BackgroundChronic low back pain (CLBP) is one of the most common complaints affecting the population worldwide including in Lebanon. Until 15 years ago, surgery was the treatment of choice. However, conservative measures are now preferred because of the large number of post-surgical complications, in addition to the many conditions where surgery cannot be performed.ObjectiveThe aim of our study is to determine the effectiveness of transformational epidural injection of ozone (TFEOI) in the management of CLBP among the Lebanese population in the Nabatieh area in comparison with patients who received transformational epidural steroid injection (TFESI).MethodsA one-year (2016-2017) retrospective study where 100 patients with CLBP were selected from two hospitals  and divided into two groups. Fifty patients were treated with Ozone injections while the other 50 were treated with steroid injections. For each patient, we recorded the type of pain, irradiation, paresthesia, and the type of injection given (steroid or Ozone). We used the patients' files and contacted them via phone calls. The results of this study were reached based on Vas Score and Mac Nab criteria which are subjective questionnaires.ResultsThe study showed that the TFESI was effective for a short duration . On the other hand, TFEOI was effective over both short and long duration .ConclusionResults from this study provide that ozone injection has high benefits in the management of CLBP in the Lebanese population. General presentationLower back pain with or without sciatic nerve involvement affects roughly 80% of the population at least once in their lifetime . AccordiChronic low back pain is an increasing problem worldwide. Many studies performed in USA and China showed that back and spine impairments were more common in women. Differences in acute presentation, management, or outcome have important medical and economic implications. A high body mass index and a lack of physical activity are both risk factors for back pain in a world where obesity and overweight have increased by 28% since the year 1980 in adults .Definition of chronic low back painChronic low back pain (LBP) is a common disorder involving the muscles, nerves, and bones of the back for more than three months. Pain can vary from a sudden sharp feeling to a dull, constant ache. Presentation differs according to the cause, so properly identifying and describing symptoms leads to more accurate diagnoses. Patients complain of a combination or a single symptom of the following: dull pain, referred pain to the buttocks, legs, and feet, and pain worsening after prolonged sitting. Pain that improves within six weeks with or without conservative treatment is considered acute while chronic pain persists for more than three months (7-12 weeks) ,5.There are no specific characteristics that confirm or ignore the diagnosis of discitis in lower back pain . More tyIn the physical exam, most of the time there are not any typical characteristics of discogenic pain. Biphasic straightening from flexion is considered by some to be an indication of a disc complaint. Pain that radiates to the toes unilaterally or bilaterally is considered characteristic of discogenic low back pain. Vanharanta has described the pain radiating from the disc due to provocation with a tuning fork pressed on the processus spinosus of the affected segment . AlthougChronic lower back pain origins may include injury, diseases, or prolonged stress on a specific part of the body . CLBP maNoninvasive imaging along with a good clinical examination  should be enough to identify or rule out underlying disease processes , neurological disorders requiring surgical intervention , and psychological distress that may amplify or prolong the pain . In patiManagement of chronic low back painDifferent ways of treatment may be used in the management of chronic lower back pain. They include conservative nonpharmacologic treatment (physiotherapy), and pharmacologic treatment , and for those with severe functional disabilities, radicular symptoms, or refractory pain, epidural therapeutic injections or even surgery may be preferred .Conservative TreatmentPatients commonly use conservative treatment options with or without consulting the physician. Nonpharmacologic conservative treatment includes exercise therapy (focusing on strengthening core muscles), behavior therapy (relaxation), and acupuncture massage . AcetamiSurgerySurgery can be considered in patients with anatomic abnormalities consistent with the distribution of pain and patients with significant functional disabilities not improving even by nonsurgical treatments. Spinal fusion is used in treating back pain caused by fractures .Epidural Therapeutic InjectionsThey include Ozone and steroids injection. Both techniques were found to have benefits for lower back pain . Ozone  that activates the molecules of diatomic oxygen in a voltaic arch . UltraviSteroids are known to have an anti-inflammatory function. Steroid infiltration relieves the peri-ganglionic inflammation by ensuring recovery of the normal ganglio-neural myelin sheath, and hence nerve function, at the disease site . During The procedure of injection of OzoneEvery patient will receive local anesthesia before the injection to avoid any pain. Then the patient lies with a pillow under his abdomen to correct lumber lordosis. This maneuver makes the lumber disc area approach to the base of the superior facet of the inferior vertebra, then the neurosurgeon uses a 15 cm long, 22 G spinal needle by directing it into the disc space at an angle of 50-60⁰ approximately. The angle can be obtained by oblique views. When the annulus is reached, the surgeon should twiddle a gritty feel of the annulus. Then the needle is pushed up to the center of the disc (nucleus pulposus) then with verifying the position with anterior, posterior, and lateral imaging. The tip of the needle should be in line with the spinous process and medial to the most medial aspect of the pedicle. The discography is done by using water-soluble contrast to confirm the needle position. When the disc is pathological, the dye spreads all along up to the canal and when the disc is normal, the dye remains in the center. Once confirmed, 5-7cc of 27-40mcg of epidural oxygen-ozone gas is injected into the disc space. The distraction of the space and whitish visualization of gas on the screen confirms the presence of gas in the disc space. The needle is removed, then a sterile dressing of the injection site should be done. The procedure lasts for approximately 20 to 30 mins and the patient is discharged home within two hours ,27.Studies on chronic low back painWomen complain of lower back pain more than men do. This is probably due to their higher responsibilities as workers in addition to spending longer duration in household work and children care . A recenOne hundred fifty-nine patients  were included and were randomly assigned to two groups. Seventy-seven patients (group A) underwent intradiscal and intraforaminal injections of a steroid and an anesthetic, and 82 patients (group B) underwent the same treatment with the addition of Ozone. An Oswestry Low Back Pain Disability Questionnaire was administered before treatment and at several intervals, the last being at a six-month follow-up. Results were compared with the X2 test. The results showed that the intraforaminal and intradiscal injections of a steroid plus Ozone are more effective at six months than injections of only a steroid in the same sites .Comparative studies between Ozone and steroidAndreula Cosma and collaborators 2003 did a randomized control trial in Italy on 600 patients with lumbar disc herniation treated with a single session of Ozone therapy. All patients presented with clinical signs of lumbar disk nerve root compression with CT and/or MRI evidence of contained disk herniation. They randomized patients into two groups of 300 each. Group A received 4 mL intradiscal and 8 mL periganglionic Ozone at 27 µg/mL concentration. Group B received Ozone in a similar concentration plus steroid (1 mL Depo-Medrol 40 mg/mL) and 0.5% marcine. The outcome was assessed using modified Mac Nab criteria. Treatment was successful in 211 (70.3%) patients with excellent in 160 and good in 75 patients (p < 0.05). They concluded that Ozone therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management and has a significant cumulative effect .Shah et al. elaborated on a prospective study that was set up from 2006 to 2008. Patients with contained discs on MRI and failed conservative trials were included in the study. Those with cauda equina syndrome or spinal tumors or infections in addition to pregnant women were excluded. A total of 93 patients were injected with intra-discal ozone. There were 34 females and 59 males with an average age of 54±13.2 years (range 32 to 78). Fifty-one patients had two-level lesions while 24 had three-level lesions. Only 18 had single-level discs. Eleven patients had both sensorimotor deficits while six had only sensory and two had only motor deficits. The remaining patients had no neurological deficit. Eleven of these patients had previous open laminectomies done (failed back) .Greenough and Fraser's score was used to study the outcome. The results showed that the mean follow-up was 27.86±3.25 months. The preoperative Greenough and Fraser score improved from a mean of 24.33±5.94 (12 to 45) to a postoperative  mean of 68.36±6.24 (50 to 75) (p < 0.001). Twenty patients had good results while 66 had excellent results according to Greenough and Fraser's score. Four patients did not follow up. Three patients had to undergo surgery in form of microdiscectomy. nine out of 13 patients with motor deficits had significant recovery (≥grade 4 power) while only three out of 17 having sensory symptoms continued to have sensory symptoms. Five patients in this series had post-operative headaches and were treated conservatively. There were no cases of infection. This study reports the successful treatment of contained lumbar disc herniation using intradiscal Ozone. However, a comparative and controlled trial will be essential to firmly establish this modality .A study was done from June 2000 to December 2006 on the use of Ozone injection using a minimally invasive percutaneous technique for the treatment of lumbar disk herniation. The study was performed on 2,900 patients affected by lumbar disk herniation. Patients were selected on the basis of clinical, psychological, neurological, and neuro-radiological criteria. Exclusion criteria were extruded hernia and/or free disc fragments, hyperalgesia paralyzing sciatica, and progressive neurological impairment of the affected limb ,31.All patients were evaluated after one month, and those showing only partial success were scheduled for a second treatment session. The study’s results were evaluated with the modified Mac Nab classification, the visual analog scale (VAS), and the Oswestry Disability index at six and 12 months. Success rates were 75% to 80% for soft disc herniation, 70% for multiple disc herniation, and 55% for failed back surgery syndrome. None of the patients suffered early or late neurological or infectious complications. Based on these results, the researchers concluded that minimally invasive percutaneous treatment by Ozone infiltration is a valuable and competitive technique that provides excellent results at low cost and without complications .ObjectivesPrevious studies and data analysis have demonstrated a considerable risk of failure and complications in both conservative and surgical treatment of chronic lower back pain, which raises concerns about seeking other treatment modalities with higher efficacy, less complication, and less risk of failure. In this study, we aim to evaluate the effectiveness of TFEO injection as an alternative treatment modality for patients with chronic lower back pain in the Lebanese population.Primary ObjectiveThe primary objective of our study is to determine the efficacy of TFEOI injection in the management of back pain in the NABATIEH area.Secondary ObjectivesWe aimed to compare the results with the patients who received steroids injection, the results among the locations of radiculopathy, and the results among male and female patients.Study designThis is a retrospective study targeting patients with CLBP who received a TFEOI or a TFESI in Al-Najdah and Sheikh Ragheb Harb hospitals in Lebanon in the area of Nabatieh. The duration of the study was from January 2016 to January 2017 (one year). In this study, we will compare the improvement in results between Ozone or steroid injections at three-time intervals .Subjects and study populationOne hundred patient files were randomly chosen from the files present in the two specified hospitals. All patients were diagnosed with CLBP 7-12 weeks) by clinical symptoms and MRI or CT-scan images. The patients were categorized according to the type of sciatica and