria were (1) patients who met the diagnostic criteria of perianal abscess and had surgical indications , (2) patThe exclusion criteria were (1) patients with anemia, heart failure, and severe arrhythmia, or patients who suffered a cerebrovascular accident, (2) patients with serious liver and kidney insufficiency, (3) patients with mental illness, and (4) patients who were pregnant or lactating.In addition to the implementation of routine nursing methods, the following procedures were used in the intervention group.The management team was organized jointly by the nursing department and the gastrointestinal surgical medical staff. The director of the nursing department and the head nurse for gastrointestinal surgery were in charge. The team had 10 members, including one director of the nursing department, one director and one deputy director of gastrointestinal surgery, one head nurse, and six doctors and nurses. Of these, five had senior professional titles, two had intermediate professional titles, and three had primary professional titles.The director of the nursing department was responsible for supervising the implementation of the project, and the head nurse was in charge of formulating the specific implementation plan and summarizing the data. The charge nurses were responsible for the quality control of the implementation process and the specific implementation of the scheme. Additionally, the charge nurses provided feedback. A weekly feedback meeting was held to solve operational problems promptly and improve the quality of the process.To ensure the scheme's smooth implementation, the team leader organized weekly 30-minute training sessions for the research team members in the form of theoretical teaching, on-site demonstrations, scenario simulations, and group discussions. The training was conducted a total of three times.After the training was completed, theory and operation examinations with a full score of 100 points were organized. A score of ≥85 points indicated that the staff member was qualified to perform the procedure. The pass rate of the entire staff's examinations was 100%.Before the implementation of the scheme, the team leader formulated a scheme implementation management system; they also established a WeChat group to facilitate the timely responses to questions and coordinate the resolution of implementation process problems. Joint team discussions were conducted to formulate the standard procedure for postoperative pain management for patients with perianal abscess as an operational flow chart, which was placed beside the patient’s bed. The responsible nurse implemented the scheme and authorized the relevant pain management according to the procedure.Regular monthly meetings were organized in which the members of the research team, the postoperative pain-management team for patients with perianal abscess, and the scheme implementation personnel discussed and summarized the problems and difficulties occurring in the implementation process to continually optimize the process and enhance its quality control.Previous studies have shown that the level of early postoperative pain catastrophization is higher in patients with hemorrhoids , 12. In Patients in the observation group received routine nursing. For postoperative pain management in patients with perianal abscess, the responsible nurses provided mainly oral bedside health education  to (1) educate patients on the significance of pain management, correctly guide their diet, urination, defecation, and activities, and inform them to take diclofenac sodium sustained-release tablets orally  or (2) use empathy for pain relief.According to the frequency specified by the hospital, the responsible nurses visited the patients' bedsides at 8:00 and 16:00 every day to implement the visual analog scoring method and facial expression scale for patient pain evaluation. These scores, along with the analgesic effect, were recorded in detail. Before dressing changes, the responsible nurses additionally fumigated and washed the wound using TCM to achieve an anti-inflammatory, analgesic, and wound-cleaning effect and arranged routine dressing changes by doctors.(1)Pain control and satisfaction: The Houston Pain Outcome Instrument was used, which was sinicized by Chinese scholar Qu Shen in 2006 and tested for reliability and validity . A study(2)Patient rehabilitation indicators: The patient rehabilitation indicators were wound edema incidence, edema disappearance time, urinary retention, defecation difficulty, and other complications. For the wound edema score, a four-grade scoring method was used : 0 pointThe responsible nurse established the patient's file upon their enrolment in the present study and completed the general patient information according to the patient's medical record. The responsible nurse recorded data during the intervention, and the remaining information was collected by the research team personnel responsible for data collection according to the actual patient evaluation results.The wound edema data included information on the wound edema immediately after operation and at 3, 5, and 7 days after operation; the edema disappearance time was recorded when the patient returned to the hospital for a follow-up one month after the operation. If the patient is discharged 5 to 7 days after surgery, the nurse in charge will guide the patient to evaluate wound edema. To ensure information validity, the research subjects were selected in strict accordance with the standards, and the researchers used unified guidelines during data collection and skillfully implemented the intervention process into the patient's routine.