they were divided into two groups: 50% (50 patients) were treated by transforaminal epidural ozone injection , and 50% (50 patients) received transforaminal epidural steroids injection. In Table 2 weeks bData collectionFor each patient, information was collected from their file about their name, age, gender, paresthesia’s disk, radiculopathy, presence of numbness, results of CT or MRI, and whether they received an Ozone or steroids injection and their clinical improvement after injection at one month, three months, and six months. The VAS score for pain and Mac Nab criteria were used in the assessment of pain based on questions. Each patient received a phone call asking them about their symptoms before and after the injection of ozone and steroids.VAS ScoreVAS  for pain is a measurement instrument for subjective characteristics or attitudes that cannot be directly measured. It’s a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually, 10 cm (100mm) in length, anchored by two verbal descriptors, one for each symptom extreme, “no pain” (score of 0) and “pain as bad as it could be” or “worst imaginable pain” score of 10 . It is dMac Nab modified CriteriaMac Nab scale is used to determine the outcome assessment of patient satisfaction after ozone or steroids injection therapy . The staData statistical analysisFor data entry and analysis, we used the statistical package for social sciences for windows version 22 . Independent samples t-test was used to test statistical significance. Descriptive analysis of quantitative variables will be presented as mean, standard deviation, minimum and maximum values. In addition, the software will also comprise the frequency and percentage of each category of patients. The number of missing values will be reported for each variable if present. A two-sided P-value of 0.05 was considered to be statistically significant.Numbers of females and males who had both types of injectionsFifty-eight patients of the total patients were females, and 42 patients were males. The mean age equals 49.86±12.664 years. The total number of patients is 100 patients, and the age range is 26-72 years  to assess whether the effect of steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference after one month where the p-value = 0.072 > 0.05 and after three months the p-value = 0.672 > 0.05 from the injection between Ozone and Steroids. However, there was a significant difference after six months of injecting (p =0.001 < 0.05) between results according to VAS score after six months of injection between female patients who had ozone injections and who had steroid injections Table .Results of VAS score before and after one, three, and six months of injection of steroids and ozone in male patientsWe evaluated the number of male patients with different VAS score before and after one, three, and six months of injection of steroids and ozone Figure .VAS Score Results Before Injection of Steroids and OzoneFigures Results After One Month of Steroids Versus Ozone InjectionFigures Results After Three Months of Steroids Versus Ozone InjectionFigures Results After Six Months of Steroids Versus Ozone InjectionFigures Results Significance for Male Patients for Both Types of Injection After One, Three, and Six MonthsWe conducted an independent samples t-test  to assess whether the effect of steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference according to the VAS score scale after one month between the male patients who had steroids injection and the male patients who had ozone injections p= 0.321 > 0.05, and after three months for the same male patients with the type of the same injection with p-value = 0.344 > 0.05. But there is a significant difference in the results between the male patients who had steroids injection and the other males who had ozone injections with p-value = 0.042 < 0.05 after six months of injections  to assess whether the effect of steroid injection differed significantly from Ozone injection according to Mac Nab criteria after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference after one month between the results with female patients who had steroids injection in comparison with the female patients who had Ozone injection with p-value = 0.304 > 0.05, and the same after three months from the injection between Ozone and Steroids between the same female patients with the same type of injections with p-value =0.738 > 0.05, however, there was a significant difference after 6-months of injecting between the results in female patients who had ozone injections and the others females who had steroids injections with p-value =0.008 < 0.05  to assess whether the effect of Steroid injection differed significantly from Ozone injection after one month, three months, and six months. The assumptions of normality and equal variances were evaluated with no violations noted. There was no significant difference according to Mac Nab criteria after one month between the male patients who had steroids injection and the male patients who had ozone injections p= 0.688 >0.05, and after three months for the same male patients with the type of the same injection with p-value= 0.630>0.05. But there is a significant difference in the results among the male patients who had steroids injection and the other males who had ozone injection with p-value=0.002 <0.05 after six months of injection  before injection, become with the same VAS score (0-1) after one, three, and six months of ozone injection  before ozone injection, after one, three months, the results one male patient had a VAS score of (1-2), and after six months the results showed one male patient who had VAS score (2-3) Table .Table On the other side of the same table, the results showed the results for five females with L4 radiculopathy who had ozone injections. The results were two females with a VAS score (6-7), two female patients with a VAS score (7-8), and only one female patient with a VAS score (8-9) before injection. The results after one month were one female patient with a VAS score (0-1), one female patient with a VAS score (1-2), and 2 female patients with a VAS score (2-3). After three months of ozone injection. Only one female patient had a VAS score of (0-1), another female patient had a VAS score of (1-2), 2 female patients had a VAS score of (2-3), and one female patient had a VAS score of (8-9). After six months the results were one female patient had a VAS score of (0-1), 3 female patients had (2-3), and one female patient had a VAS score of (8-9).Table Table Table The total number of male patients with S1 radiculopathy who had ozone injections is 13 patients. The results showed 2 male patients with a VAS score of (5-6), five male patients had a VAS score of (6-7), five male patients with a VAS score of (7-8), and only one male patient had a VAS score of (8-9) before ozone injection. After one month the results were nine male patients had a VAS score of (0-1), three male patients had a VAS score of (1-2), and one male patient had a VAS score of (8-9). After three months the results showed four male patients with of (0- 1), eight male patients had of (1-2), and only one male patient had a VAS score of (8-9). After six months of ozone injection, the results were three male patients with a VAS score of (0-1), six male patients had a VAS score of (1-2), and three male patients had a VAS score of (2-3), and only one male patient had VAS score of (8- 9) , one female patient with a VAS score of (6-7), four female patients had (7-8), and three female patients had a VAS score of (8-9). The results after one month were eight female patients with a VAS score of (0-1), two female patients had a VAS score of (1-2), and only one female patient had a VAS score of (8-9). After three months of ozone injection the results were three female patients had a VAS score of (0-1), five female patients had a VAS score of (1-2), two female patients had (2-3) and only one female patient had a VAS score of (8-9). After six months the results were three female patients had a VAS score of (0-1), three female patients had (1-2), four female patients had a VAS score of (2-3), and only one female patient had a VAS score of (8-9) Table .The objective of our study is to assess the benefit of Ozone in comparison with Steroids in CLBP in the short and long term based on Vas score and Mac Nab criteria, both of which are subjective questionnaires. According to our study, 58% of the total number of patients were females and the other 42% were males. This difference between the two genders may be due to females having a lower threshold of perception of pain and differ in reaction to it . In addiThe objective of our study was to compare the results of injecting either Ozone or steroids as a treatment for CLBP. In the female group, there was no significant difference in the results after one and three months using VAS score  between steroids and Ozone injections. However, after six months of treatment, there was a significant difference with a p value= 0.001 in females treated with Ozone. Using Mac Nab criteria in the female group, we got the same results as in using the Vas score, i.e., no significant difference was seen after one and three months but with excellent and good results with a significant difference after six months  in those into whom Ozone was injected.The same results were observed in the male group where no significant difference was seen after one and three months using both Vas score  and Mac Nab criteria. After six months of treatment, a significant difference was observed in this group when using the VAS score  and excellent and good results with a p value=0.002 using Mac Nab criteria in the Ozone group. This difference in results between the beneficial effect of steroids and the effect of ozone in the short and long term may be due to the anti-inflammatory effect of TFESI that works on the nerve, and hence its function at the disease site . This isThe TFEOI works on localized oxygenation and analgesia. Ozone is also important to muscle relaxation and vasodilation as well as reactivation of muscle metabolism, by favoring oxidation of lactate, neutralization of acidosis, enhanced synthesis of adenosine triphosphate, Ca2+ reuptake, and edema reabsorption. Moreover, a further analgesic effect may be derived from the induction of antioxidant enzymes . This maIn a study about the efficacy of TFESI in comparison to epidural Ozone injection, Joel et al. concluded that TFESI is beneficial in the short term and was not as effective in the long term. On the other hand, Ozone was found to be very safe, cheap, and effective as a short-term and long-term solution for patients with back pain along with sciatic nerve pain . M.GalluStudy limitationsMost of the limitations in this study were due to it being a retrospective study. Most of the data were collected from medical files recorded in a subjective manner with many variables missing . We did not have the privilege to evaluate real-time imaging examinations. Instead, we examined the previously performed radiological images that were available on the computer system at both sites. We were unable to calculate the incidence of CLBP and lacked follow-up with patients. In addition, the number of new cases was not clear.Study perspectivesMore studies are needed to assess the role of Ozone in treating chronic lower back pain in patients in order to observe if any complication would occur if we increased the number of patients. More retrospective and prospective studies are needed to test whether Ozone injection is better used in the management of chronic lower back pain or if there is another drug that may be of more benefit. They should focus on the causes that drive some Lebanese neurosurgeons to go to surgery quickly when they see a patient with back pain for the first time. Is it their experience? Is it pharmaceutical companies? Is it the government policies? Or it is just related to the patient’s social status? It is important to focus on risk factors of chronic low back pain, and the role of sports and physiotherapy in improving the quality of life, and in decreasing the percentage of people suffering from this medical condition.We studied patient profiles of males and females with chronic lower back pain in the Nabatieh area who were treated with either steroids or Ozone injections. According to our study results, the percentage of excellent and good outcomes after one month was approximately the same for both types of injections. Steroids were more beneficial in the short term (1-3 months). Ozone was more beneficial in the long term (six months). Studying patients with different types of radiculopathies, we found that Ozone was better than steroids over both short and long-term durations. These results give us a good plan for the management of increasing morbidity in Lebanese patients. We hope for more studies on the matter to assess the safety of this treatment on a larger scale.


Furthermore, the SB group without other OFPHs and PHs did not show a significantly higher risk of TMD symptoms than the non-SB group. Diurnal clenching and bad posture also affect the stomatognathic system, causing pain or fatigue; however, it did not result in TMDs in patients without any OPFHs and PHs. This implies that OPFHs and PHs may increase the risk of TMD symptoms in coexistence with other habits.Temporomandibular disorders (TMDs) are a multifactorial joint disease of the masticatory system. The possible etiological factors involved in the onset and progression of TMDs include oral parafunctional habits (OPFHs) and postural habits (PHs). However, little information is available on the association between OPFHs and PHs and a predisposition to TMDs. Thus, to investigate whether the presence of OPFH and PH predisposes individuals to TMDs, a survey-based cross-sectional cohort study of self-reported TMD was performed. A total of 2292 patients with TMD were recruited for the survey. Through one-to-one propensity score matching, 166 patients with and without sleep bruxism (SB) were selected. The SB group had a significantly higher risk of masticatory muscular pain or fatigue than the non-SB group ( Temporomandibular disorders (TMDs) are a collective term used to describe pain and functional disturbance of the masticatory system ,2. MastiAccording to the Diagnostic Criteria for TMD (DC/TMD) Axis I, TMDs can be divided into pain-related TMDs including masticatory muscle disorders and arthralgia, and intra-articular disorder including disc displacement with or without reduction and mouth opening limitation and osteoarthritis . EpidemiNumerous factors can be considered in the etiology of TMDs. Oral parafunctional habits (OPFHs), such as bruxism, diurnal clenching, and thumb sucking, are common and usually have negligible effects on the stomatognathic apparatus . Sleep bThus, to investigate whether the presence of OPFH and PH predisposes to TMDs, we performed a survey-based cross-sectional cohort study of self-reported TMD among outpatients who visited the Temporomandibular Joint Clinic of Tokushima University Hospital. We aimed to assess the prevalence of self-reported subjective symptoms indicative of TMD and their correlation with OPFHs and PHs associated with the onset and progression of TMDs.Outpatients with the chief complaint of TMD symptoms who visited the Temporomandibular Joint Clinic at Tokushima University Hospital between April 2010 and September 2021 were recruited. The inclusion criteria for the patients were age >12 years and at least one TMD symptom according to the DC/TMD . The excThe Ethics Committee of Tokushima University Hospital approved the study, and written informed consent was obtained from each patient after sufficient explanation of the research purposes (No. 2279-4).All participants were asked to fill out a unique self-reported questionnaire, including items on TMD symptoms, general and oral health, OPFHs and PHs, and some sociodemographic issues. The answer alternatives to all questions were “yes” or “no”, except for items 9 and 14 . All patThe clinical outcomes were set as the present TMD symptoms, which included “TMJ pain during various mandibular movements (item 1)”, “masticatory muscle pain and fatigue (item 2)”, “difficulty in mouth opening (item 3)”, “TMJ sounds, such as clicking or popping (item 4)”, “frequent headaches and stiff shoulder (item 5)”, and “joint luxation (item 6)” from answers of alternatively self-reported questionnaires.In the present study, the estimated propensity score of each patient was used to perform individual matching analysis to determine whether OPFH and PH were present. Statistical analysis was performed using SPSS 27.0 . To calculate the propensity score, a logistic regression model was fitted for each symptom and the patients’ constitution, including age, sex, habits, and history. To evaluate the effect of OPFH and PH on TMD symptoms, the estimated propensity score is required to calculate C-statistics, which is represented by the area under the receiver operating characteristic (ROC) curve and is an indicator for evaluating the goodness of fit . Each paFisher’s exact test was used to compare the six present TMD symptoms between the groups with and without OPFHs and PHs. Logistic regression analysis for each TMD symptom was performed in propensity-matched patients to analyze the odds ratios and 95% confidence intervals with reference to the absence of OPFHs and PHs. The two VAS scales for pain and daily hindrance were compared between the presence and absence of each habit using the Mann–Whitney U test. In the present study, two different methods were used to analyze the effect of OPFHs and PHs: (1) all items, including other OPFHs and PHs except for targeted habits were used, and (2) patients without other OPFHs and PHs were selected to investigate the effect of targeted habits on the onset and progression of TMD symptoms. Of 2367 outpatients, 2292 patients with TMD  were recruited for the survey using the self-reported questionnaire . The remTo examine whether SB affects TMD symptoms, patients without other OPFHs and PHs were included . A totalp = 0.018), including medical history, OPFHs, and PHs. However, the degree of maximum pain of daily hindrance did not differ significantly between the SB and non-SB groups, regardless of masticatory muscle pain or fatigue. Furthermore, the SB group without other OFPHs and PHs showed no significantly higher risk of TMD symptoms than the non-SB group (SB group .p = 0.015), masticatory pain or fatigue , and headache or shoulder stiffness  than the non-DC group . However, patients with TMD without other OPFHs and PHs, except for DC, showed no significantly higher risk of TMD symptoms (p < 0.001) than the non-BP group (p = 0.007) than the non-BP group (For other OFPHs or PHs except SB, the demographic and clinical characteristics of TMD patients with and without DC, CH, FD, or BP were evaluated . Before DC group . Furthersymptoms . The BP BP group . FurtherBP group . HoweverBP group .Numerous epidemiological surveys of TMD have been designed and reported previously ,29,30,31The present study showed that SB affected pain or fatigue of the masticatory muscles, and DC affected jaw pain, pain or fatigue of the masticatory muscles , and heaThe following considerations and limitations of the present cohort survey should be addressed. First, as this cohort survey was performed using a propensity score-matched analysis, the results obtained were generalizable to the paired data by the range of propensity scores . TherefoIn conclusion, we performed a propensity score-matched analysis using a large cohort of TMD patients with OFPHs and/or PHs. According to the results of our matched case–control study, SB, DC, and BP affected the stomatognathic system in terms of pain or fatigue while SB and DC did not affect TMD symptoms in patients without OPFHs and PHs. This implies that these habits might produce a risk for TMD symptoms owing to the coexistence of other habits.