α = 0.05.The statistical data analysis was conducted using SPSS 19.0 software. The count data were expressed as the number of cases and percentage and were compared using an chi-squared test. The measurement data were expressed as mean ± standard deviation (x ± SD) and compared using a t-test. The inspection level was set at From June 2019 to June 2020, 46 patients with perianal abscess in our hospital were included in the observation group. These patients received routine pain management. Between July 2020 and July 2021, 48 patients with perianal abscess were included in the intervention group.n = 46) comprised 30 males and 16 females aged 26–58 years (37.41 ± 5.24 years). The education level was primary school or junior middle school in 16 patients, senior high school or technical secondary school in 19 patients, and junior college or above in 11 patients. The patients' body mass index (BMI) was 18.3–27.6 (24.86 ± 2.15), and the course of the disease was 3–9 days (4.86 ± 1.34 days). The space abscess type was an ischiorectal abscess in 10 cases, a low perianal abscess in 16 cases, a posterior anorectal abscess in 11 cases, and a pelvirectal abscess in 9 cases.The observation group (n = 48) comprised 33 males and 15 females aged 28–29 years (37.69 ± 5.63 years). The education level was primary school or junior middle school in 18 patients, senior high school or technical secondary school in 18 patients, and junior college or above in 12 patients. The patients' BMI was 18.9–27.6 (24.95 ± 2.34), and the course of the disease was 3–10 days (5.12 ± 1.43 days). The space abscess type was an ischiorectal abscess in 10 cases, a low perianal abscess in 15 cases, a posterior anorectal abscess in 12 cases, and a pelvirectal abscess in 11 cases.The intervention group (P > 0.05). Therefore, the two groups were comparable . However, at 3, 5, and 7 days after operation, the wound edema score was better in the intervention group than in the observation group; the differences were statistically significant . The incidences of urinary retention and defecation difficulty were 4.17% (2/48) and 8.33% (4/48), respectively, in the intervention group and 10.87% (5/46) and 19.57% (9/46), respectively, in the observation group; the differences between the two groups were statistically significant   .The peripheral anal canal is innervated mainly by the pudendal nerve from the spinal nerve and is sensitive to pain. Surgical trauma will increase the sensitivity of the central and peripheral nervous system, increase the release of pain-causing substances , and stimulate the pain nerve. Pain is one of the main problems faced by postoperative patients.A previous study  revealedIn the present study, the standard pain-management procedure was formulated based on the clinical practice guidelines of perianal abscess pain management, and self-management and TCM techniques were used during key time periods (defecation and dressing change). The procedure can help understand the key time points of pain health education and encourage and support patients in pain self-management. Furthermore, continuous monitoring, timely analysis, and quality improvement were undertaken to ensure the quality of pain management, thus effectively improving patients' pain outcomes and improving their satisfaction.P < 0.05).The results of the present study revealed that the pain control and satisfaction scores after intervention were significantly better in the intervention group than in the observation group; the differences were statistically significant .The results of the present study revealed that the wound edema score, edema disappearance time, urinary retention, and defecation difficulties after the implementation of the standardized pain-management procedure were better in the intervention group than in the observation group (In the present study, a pain-management team was established to formulate and implement a standardized procedure for postoperative pain management for patients with perianal abscess; this effectively improved the patients’ level of pain and satisfaction and promoted patient rehabilitation. Ultimately, good results were achieved.However, the results may be biased due to the relatively small study sample and the rapid turnover of patients with perianal abscess. Sample size expansion and continuous monitoring are required to further verify and improve the scheme. At the same time, the implementation process of this study focuses on pain management during defecation. The impact of perianal abscess type on postoperative pain was not analyzed. In future work, we will continue to explore appropriate pain evaluation methods and multidimensional evaluation tools for patients with perianal abscess after surgery, further improve the pain-management program, and greatly improve the implications of pain care.