A detailed chart-review of 157 consecutive claimants undergoing a 30-day HWDS trial (single pain management practice) from February 2018 to November 2019 compiled data on pain, restoration of function, quality of life (QoL), and polypharmacy reduction into a summary spreadsheet for an independent statistical analysis. Non-beneficial trials in 64 (40.8%) ended HWDS use, while 19 (12.1%) trial success charts lacked adequate data for assessing critical outcomes. Of the 74 final treatment study group charts, missing data points were removed for a statistical analysis. Pain chronicity was 7.8 years with 21.6 ± 12.2 months mean follow-up. Mean pain reduction was 35%, with 89% reporting functional improvement. Opioid consumption decreased in 48.8% of users and 41.5% completely stopped; polypharmacy decreased in 36.8% and 24.4% stopped. Zero adverse events were reported and those who still worked usually continued working. An overall positive experience occurred in 66.2% (p < 0.0001), while longer chronicity portended the risk of trial or treatment failure. Positive outcomes in reducing pain, opioid/polypharmacy, and anxiety/depression, while improving function/QoL, occurred in these challenging chronic pain injury claimants. Level of evidence: IIIPreviously promising short-term H-Wave Chronic pain, defined as pain that persists past normal healing times or for at least 3–6 months, has been estimated to eventually affect up to 20% of the world’s population . ChronicTypical chronic pain management often involves a combination of nonpharmacologic treatments such as physical therapy, cognitive behavioral therapy, and transcutaneous electrical nerve stimulation (TENS), added to pharmacologic agents including nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, topical anesthetics, opioids, and other controlled substances . Opioids® device stimulation (HWDS) is a unique type of transcutaneous electrotherapy that uses a specific proprietary waveform  to stimulate muscle fiber contractions, which are non-fatiguing and low-tension, mimicking natural voluntary motor contractions [® device utilizes a propriety waveform and parameters that are distinct from other available electrical stimulation devices such as TENS and NMES and should not be confused with the H waves associated with electromyography and the Hoffmann reflex. A recent critical review of the H-Wave® literature found significant benefits for a variety of musculoskeletal and neurological disorders, virtually without side effects, resulting in the lowering of pain medication use in 40–65% of neuropathic pain patients, while invariably improving functional status [H-Waveractions . This leractions ,14,15. Tl status .In addition to its clinical benefits, HWDS is relatively easy for patients to use, often being more cost-effective than polypharmacy and invasive procedures, with minimal to no side effects . While e® pre-clinical and clinical literature [® device delivers a current between 0 and 35 mA, a voltage between 0 and 35 V, a pulse duration up to 5 ms, and treatment components of 2 and 60 Hz [The detailed descriptions of stimulation intensities and paradigms can be found in a recent critical review of the H-Waveterature . Brieflynd 60 Hz .® trainer on how to properly apply and operate the device upon initiation of a 30-day trial period. Continuation and purchase of a home device only followed documented trial success, clearly noting improvements in function and perceived pain. Patients were typically followed every 3–6 months for approximately 2 years, completing several widely recognized and validated health questionnaires including the Visual Analog Scale (VAS), Brief Pain Inventory (BPI), Pain Disability Questionnaire (PDQ), Patient Health Depression Questionnaire (PHQ-9), and Generalized Anxiety Disorder (GAD-7) at various intervals during the defined study period. Patients that did not subsequently purchase an H-Wave® device, usually having failed a 30-day trial, or who did not consistently complete post-trial assessments, were excluded from the primary study group.This is a retrospective analysis of data from a consecutive cohort of legacy workers’ compensation claimants treated at the Jeffrey E. Hazelwood MD, PC clinic , who were prescribed HWDS  for refractory chronic pain reported between February 2018 to November 2019. The study time interval was selected to avoid potential issues related to COVID-19 and closure of a remote office. All participants had provided informed consent regarding their health outcomes and no protected health information was reported. This study was approved by the South Texas Orthopaedic Research Institute Institutional Review Board . General enrollment criteria for this dataset included being aged 18 or older, with well-established post-injury chronic pain having failed multiple prior treatments. All participants received in-clinic personalized instruction by a certified H-WavePre- and post-trial assessments were administered to patients who elected to continue using an HWDS device following successful trial. Patient demographics  and medical history  were documented. Preoperative use of pain medications, either opioid and/or a polypharmacy regimen, was reported. Symptom duration or date of injury (DOI) to trial and body part affected  were recorded. Patient-reported outcome measures were collected during clinic visits, including VAS, BPI, PDQ, PHQ-9, and GAD-7. Study patients were also directly surveyed by the device manufacturer with a pre-defined set of questions regarding their HWDS experiences, including functional status and pain measures. Data variables were independently compiled into a summary spreadsheet prior to subsequent independent statistical analysis. Based on a combination of collected subjective and objective data, overall patient outcomes were designated as poor, fair, good, or excellent.t-tests for categorical and continuous variables, respectively. Bivariate analysis assessed the association between survey responses. Stepwise linear regression analysis was performed to assess the correlation between outcome responses and DOI to trial time. In all testing, significance was established when p-value < 0.05 or the 95% confidence intervals (CI) for odds ratios excluded 1.0. All statistical analyses were conducted using SAS, version 9.4 .The primary outcomes were patient-reported experiences following prolonged HWDS device use. Survey responses were analyzed using contingency analysis for categorical variables, logistic regression analysis for dichotomized variables, ordinal regression analysis for Likert scale variables, and regression analysis for continuous responses. The means comparison tests were employed for pre–post contrasts, using chi-squared and ® device or failed to use it for at least 30 days. A review of 19 trial success patient charts revealed inadequate data for assessing clinical efficacy, with a documentation failure to report the critical outcome measures for pre–post assessments. With the exclusion of those patients (Excluded (n = 83)), the final study group consisted of a sample of 74 patients, who successfully completed a 30-day device trial and for which adequate data were collected , worker. Using a Visual Analog Scale (VAS) as one universally reported metric of subjective pain, there was a statistically significant average patient-reported reduction of −2.10 , representing an overall 35% improvement. Similarly, comparing pre- and post-treatment Brief Pain Inventory (BPI) scores, a statistically significant improvement (mean 28.2%) was observed (p < 0.0001). The study group patients using the Patient Health Depression Questionnaire (PHQ-9) also reported a 24.4% reduction in depression (p = 0.0096), as well as 31.0% reduction in anxiety (p = 0.0024) using the Generalized Anxiety Disorder (GAD-7) measures.Several QoL-related responses are recorded in Table 3p < 0.0001) that the study group patients (89%) were highly likely to experience mild or moderate functional improvement with H-Wave treatments, while 74.0% reported “moderate” or better benefits. The Pain Disability Questionnaire (PDQ) scores also reflected a 35% an overall improvement in disability/function (p < 0.0001).In terms of functional status , there wThe work- and medication-related data are recorded in p = 0.0038).The overall outcome/satisfaction results are recorded in n = 63, due to one outlier) with the study group, it was statistically significant that prolongation by a mean of 2.7 years of DOI to trial pain chronicity was more likely to portend trial failure . A logistic analysis of the combined trial failure and study group patients (n = 138) also indicated with statistical significance that longer chronicity was associated with poorer outcomes, defined as either trial failure or poor to fair treatment results .® device stimulation , lonHWDS treatment reduced subjective pain in 66/73 patients, with 82% of these reporting at least a “moderate” improvement, and a 35% relative VAS score reduction across the entire cohort. This is particularly promising, considering that these patients had already failed to improve with multiple conventional pain treatments. These results were surprisingly comparable to an older study where 78% of patients, with much less chronicity, experienced over 25% pain reduction ,20. WhilAn important relationship exists between chronic pain and polypharmacy usage, which was defined for the purposes of this study as the use of four or more medications to manage pain including, but not limited to, opioids and other controlled substances, NSAIDS, and acetaminophen . SeveralWhile this study demonstrated strong HWDS effects on keeping workers working, the fact that several non-working patients returned to work is remarkable. Workers’ compensation claimants have a reduced financial incentive to return to work, with data from the National Conference of State Legislatures indicating only a 4.9% chance of returning if over two years have passed since the initial absence . This clThis is the first HWDS study to highlight the importance of a standardized 30-day device trial before requesting preauthorization of purchase, something that is of keen interest to payers. Trial failure, without any accrued cost, occurred in 41% of these very chronic pain patients, a figure that would likely be somewhat lower for less chronically affected individuals. It should be noted that participants who failed to report pain and functional benefits during their trial continued to receive other treatments but were not subsequently studied regarding the clinical outcome measures, beyond some basic analyses of demographics, weight, and chronicity. Although there were individual exceptions, chronicity over about 10 years may be more likely to result in trial failure or poorer treatment outcomes. Approximately two-thirds of those who went on to purchase the device after a successful trial significantly benefited from HWDS. These odds of treatment success are quite good, especially considering the lack of other safe and cost-effective alternatives for such end-stage pain patients. Evidence-based medical treatment guidelines, particularly for workers’ compensation, have also suggested completion of an HWDS 30-day trial and prior failure of physical therapy and TENS . From a Despite promising findings and longer-term follow-up in this moderately sized cohort of consecutive chronic pain patients, this study was limited by its retrospective nature and having no comparative or control group. The final study group was significantly reduced in size through disqualification upon trial failure in 64 patients, but also due to inadequate data collection in 19 participants. Reporter bias and other confusion factors may also be an issue, since the collected data were documented by several assisting medical staff or self-reported by patients. Another minor study limitation includes limited applicability to the general population, particularly with skewed race and weight distributions. Future HWDS studies should include double-blinded, randomized control trials to assess improvements more effectively in pain, function, and opioid/polypharmacy use, also focusing on more normalized, non-claimant, and general populations, where better outcomes might be expected.® device stimulation has demonstrated efficacy in reducing chronic pain and improving function and quality of life, even in a difficult to treat cohort of workers’ compensation claimants with symptom duration averaging almost 8 years. With longer-term follow-up than previous studies reporting clinically significant outcomes, HWDS safely and cost-effectively brought relief to two-thirds of the refractory chronic pain patients completing a successful 30-day device trial, resulting in significant improvement in pain and functional status measures, as well as reduction or cessation (48.8%/41.5%) of opioid use. While mean reduction in self-reported pain decreased by 35%, with similar anxiety and depression benefits, 89% of the study cohort experienced functional improvements. HWDS should be considered a viable non-opioid treatment option for refractory chronic pain patients.H-Wave


Epidermoid cysts (ECs) are one of the most common causes of secondary trigeminal neuralgia (TGN). However, most previous studies have primarily focused on whether complete tumor resection was achieved, and few studies have discussed the primary goal of pain relief.The present study provides intraoperative strategies for trigeminal nerve (TN) management in patients with TGN secondary to an EC and observed long-term follow-up outcomes.A total of 69 patients with TGN secondary to an EC at our hospitals were included (January 2011–June 2021). The same surgical team performed all surgeries using a retrosigmoid approach. After EC removal, different methods for TN management were used, including microvascular decompression (MVD), sharp capsulectomy, nerve combing and embedded cholesterol crystal excision. The epidemiological, clinical, and surgical data were extracted.The total EC removal rate was 92.8% (64/69). All patients achieved initial pain relief postoperatively, and 12 patients (17.4%) experienced varying degrees of hemifacial hypesthesia, which was relieved within 3–6 months. Three patients (4.3%) reported partial pain recurrence within a median follow-up period of 5.5 (0.5–10.5) years, which was relieved completely after low-dose carbamazepine administration.The primary goal of surgical tumor removal for patients with TGN secondary to an EC is relief of the main symptom of tormenting pain. The selection of an appropriate strategy for TN, including MVD, sharp capsulectomy, nerve combing or embedded cholesterol crystal excision, should depend on the patient's situation. The incidence of intracranial epidermal cysts (ECs), also named intracranial cholesteatomas, accounts for approximately 1% of all intracranial tumors , and theγ-knife surgery) before admission to our hospitals, and nine of these patients had obvious postblock hypesthesia. The ethics committee of the two hospitals involved approved this study. The patient data were anonymous, and informed consent was not necessary.All patients who underwent surgery for TGN at our hospitals from January 1, 2011, to June 30, 2021, were reviewed retrospectively. The diagnosis of TGN was made in 2,048 cases according to the criteria for classic TGN 13.1.1) of the International Classification of Headache Disorders 3 (ICHD-3). As part of the routine clinical management of TGN, all patients underwent a preoperative three-dimensional time-of-flight (3D-TOF) magnetic resonance imaging (MRI) examination. In cases of prepontine cistern enlargement or abnormal signals, contrast enhancement or 3D fast imaging using steady-state acquisition (3D-FIESTA) was applied  (13). Of.1.1 of tvia sharp dissection. After clear and complete tumor removal, primary attention was focused on the management of the TN root. Different surgical procedures for TN management were performed according to the type classification, as discussed below.All patients underwent treatment with a standard suboccipital retrosigmoid approach. After the release of cerebrospinal fluid (CSF) under a microscope and retraction of the cerebellar hemisphere, a pearl-like space-occupying lesion with an intact capsule was observed at the CPA. The TN, facial-acoustic nerve, and lower CNs were compressed and encapsulated. After opening the arachnoid membrane, intracapsular resection was performed as the primary procedure, including clearing of the cholesteatomatous tumor tissue in all corners using an aspirator and dissector and the tumor tissue on the tentorium cerebellum and in the contralateral prepontine cistern by adjusting the angle of the microscope. For tumor capsules attached to the brain stem, compulsory resection was not performed to avoid damaging the penetrating vessel, which results in severe consequences. In cases where the tumor wrapped the facial-acoustic, abduction and trochlear nerves, a small aspirator tube with a well-controlled suction force was used because these nerves are thin and delicate, and excessive suction could cause direct damage. The adhered tumor capsule was cut and removed via sharp dissection using microscopic scissors  was found, and microvascular decompression (MVD) was performed . The remFollow-up evaluations were performed 6 and 12 months post-operatively and then annually thereafter and included routine physical examination, MRI and facial sensory testing in most cases. Telephone interviews were performed if the patients failed to visit our clinic at the scheduled time. In addition to other CN complications, we primarily evaluated the initial pain relief, pain recurrence, and any type of sensory disturbance using the Barrow Neurological Institute (BNI) pain intensity score and the facial numbness score . CompletSixty-nine of the 2,048 cases were included in the study. The mean age of the 69 EC patients was 49.8 (17–77) years. Most patients were women . The mean disease duration was 61.5 (1–480) months, and the mean follow-up duration was 5.5 (0.5–10.5) years. The affected areas and other clinical characteristics are shown in All patients had sutures removed and were discharged 5–7 days post-operatively. Immediate and complete pain relief (BNI pain score I) was achieved in all 69 cases. Postoperative MRI demonstrated total resection in 64 cases and subtotal resection in the other five cases because the tumors on the supratentorial and contralateral CPA parts were relatively large. The main complication was unilateral facial hypesthesia, which occurred as a new symptom or exacerbation of the original bradyesthesia in 12 cases, including three of the 11 type Ib EC patients who underwent combing. This bradyesthesia was relieved 3–6 months post-operatively in all patients. Other presenting complications included acute subdural hematoma in three cases (detected on routine CT checkup 24 h post-operatively), which presented as a thin-layer hematoma with no clinical symptoms and were absorbed spontaneously within one month in all cases, aseptic meningitis in eight cases, diplopia in seven cases, including trochlear nerve injury in four cases and abducens nerve injury in three cases, and hearing loss in five cases. During the follow-up period of 0.5–10.5 years, no significant enlargement of the tumor was observed in the five patients in whom subtotal resection was achieved. Three patients (4.35%) reported partial pain recurrence (BNI pain score II–III) two and three years post-operatively. Treatment for recurrence in these patients included the use of low-dose carbamazepine (<200 mg/d), which provided a satisfactory analgesic effect. Pain-free survival was defined as the time to recurrence of facial pain after surgery. Kaplan–Meier curves were constructed based on pain-free survival . The difThe occurrence of ECs in the CPA is rare, but we have treated numerous cases at our TGN center because the most common onset symptom is TGN. The 69 patients with TGN secondary to an EC included in our series were primarily characterized by a young mean age, pain in the V2 and V3 regions, and a similar onset of symptoms and typical vascular compression presenting as simple TGN . The totThe key for the successful treatment of TGN secondary to an EC is pain relief. The immediate pain relief rate was 100% in our study, and long-term follow-up observation only revealed partial pain recurrence in three cases (4.3%). The incidence of nerve-related complications was also low. Hemifacial hypesthesia was the main symptom, but its postoperative clinical presentation was mild and caused an insignificant impact on patients' daily activities. The symptoms were relieved in 3–6 months in most patients.A few studies have reported research on TGN secondary to an EC. Kabata 2002) analyzed 28 cases and emphasized that straightening the neuraxis by cutting and removing the adherent tumor capsule and arachnoid membrane was mandatory for the relief of pain and prevention of pain recurrence. With a mean follow-up period of 11.5 years, they detected pain recurrence symptoms in three patients (10.7%). However, their postoperative TN injury rate was as high as 64.3% (18/28). Together with other CN (III-V) injuries, the overall incidence accounted for approximately two-thirds of all patients. Therefore, an excellent outcome was achieved in only 57.1% (16/28) 02 analyz. Other sThe pathogenesis of TGN secondary to an EC is likely related to the following three conditions: (1) nerve compression from vascular compression; (2) direct compression of the nerve by the tumor; and (3) irritation of the chemicals within the EC or aseptic inflammation of the TN. These factors may work independently or synergistically on the TN to cause demyelination of the nerve and formation of pseudosynaptic connections, which ultimately result in abnormal TN tactile conduction , 24.The principle of our surgical strategy for TN management is removal of the above factors.1.Strategy for TGN management. Some researchers have advocated conservative management strategies for ECs involving the CN . We part2.OVs may cause TGN in EC patients. The only controversy is that some researchers believe that the OV is the only cause . We founThe present study has some limitations. First, it was only a retrospective study. Second, TN combing is an innovative method that has not been generally accepted. Therefore, more studies are required to provide verification of its efficacy and long-term outcomes.The primary goal of EC removal as a treatment is relief of the tormenting pain. Caution should be taken to avoid oversight of any possible OVs for decompression. The selection of an appropriate strategy for TGN, including sharp capsulectomy, nerve combing or embedded cholesterol crystal excision, should depend on the extent of tumor invasion into the TN.