IntroductionDentin hypersensitivity has been defined as a short, sharp pain caused by exposing naked dentin to external stimuli such as evaporation, heat, cold, osmotic liquids, and tactile effects. None of the available treatments has been considered the gold standard in treating dentin hypersensitivity. The use of laser has recently become more popular, and it is a promising treatment method in this field. The study aimed to compare the effectiveness of both 810 nm and 650 nm diode lasers in treating dentin hypersensitivity.Materials and methodsThis study was conducted on six patients who were referred to the Department of Oral Medicine, Faculty of Dental Medicine, Damascus University  with 108 teeth suffering from generalized dentin hypersensitivity and were randomly divided into two groups. Group 1 consisted of three patients with 50 teeth treated with an 810 nm diode laser; it was divided by the split-mouth design into two subgroups. The first subgroup was treated by the application of the laser alone toward the target area with 1-watt power, continuous mode, and a total application time of 90 seconds, and the second subgroup was treated by applying sodium fluoride gel for one minute, then the laser was applied with the same settings as the first subgroup. Group 2 consisted of three patients with 58 teeth treated with a 650 nm diode laser; it was divided by the split-mouth design into two subgroups. The first subgroup was treated by the application of the laser alone toward the target area with 200 m watt power, continuous mode, and a total application time of 120 seconds, and the second subgroup was treated by applying sodium fluoride gel for one minute and then applying the laser with the same settings as the first subgroup. The pain was evaluated using a numeric rating scale (NRS) of 100 degrees before and immediately after treatment, and then after three to six and nine months by applying an air stream from a dental chair syringe at a distance of 0.5 cm from the target area.ResultsThis study showed that both types of lasers were effective in treating pain caused by dentinal hypersensitivity. The average values of pain reduction on the NRS showed the superiority of the 810 nm diode laser over the 650 nm after treatment and at all time points of pain assessment. No statistically significant differences were detected between applying laser alone and applying it combined with sodium fluoride gel in pain reduction values.ConclusionsThe application of an 810 nm diode laser either alone or in combination with sodium fluoride gel in treating dentin hypersensitivity is effective and better than the application of a 650 nm diode laser either alone or in combination with sodium fluoride gel. In addition, applying a 650 nm diode laser either alone or in combination with sodium fluoride gel has slight effectiveness in treating dentine hypersensitivity, and it is believed that a single treatment session with a 650 nm diode laser was not enough to obtain the required pain reduction. Dentinal hypersensitivity (DH) is defined as a sharp, short pain that appears after exposing the exposed dentin to external stimuli, e.g., evaporative, thermal, lytic, or tactile stimuli. This pain cannot be attributed to other dental lesions or diseases . DH causThe number of people with dentin hypersensitivity has increased in recent decades. A systematic review by Zeola and his colleagues of 77 worldwide studies about the prevalence of DH in 2019 has revealed that the mean prevalence of DH among the reviewed studies was 33.5% [The pain of DH has been explained based on many theories. The hydrodynamic theory is considered one of the most acceptable theories for most researchers in this field. Its interpretation of pain depends on the movement of fluids inside dentinal tubules, either inwards or outwards of the pulp. This theory was presented by Brannström . It assuThe reasons for DH are the following: First, the exposed dentine, which is called localization. The second reason is the opening of the dentinal tubules directly connected to the pulp, called initiation . The expDH can be controlled by either an at-home treatment modality, as it depends on the patient such as using toothpaste containing fluoride, strontium, and oxalate, or by an in-office treatment modality under the supervision of the dentist who has a wide range of products that can be applied to treat DH such as varnishes, resin-based materials and lasers . In manyIn 1935, scientist Grossman suggested several conditions that must be met in the ideal treatment of dentin hypersensitivity .With the insertion of medical laser devices in various fields of dentistry, the first laser was used in the mid-sixties to remove dental necrosis. However, the first time laser was applied in the treatment of DH was in the mid-eighties by Matsumoto and his colleagues .Compared to other methods of treating DH, the use of laser is an easy-to-apply, safe and reliable method, in addition to having an immediate effect ,13.The recent great development of the laser industry, especially in multi-wavelength diode lasers, and their widespread availability make them the best choice for most dentists. These devices are characterized by their small size and ease of use, movement, and operation through modern interactive interfaces. Several systematic reviews have concluded that diode and near-infrared lasers have been effective in treating DH ,15.After reviewing the medical literature, systematic reviews suggested that it is necessary to design more randomized controlled trials with long follow-up periods to ensure the therapeutic effect of the laser on DH ,17. it wStudy sampleThis was a single-blind, randomized clinical trial with a split-mouth design. This study was conducted after getting approval from the Scientific Research Ethics Committee at the Faculty of Dentistry, Damascus University (UDDS-834-03092019/SRC-1450), and was funded by the Damascus University Postgraduate Research Budget. The sample included six patients  suffering from generalized DH; their ages ranged between 20 and 30 years. The sample was collected from patients visiting the Department of Oral Medicine at the Faculty of Dentistry, Damascus University, Syrian Arab Republic from 6/1/2020 to 12/31/2021. Patients were accepted after they were provided with all information related to the research (the method of conducting this study and the follow-up period) in a written form, and all of their questions were answered orally. After that, written