Headache recurrence is a common feature of acute therapies, whether approved or still in development, and continues to be a significant problem for both the patient and the clinician. Further complicating this issue is lack of standardization in definitions of recurrence used in clinical trials, as well as disparity in patient characteristics, rendering a comparison of different acute medications challenging. Recurrence has serious clinical implications, which can include an increased risk for new-onset chronic migraine and/or development of medication overuse headache. The aim of this review is to illustrate variability of recurrence rates depending on prevailing definitions in the literature for widely used acute treatments for migraine and to emphasize sustained response as a clinically relevant endpoint for measuring prolonged efficacy.A literature search of PubMed for articles of approved acute therapies for migraine that reported recurrence rates was performed. Study drugs of interest included select triptans, gepants, lasmiditan, and dihydroergotamine mesylate. An unpublished post hoc analysis of an investigational dihydroergotamine mesylate product that evaluated recurrence rates using several different definitions of recurrence common in the literature is also included. Depending on the criteria established by the clinical trial and the definition of recurrence used, rates of recurrence vary considerably across different acute therapies for migraine, making it difficult to compare results of different trials to assess the sustained  and the prolonged  efficacy of a particular study medication.A standardized definition of recurrence is necessary to help physicians evaluate recurrence rates of different abortive agents for migraine. Sustained pain relief or freedom may be more comprehensive efficacy outcome measures than recurrence. Future efficacy studies should be encouraged to use the recommended definition of sustained pain freedom set by the International Headache Society. Treatment efficacy in migraine clinical trials can be assessed using a range of possible outcome measures, from symptomatic relief at specific time points post-treatment to persistence of treatment response . The IntComplete relief of head pain and no recurrence are important attributes of acute therapy for migraine identified from surveys of individuals with migraine , 5. LackDespite advances in migraine care, recurrence of migraine remains a major problem for patients and providers alike, which requires careful consideration when evaluating treatment efficacy in clinical trials , 13. SevA literature search of PubMed for clinical trials of approved acute therapies for migraine that reported recurrence rates was performed. No restriction was placed on the publication year. Study drugs of interest included ubrogepant, rimegepant, lasmiditan, INP104, and triptans. For the purpose of this review, in order to simplify issues with medication evaluation, we did not include noninvasive neuromodulation devices used to acutely treat migraine. Studies of primary focus were manually identified and were included if they were clinical trials , provided any definition of recurrence, and reported recurrence rates.The focus of this review was on pain rather than on the other, often debilitating, symptoms of migraine. For the agent rimegepant, only studies that evaluated the orally disintegrating tablets (ODTs) were included, because this formulation has been approved by the US Food and Drug Administration (FDA) . The litThe recognition of recurrence as a clinical concern, which did not arise until 1989, was generated by the introduction of sumatriptan as an abortive therapy for patients with migraine . RecurreIn 1995, Pini and colleagues conducted a double-blind, randomized, placebo-controlled, parallel-group, multicenter study that evaluated the incidence of recurrence in 238 patients with migraine following administration of a 100 mg dose of oral sumatriptan succinate for a single attack. Patients were instructed to take sumatriptan or placebo at the earliest sign of a migraine. Rescue medication, except for ergotamine tartrate, was permitted after 4 h post-dose.Recurrence was defined as the reemergence of moderate or severe headache within 24 h of dosing after initial headache relief (mild or none) 4 h after treatment. With sumatriptan, 65% 92 of 142) of patients experienced headache relief at 4 h post-dose, compared with 40% (32 of 80) of those treated with placebo. In the sumatriptan group, 17.4% (16 of 92) of patients experienced recurrence from 4 to 24 h after the initial dose, compared with 12.5% (4 of 32) of those in the placebo group; these differences were not statistically significant  at 4 h, again using the 4-h effectiveness time for initial relief. Over three attacks, 77% to 83% of patients in the sumatriptan 100 mg group, 76% to 81% in the sumatriptan 50 mg group, 65% to 70% in the sumatriptan 25 mg group, and 33% to 39% in the placebo group experienced headache relief by 4 h post-dose, with 28% to 30% of patients in the sumatriptan 100 mg group, 29% to 34% in the sumatriptan 50 mg group, 26% to 39% in the sumatriptan 25 mg group, and 35% to 48% in the placebo group experiencing recurrence from 4 to 24 h post-dose  becoming mild or absent (grade 1/0) in all three studies. Headache recurrence at 24 h was defined as “grade 3 or 2 headache improving to grade 1 or 0, but subsequently returning to grade 2 or 3 within 24 h” of the first dose in patients who responded at 4 h. Response at 2 and 4 h ranged from 37 to 46% and 56% to 65% with frovatriptan, compared with 21% to 27% and 31% to 38% with placebo, respectively, in all three studies. The percentage of patients who were pain free at 2 and 4 h ranged from 9 to 14% and 27% to 32% with frovatriptan, compared with 2% to 3% and 9% to 14% with placebo, respectively, in all three studies. Overall, 47% to 51% of patients in the frovatriptan group, compared with 22% to 27% of those in the placebo group, reported a sustained response . The rate of recurrence within 24 h of the first dose ranged from 10 to 25% with frovatriptan, compared with 24% to 31% with placebo in all three studies , single-dose efficacy becomes important. Recurrence may be prevented or reduced with the use of an agent with a long plasma elimination half-life or slow receptor dissociation , 36. A lcurrence , 26, 37.currence . Recurrecurrence .DHE has been used and recommended for the treatment of migraine since 1946 . DHE int(A)recurrence in patients who experienced pain relief at 2 h(B)recurrence or use of rescue medication in patients who experienced pain relief at 2 h(C)recurrence in the modified intent-to-treat (mITT) population, and(D)recurrence or use of rescue medication in mITT patientsAs mentioned earlier, MAP0004 was an orally inhaled formulation of DHE mesylate, but it did not receive FDA approval , 20. In The mITT population was defined as patients who treated a qualifying migraine and for whom ≥ 1 post-treatment assessments were available. The assessments were the usual primary and secondary outcome measures, including 2-h pain status, recurrence, rescue medications, and 24-h pain status. Sustained pain relief  from 2 to 24 h was reported among 44% (167 of 382) of patients treated with MAP0004, compared with 20% (76 of 387) of those treated with placebo . FurtherWhen the most commonly used definition in clinical trials (Definition A) was applied, recurrence was reported in 6.5% 15 of 231) of patients treated with MAP0004 and 14.7% (20 of 136) of those treated with placebo over 2 to 24 h after the initial dose. Recurrence varied, however, when Definitions B and C were used. Recurrence was reported in 21.6% (50 of 231) of MAP0004-treated patients vs 39.0% (53 of 136) of placebo-treated patients when Definition B was used, whereas recurrence was reported in 3.8% (15 of 397) of patients treated with MAP0004 compared with 5.0% (20 of 397) of those treated with placebo when Definition C was used. When Definition D was applied, recurrence was reported in 12.6% (50 of 397) of patients treated with MAP0004 vs 13.4% (53 of 397) of those treated with placebo. The same trend was observed when recurrence was recorded from 2 to 48 h after the initial dose. When Definition A was used, recurrence occurred in 10.4% (24 of 231) of patients treated with MAP0004 and 17.6% (24 of 136) of those who received placebo. Recurrence was reported in 29.4% (68 of 231) of MAP0004-treated patients vs 41.2% (56 of 136) of placebo-treated patients when Definition B was applied. With Definition C, recurrence was 