consent to enter this research was taken.Study groupsThe sample size was determined using the G power program , and depending on the mean and standard deviation in the study of Naghsh and his colleagues . After aPatients included in the study were divided randomly into two main groups by drawing a card with a hidden number from a box without knowing the meaning of the number that appeared.Inclusion criteriaPatients were selected according to the following inclusion criteria: patient age range 18 to 30 years, with good general health and did not suffer from any general or chronic diseases, presenting with at least one tooth with DH on each side of the upper or lower jaw. The pain intensity of the tooth with DH was 30 or higher on the NRS numeric rating scale, and the area of DH was the vestibular or lingual surfaces of the incisors, canines, and upper and lower premolars.Exclusion criteriaPatients were excluded according to the following criteria: patients undergoing periodontal treatment one month prior to the study, periodontal surgery three months prior to the study, and fixed orthodontic treatment. Exclusion criteria also comprised patients consuming anti-inflammatory drugs, analgesics, and sedatives 72 hours before laser application. After examining the patient, molars and all teeth that were decayed, broken, cracked, having birth defects in enamel or dentin, restoratively treated, crowned, used as abutments, or showing symptoms of irreversible pulpitis, were excluded from the studied sample. Ethyl chloride was used to test the vitality of the teeth and to exclude teeth showing symptoms of irreversible pulpitis.Group 1: 810 nm Diode Laser GroupThe number of teeth in this group was 60, and after applying the inclusion and exclusion criteria, the number decreased to 50 teeth treated with an 810 nm diode laser, , 1-watt power, continuous mode, and a total application time of 90 seconds.By using the split-mouth design, this group was divided into two subgroups.The first subgroup was the right-handed split of the upper/lower jaw and included 25 teeth suffering from DH, which were treated using an 810 nm diode laser alone. The second subgroup was the left-handed split of the upper/lower jaw and included 25 teeth suffering from DH, which were treated by applying sodium fluoride gel to the area of DH. Then, the laser was applied with the same settings as the first subgroup.Group 2: 650 nm Diode Laser GroupThe number of teeth in this group was also 60, and after applying the inclusion and exclusion criteria, the number decreased to 58 teeth treated with a 650 nm diode laser , 200 m watt power, continuous mode, and a total application time of 120 seconds.By using the split-mouth design, this group was divided into two subgroups.The first subgroup was the right-handed split of the upper/lower jaw and included 29 teeth suffering from DH, which were treated by applying a 650 nm diode laser beam alone. The second subgroup was the left-handed split of the upper/lower jaw and included 29 teeth suffering from DH, which were treated by applying sodium fluoride gel to the area of DH. Then, the laser was applied with the same settings as the first subgroup.Pain assessmentThe numeric rating scale NRS was used to assess pain. It consists of 100 degrees. The method of measuring pain was explained to each patient. Each patient was asked to respond verbally about the value of the pain she/he felt. The response was determined following the scale displayed in front of the patient, in which the number 0 indicates no pain at all, and the number 100 indicates very severe and unbearable pain, mild pain ranges from 1 to 30, moderate pain is greater than 30 to 60, and severe pain is greater than 60  was used to assess the degree of pain in teeth in addition to dentin hypersensitivity. This was done by applying a continuous air stream for three seconds from the air syringe in the dental chair, directly on the tooth's surface that suffers from DH and a distance of about 0.5 cm. The temperature of the air stream was similar to the room temperature and the average was 25°C at all time points of pain assessment, and this temperature was stable all the time and controlled by the room AC, which was set up at the same degree (25°).Patients were also emphasized that it was necessary to follow oral health procedures by brushing their teeth daily (at least twice) with a medium-hard toothbrush without using any special pastes to treat DH and avoiding whitening toothpaste during treatment follow-up periods.Clinical proceduresAll clinical procedures were done by one researcher, and only the patient was blinded.Teeth were isolated using a cotton roll in the vestibular gutter, and the DH area was dried with a small cotton ball. An air stream from the air syringe of the dental chair was applied perpendicular to the vestibular surface for three seconds. The pain value given by the patient was recorded immediately prior to treatment.After that, the laser was applied in each of the two study groups according to the following:810 nm Diode Laser GroupThe first subgroup was treated by applying a diode laser beam of 810 nm in a continuous mode with a power of 1 watt for 30 seconds. The application was perpendicular to the tooth's surface and at a distance of 2 mm by means of an optical fiber with a diameter of 320 micrometers. Thus, the entire area of DH was slowly scanned. The application was repeated three times with an interval of 30 seconds between each application. The total application time was 90 seconds. The second subgroup was treated by applying sodium fluoride gel to the area of DH with a small brush and left for one minute. Then, the extra gel was removed with a small cotton ball. After that, the laser was applied with the same settings used in the first category  at a room temperature of 25°C, and the pain value given by the patient was recorded.Follow-up periods: The pain was re-assessed after three months, six months, and nine months.Statistical studyData were collected and entered into a Microsoft Excel sheet . They were analyzed statistically using SPSS® version 26.0 , with a significance level of 0.05.Independent samples' student t-tests were used to study the effects of the type of laser used and sodium fluoride gel application on the amount of pain reduction according to the NRS.The study sample included six patients  with 108 teeth suffering from dentin hypersensitivity according to the 100-degree numeric rating scale. There were fifty teeth in three patients  in the 810 nm diode laser group; teeth were 23 upper (5 premolars and 18 incisors) and 27 lower (9 premolars and 18 incisors). In 58 teeth in three patients  in the 650 nm diode laser group, teeth were 30 upper (11 premolars and 19 incisors) and 28 lower (9 premolars and 19 incisors) . The average pain reduction was 6.9 ± 27 and 5.8 ± 30.4 when applying the laser alone and after sodium fluoride gel, respectively.Dentin hypersensitivity is a serious challenge for many people and significantly affects their quality of life. It often forces them to change their daily habits such as eating, drinking, talking, and even brushing their teeth. Severe degrees of DH that last long periods may lead to psychological and emotional harm .The global prevalence of DH ranges between 3% and 98%. This wide range is due to the different areas studied and the inclusion and diagnostic criteria applied in each study. In addition, it is ascribed to the different health and nutritional habits prevalent in a region . The numThe participants' ages in this study ranged between 20 - 30 years. The split-mouth design was used, and the evaporative stimulator was used as an external stimulus for pain assessment. This protocol is consistent with the recommendations of the systematic review by Marto and his colleagues , as thisAccording to many previous studies, the current study adopted the teeth as the main research unit in the sample ,21, in cThe current study aimed to evaluate the effectiveness of the two lasers in reducing DH pain. The results showed that both types of laser contributed to reducing pain immediately after treatment, and the decrease continued during all observation periods. According to the literature, the immediate effect of both lasers can be attributed to their direct effect on the non-myelinated fibers (C) within the dental pulp. The laser depolarizes the nerve endings of these fibers and raises the pain threshold by activating the sodium-potassium pump within the cell membrane of these nerve endings . Some stThe results of the current study showed that the application of the 810 nm diode laser according to the following settings  contributed effectively to the reduction of pain caused by DH immediately after treatment. The reduction continued during the follow-up periods, which extended to nine months. These results are consistent with the study by Hashim and his colleagues , in whicAs for the 650 nm diode laser, the results of the current study showed that it reduced pain levels immediately after treatment, and the reduction continued during follow-up periods of up to nine months. However, this decrease was slight, as it did not exceed 10 degrees on the NRS of 100 degrees. On the other hand, in the study conducted by Dilsiz and his colleagues, in which a 685 nm diode laser was used with an output power of 25 mW and a frequency of 10 Hz for 100 seconds; the results showed that the previous laser was effective in reducing pain by 4 degrees of the 10-point visual analog (VAS) pain scale . This diThe current study showed the superiority of the combined application of both types of lasers with sodium fluoride gel over the application of laser alone. However, there were no statistically significant differences in the 650 nm diode laser group. Nonetheless, by observing the pain reduction averages and the differences between them in Table Study limitationsIn this study, teeth were considered the main unit in the studied sample, and since pain is a personal criterion that differs from one person to another, it was considered one of the most critical limitations of this study. In addition, there was no control group to control the results and exclude the placebo effect. That leads to proposing designs for future studies that consider persons - not teeth - as the main unit in the research sample, with a negative control group to control the results.Based on the results of this study, it can be concluded that the effectiveness of applying the 810 nm diode laser alone and in combination with sodium fluoride gel to treat dentine hypersensitivity was better than the application of the 650 nm diode laser alone and in combination with sodium fluoride gel. Moreover, the combined technique resulted in higher pain reduction than the application of the 810 nm diode laser alone.On the other hand, the application of the 650 nm diode laser alone and in combination with sodium fluoride gel had slight effectiveness in treating dentine hypersensitivity. In addition, the combined technique resulted in higher pain reduction than the application of this laser alone, even though there were no statistically significant differences between the two application methods, and it is believed that the single treatment session with the 650nm diode laser was not enough to obtain the required pain reduction.