6.0% (24 of 397) in the MAP0004 group and 6.0% (24 of 397) in the placebo group. When Definition D was used, recurrence was reported in 17.1% (68 of 397) of patients treated with MAP0004 compared with 14.1% (56 of 397) of those who received placebo  is consistent with the most common criteria defining recurrence in the literature, in which use of rescue medication is not taken into consideration when calculating recurrence rates. For example, in the original presentation of the FREEDOM-301 study outcomes, Definition A was used, with recurrence at 24 h reported in 6.5% of patients administered MAP0004 compared with 14.7% of patients administered placebo. This definition, however, may provide a false impression, as sustained pain relief from 2 to 24 h  was achieved by 44% of patients treated with MAP0004 vs 20% of those who received placebo , 19. DefGepants are a class of small molecules that act as antagonists to the calcitonin gene-related peptide receptor –33, 50. In 2019, Croop and colleagues published results from a randomized, double-blind, placebo-controlled, Phase 3 study that assessed the safety, efficacy, and tolerability of a 75 mg dose of an ODT formulation of rimegepant in 1,351 patients who received treatment for a single migraine attack of moderate or severe intensity. Pain recurrence was defined as the “percentage of participants who were pain-free at 2 h[ours] but then later had some amount of pain” within 48 h of drug administration; rescue medications were permitted 2 h post-dose. Sustained pain freedom was defined as achieving pain freedom from 2 h to 24 or 48 h. Rescue medications included aspirin, ibuprofen, and acetaminophen , as well as naproxen , antiemetics, or baclofen. Note that no second dose of rimegepant was allowed. Two hours after administration of the single dose of rimegepant ODT 75 mg, 21.2% (142 of 669) of patients reported pain freedom, compared with 10.9% (74 of 682) of those who received placebo. Sustained pain freedom from 2 to 48 h post-dose was reported in 13.5% (90 of 669) of patients in the rimegepant group, compared with 5.4% (37 of 682) of those in the placebo group. Additionally, 36.6% (52 of 142) of patients in the rimegepant group experienced recurrence from 2 to 48 h after the initial dose, compared with 50.0% (37 of 74) of patients in the placebo group  of patients in the 50 mg group and 21.2% (95 of 448) of those in the 100 mg group reported pain freedom at 2 h after the initial dose, compared with 11.8% (54 of 456) of those in the placebo group. Further, in the ubrogepant groups, 12.7% (53 of 418) of patients in the 50 mg arm and 15.4% (68 of 441) of those in the 100 mg arm reported sustained freedom from pain , compared with 8.6% (39 of 452) of those in the placebo group. In the pooled 50 mg and 100 mg ubrogepant groups, 38.6% (336 of 871) of patients took an optional second dose, with 20.0% receiving ubrogepant. Of patients who received ubrogepant 50 mg or ubrogepant 100 mg, 16.3% (69 of 423) of patients and 15.2% (68 of 448) of patients, respectively, used rescue medication for either a nonresponding or a recurrent migraine headache 2 to 48 h following an initial dose, compared with 28.7% (131 of 456) of those in the placebo group. It is unclear from the published data whether a second dose was taken because of an early recurrence or a lack of efficacy from a single dose  of patients in the 25 mg arm and 21.8% (101 of 464) of those in the 50 mg arm reported pain freedom at 2 h after the initial dose, compared with 14.3% (65 of 456) of patients in the placebo group. Sustained pain freedom was defined as pain freedom without the need for a second dose or rescue medication and with no occurrence thereafter of a moderate or severe headache 2 to 24 h after taking the initial dose. In the ubrogepant treatment arms, 12.7% (55 of 432) of patients in the 25 mg group and 14.4% (66 of 457) of those in the 50 mg group reported sustained pain freedom 2 to 24 h after the initial dose, compared with 8.2% (37 of 451) of patients in the placebo group. In the pooled 25 mg and 50 mg ubrogepant groups, 37.6% (338 of 899) of patients received an optional second dose of the study medication, compared with 42.8% (195 of 456) of those in the placebo group. Additionally, 20.5% of patients in the ubrogepant 25 mg group, 16.4% of patients in the ubrogepant 50 mg group, and 25.7% of those in the placebo group used rescue medication 2 to 24 h after the initial dose for either a nonresponding or a recurrent migraine headache  is the only FDA-approved ditan for the acute treatment of migraine  but then experienced recurrence of mild, moderate, or severe migraine pain and took a second dose of study drug up to 24 h[ours] from the first dose.” The proportions of patients who reported pain freedom in the ITT population  at 2 h were 28% (169 of 598) in the lasmiditan 50 mg group, 30%  in the lasmiditan 100 mg group, and 35% (396 of 1120) in the lasmiditan 200 mg group, compared with 18%  in the placebo group. The proportions of patients who took a second dose for recurrence were 8% (13 of 169) in the lasmiditan 50 mg group, 10% (35 of 337) in the lasmiditan 100 mg group, and 7% (28 of 396) in the lasmiditan 200 mg group, compared with 10% (21 of 206) in the placebo group. The study also calculated the recurrence rate based on the definition used in earlier triptan studies. The recurrence population was defined as patients who achieved none or mild pain at 2 h, that is, 2-h pain relief after the first dose, and subsequently reported moderate or severe pain . Recurren = 16,777), 17.1% of all treated migraine attacks that achieved pain freedom at 2 h had recurrence of pain up to 48 h post-dose . Similarly, the mITT population was defined at the treated migraine attack level . Pain freedom and relief analyses excluded treated migraine attacks with no pain severity rating at baseline or with a severity rating of ‘‘none’’. The proportions of migraine attacks with 2-h pain freedom in the ITT population were 26.9%  in the lasmiditan 100 mg group and 32.4% (2665 of 8232) in the lasmiditan 200 mg group, with 29.6%  for all treated migraine attacks. The percentages of migraine attacks treated with medications other than lasmiditan before and after the 2-h assessment were 3.3% and 8.2%, respectively. In the ITT population, 6.1% 302 of 4963) of all treated migraine attacks that achieved pain freedom at 2 h were treated with a second dose of lasmiditan, whereas in the mITT population  that delivers a nasal formulation of DHE mesylate using the Precision Olfactory Delivery (POD®) technology  was FDA-approved in September 2021 (TRUDHESA®). Smith and colleagues reported results from the STOP 301 trial, which was a pivotal, interventional, open-label, Phase 3 study to assess the safety, tolerability, and exploratory efficacy of DHE mesylate administered with the POD technology to the upper nasal space over 24 or 52 weeks. A total of 354 patients comprised the full safety set . This set treated their migraine attacks with INP104 for up to 24 weeks, with a subset of 73 patients treating their migraine attacks for 52 weeks. Comparisons were made with data collected during the initial 4-week screening period, when patients were receiving their best usual care. For the first treated migraine, 38.0% (126 of 332) of patients self-reported pain freedom at 2 h with INP104, whereas 30.1% (92 of 306) of patients self-reported pain freedom at 2 h for their last migraine at baseline treated with best usual care. Recurrence was defined as the onset of a new headache prior to 24 or 48 h post-dose in patients who were pain free at 2 h post-dose. Recurrence at 24 h and 48 h post-dose was self-reported in 7.1% (9 of 126) of patients and 14.3% (18 of 126) of patients, respectively, who treated their first migraine attack with INP104  can contribute to this misrepresentation. In general, understanding recurrence in migraine requires evaluation of the definition of recurrence. Defining recurrence to include both the return of pain and utilization of rescue medication but limiting the definition to the population of patients who experience initial pain freedom may provide a more complete description of meaningful persistence of migraine relief. A standardized definition is required to help physicians compare the rates of recurrence among different acute treatments for migraine, which may ultimately lead to improved quality of life among patients with migraine. The sustained pain-free definition set by the IHS is a better outcome measure of prolonged efficacy than recurrence rate for acute medication trials.


Herpes zoster (HZ)-associated pain can lead to severe pain and reduced quality of life. Exploring effective treatment and the risk factors of zoster-associated pain has become important.Interventions including nerve block, radiofrequency, and thermocoagulation were used for zoster-associated pain. The data of 131 patients with HZ and 230 patients with postherpetic neuralgia (PHN) were collected at baseline, 2 weeks, 3, 6, and 12 months after the intervention. Visual analog scale (VAS) and Brief Pain Inventory (BPI) scores at different time points were analyzed by two-way repeated measures ANOVA with Group as the between-subject variable (different pain durations and areas), Time as the within-subject variable , and Group × Time as the two-way interaction. Besides, the effective rate, adverse effects, and medication were also recorded. The risk factors of PHN were analyzed by logistic regression.A total of 25 (19.08%) patients with HZ continued to have pain in the initially affected area after 3 months. The VAS scores and the BPI quality of life scores of patients with HZ-associated pain were significantly reduced from baseline to 2 weeks, 3, 6, and 12 months after the interventions. There was no significant difference in VAS and BPI scores in different pain areas and pain durations. No significant Group × Time interaction was observed. Age, diabetes mellitus, and immune-related diseases were risk factors of PHN.Interventions could significantly improve the pain degree and life quality of patients with zoster-associated pain, and the positive effect of intervention did not change with pain duration and area. Advanced age, diabetes, and immune-related diseases are risk factors of PHN. Herpes zoster (HZ) is caused by varicella herpes virus infection with an annual incidence of 2–5 per 1,000, which might lead to severe pain . Once PHAt present, treatment for zoster-associated pain includes medication and interventional treatment. Medication includes gabapentin, pregabalin, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, and topical treatment. Interventional treatment includes epidural or paravertebral nerve blocks, pulsed radiofrequency (PRF), and thermocoagulation. Nerve block is recommended, while oral medication is ineffective, but evidence of PRF and thermocoagulation for first-line treatment is limited. Furthermore, the risk of PHN may be related to some clinical features of HZ, including prodromal pain, degree of pain, and rash density . The incChiCTR.org.cn  and was approved by the Ethics Committee of West China Hospital, Sichuan University, Chengdu, China . The data of patients diagnosed with HZ and PHN were extracted from the department of pain management of West China Hospital of Sichuan University from September 2017 to September 2018. In this study, HZ included the acute stage (1 month after rash onset) and the subacute stage after the acute phase and before PHN was diagnosed (1–3 months), while PHN was diagnosed as pain that persists for more than 3 months after rash onset. An experienced pain physician evaluated neuropathic pain according to the NeuPSIG grading system and assessed the pain intensity by the visual analog scale (VAS) (This retrospective study was registered at le (VAS) . InclusiA database was set up for this study in the clinical research data management system of West China Hospital. The researchers could independently design the clinical case report form (CRF) and filter the information, including the general information, course of the disease, location of pain, clinical intervention, pain degree, quality of life, and other information. Besides, the database provides the features of automatic enrollment, follow-up reminders, authority allocation, and other functions. The researchers collected relevant data as follows:(1) Clinical data of patients, including demographic data, disease-related data, and medical history.(2) Pain was measured by VAS and pain relief rate. VAS is a 10-cm straight line that only marks the pain at both ends. One end is 0, indicating no pain; the other end is 10, indicating severe pain. Patients are asked to mark the level of pain on the line. The pain relief rate is ranked as apparent effect (pain relief ≥50% after treatment), effective (pain relief 30–50%), and ineffective (pain relief <30%). The remission rate was calculated .(3) Quality of life was measured by the Brief Pain Inventory (BPI) quality of life part, which contains 7 dimensions, including general activity, mood, walking ability, normal work, relation with other people, sleep, and enjoyment of life. Each dimension was measured by scores that ranged from 0 to 10, with higher scores indicating a greater impact on the quality of life.(4) Adverse reactions include dizziness, nausea, vomiting, puncture injury , infection, limb movement disorder, incontinence, and respiratory disease.(5) Medication: The types and doses of drugs.(6) Follow-up time: baseline, 2 weeks, 3, 6, and 12 months after the intervention.Patients with HZ usually received different nerve block methods . Patients in the subacute stage (1–3 months) received CT-guided PRF nerve regulation twice with an interval of 1 week. Two or three intervertebral foramina of adjacent segments were located and punctured with a radiofrequency catheter under the guidance of CT. After reconfirming the target by sensory-motor electrical stimulation, the PRF mode was administered at 42°C for 15 min, and then 1 ml of the mixture of compound betamethasone and lidocaine was injected for its anti-inflammation and analgesic effect.For patients with PHN in the trigeminal nerve distribution region, physicians usually punctured the radiofrequency needle focusing on the foramina of the lesion side under CT guidance. After reaching the foramina, a mixture of 40 mg methylprednisolone and 1 ml of 0.5% ropivacaine was injected into the trigeminal ganglion. If there was no adverse reaction in 5 min, 0.5 ml of 0.5% adriamycin was injected. When PHN occurred in the area of the trunk, CT-guided radiofrequency thermocoagulation and analgesia injection were administered. After locating two or three intervertebral foramina of adjacent segments, the physician punctured the radiofrequency catheter under the guidance of CT and reconfirmed the target by sensory-motor electrical stimulation. Then, standard radiofrequency model has two cycles at 80°C, 2 min per cycle was performed, and after that, 1 ml of the mixture of compound betamethasone and lidocaine was injected into the intervertebral foramen and ipsilateral epidural cavity under CT guidance. If no adverse reactions were observed in 5 min, the physician could inject 1 ml of 0.33% or 0.5% adriamycin at each segment injection. In the area of limbs, radiofrequency was changed from standard radiofrequency to PRF to avoid long-time continuous radiofrequency affecting the motor neurons associated with limb movement, which might influence the quality of life. Besides, 2–3 ml of analgesic fluid was injected in each segment instead of adriamycin.The SPSS version 23.0 software was used for statistical analysis. Descriptive statistics were used to summarize the baseline characteristics of the participants. The measurement data were expressed as mean ± standard deviation, and the ranked data were represented as rate and ratio. VAS and BPI scores in patients with HZ and PHN at different time points were analyzed by two-way repeated measures ANOVA with Group as the between-subject variable (different pain durations and areas), Time as the within-subject variable , and Group × Time as the two-way interaction. Linear regression was used to analyze the correlation between age, gender, course, location, complications, and VAS score. Logistic regression analysis was performed in patients with HZ to explore the risk factors of PHN. The dependent variable was whether patients with HZ developed PHN. The independent variables included age (<65 years or ≥65 years), diabetes, immune-related disease, and osteoporosis. These binary variables were assigned “yes” to 1 and “no” to 0 in logistic regression analysis. P < 0.05 was considered statistically significant.The data of 131 patients with HZ and 230 patients with PHN were extracted from the database system from September 2017 to September 2018, with an overall sample loss rate of 6.36%. The basic characteristics of patients are shown in P < 0.001). There was no significant difference in VAS in different pain areas  and pain durations (P = 0.555 in PHN). No significant Group × Time interaction was observed, which indicated that different groups followed similar trends of VAS over time and the intervention had a positive effect on patients with different pain durations and areas.A total of 25 (19.08%) patients with HZ continued to have pain in the initially affected area after 3 months. In P < 0.05)  .P < 0.001). There was no significant difference in BPI in different pain areas  and pain durations (P = 0.117 in PHN). There was no significant Group × Time interaction, suggesting that different groups followed similar trends of BPI over time, and the positive effect of intervention did not change with pain duration and area  cases of adverse reaction were reported after intervention in patients with PHN, including 10 cases of dizziness and nausea, 3 cases of palpitation, 4 cases of transient pain after the invasive treatment, and 1 case of urinary disturbance which was relieved after catheterization.N = 131) and PHN (n = 230) was positively correlated with age . Notably, 19.08% of patients with HZ developed PHN after the intervention (25/131). Logistic regression analysis found that the risk factors of PHN were advanced age , diabetes , and immune-related diseases . Osteoporosis was not the risk factor of PHN .Linear regression analysis showed that VAS score in patients with HZ  to mild pain (VAS ≤ 3) after interventions, which was similar to a previous study . PatientP > 0.05). With the relief of pain, the total scores of BPI decreased after the intervention, and 7 dimensions including general activity, mood, walking ability, normal work, relation with other people, sleep, and enjoyment of life were improved.After active clinical interventions, 25 (19.08%) patients developed PHN, which was less than a previous report . We alsoIn some pain areas and durations such as trunk, hip, and 7–12 months group, postoperative VAS scores and BPI quality of life scores decreased 2 weeks after the intervention, with a recurrent increase or stabilization in 3 months, and then gradually improved from 6 to 12 months, which might be related to the mechanism of radiofrequency thermocoagulation, adriamycin, and glucocorticoid injection. Radiofrequency relieved the pain by destroying nerve fibers, especially unmyelinated nerve fibers . AdriamyIn addition, the decline in the BPI score was greater than the VAS score, which suggested that the improvement in quality of life is superior to the relief of pain. Long-term chronic pain, especially neuropathic pain, is prone to cognitive behavioral disorders such as anxiety and depression. At present, a large number of studies have shown that emotional state has a great impact on chronic pain. Therefore, psychological and behavioral interventions can help patients to accept the impact of pain and establish self-management awareness of chronic pain . At the Adriamycin is used to treat PHN because of its destructive effect on the nerve by reversing axonal transport. As basic studies have confirmed that a high concentration of adriamycin may damage motor neurons  and exceWe found that the degree of pain and the quality of life are less affected in the facial area of patients with PHN, which may be due to the relatively small range of skin lesions in this area and avoiding pain triggers easily.Considering the repair process of neuropathic injury, PHN was suggested to be classified according to the duration of the disease including stage 1 (3 months), stage 2 (3–6 months), and stage 3 (>6 months), which might be useful for stratified analysis . In thisIn a large retrospective study containing 119,413 patients with HZ, the risk factors of PHN included age, women, immune-related diseases, asthma, diabetes, smoking, underweight, and obesity . In lineHowever, there are some limitations in this study due to the retrospective characteristics of the analysis. First of all, the missing placebo arm might weaken the credibility of the results. Besides, the individual dosage of analgesic medication may have a greater impact on therapeutic effect than the interventions. There are some missing values of the individual dosage of analgesic medication; as a result, we only analyzed the proportion not the dosage of analgesic medication, which could be analyzed in the future study by improving the database system. Furthermore, the comparison between the interventions might not be thorough enough, which could be improved in further study.Interventions could significantly improve the pain degree and life quality of patients with zoster-associated pain, and the positive effect of intervention did not change with pain duration and area. Besides, advanced age, diabetes, and immune-related diseases are risk factors that could influence the occurrence of PHN.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study was approved by the Ethics Committee of West China Hospital, Sichuan University, Chengdu, China . Written informed consent from the patients/participants or patients/participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.LC and JL were the major contributors to writing the manuscript. JL designed the study and collected the data with LC. PY and LY analyzed the data. HL and YZ revised the manuscript. All authors read and approved the final manuscript.This study was supported by grant 2022NSFSC0710 from the Science and Technology Department of Sichuan Province and grant 2022-YF05-01343-SN from the Chengdu Science and Technology Bureau. The funders did not participate in any aspect of the trial, including design, data collection, analysis, or interpretation.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.