BackgroundMastalgia often impairs the physical, social, and sexual lives of women. It may manifest in both cyclical or acyclical patterns. The psychoneurotic association of mastalgia has been claimed for a long time in various available literature. Several treatment options have been used and are available in the market for mastalgia, but no specific guidelines are currently in place at the global or local levels. This study aims to evaluate the psychological status and effectiveness of various treatment options in women presenting with mastalgia.MethodsThis study was conducted in the General Surgery outpatient department from February 1 to November 30, 2021, at King George’s Medical University, Lucknow, India. Females of all age groups presenting to the General Surgery outpatient department with unilateral/bilateral breast pain and/or chest wall pain were considered for this study. Pregnant patients, those with a history of allergy to drugs, or those who were lost to follow-up were excluded from the study. The psychological status of patients was assessed using the Depression Anxiety and Stress Scale (DASS-42) scale. Pain assessment was performed using a visual analog scale (VAS). Patients were divided into five categories: (i) isolated chest wall pain, (ii) isolated breast pain, (iii) both chest wall and breast pain, (iv) pain with an associated lump(s), and (v) pain and tenderness isolated over the lump, and two groups: Group-A: VAS≤4, and Group-B: VAS>4. Group B patients in Category iv were randomized into two groups: topical non-steroidal anti-inflammatory drugs (NSAIDs) or evening primrose oil+vitamin E. The next line of treatment was tamoxifen 10mg followed by danazol 100mg followed by ormeloxifene 30mg.ResultsThe mean age of 106 participants enrolled was 31.59±10.52 years. The mean scores, using the DASS-42 scale, for depression, anxiety, and stress were 7.31±8.53, 7.08±6.57, and 11.15±8.07, respectively. The depression, anxiety, and stress scores had no significant correlation with pain scores , or duration . Twenty-nine of 43 patients (67.44%) responded to topical NSAIDs as first-line treatment, and out of the remaining, 6.98% responded to evening primrose oil + vitamin E, 18.60% to tamoxifen, and 4.65% to danazol. Twenty-nine of 32 patients (90.63%) responded to evening primrose oil+vitamin E as first-line treatment, while 6.25% and 3.12% responded to tamoxifen and danazol, respectively. ConclusionsBoth topical NSAIDs and evening primrose oil + vitamin E were found effective first-line treatment options in the majority of patients. Hence, it is always advisable to start such patients on topical NSAIDs, or evening primrose oil + vitamin E, before switching over (if no resolution of pain is reported with these drugs) to higher and more severe treatment options. The duration or severity of pain did not correlate with the psychological condition of the patient. Mastalgia or breast pain is a common problem affecting women mostly in the age group of 30-50 years. Its prevalence is highly variable ranging from 41% to 79% . Breast Several treatment options have been used for mastalgia, but no particular guidelines are currently followed. In their study, Barros et al. suggested that reassuring mastalgia patients results in satisfaction of 70.2% (n=85) of patients once the possibility of cancer is ruled out . SupportPsychological counseling and psychoeducation-relaxation therapy are reported to play an important and parallel part in the therapy . KinesioDue to the varying opinions prevalent in the literature regarding the psychomotor basis of mastalgia, the absence of any sufficient evidence regarding the association of treatment requirements with psychological status, and the absence of any particular treatment algorithm for mastalgia, this particular study was planned. The study aims to evaluate the psychological status and effectiveness of various treatment options in women presenting with mastalgia.Study settingThis was a prospective comparative study. Consecutive consenting patients who presented to the General Surgery outpatient department of King George’s Medical University, Lucknow, India, with mastalgia from February 1 to November 30, 2021 (the duration of the study was 10 months) were included in this study. The entire group of patients were treated by the same team of surgeons. The data collection proforma is given in the Appendix.Inclusion and exclusion criteriaFemales of all age groups presenting to the General Surgery outpatient department with unilateral/ bilateral breast pain and/or chest wall pain were considered for this study. Pregnant patients , patients with a history of allergy to drugs (as continuing with such patients as a part of the study will be difficult in case of adverse drug reactions), or patients who were lost to follow-up were excluded from the study.ProceduresPsychological AssessmentEach patient was assessed for her psychological status, on her first OPD visit, by the investigators in coordination with the consultant surgeon, using the Depression Anxiety and Stress Scale (DASS-42), a validated questionnaire to assess the negative emotional states of depression, anxiety, and stress status of a patient . This paClinical ExaminationEvaluation of pain severity using the visual analog scale (VAS) score: A whole breast examination and a rollover test were performed for each patient. In a rollover test, the patient is asked to roll over to the opposite side, which allows the breast tissue to fall towards the midline by gravity resulting in flattening of the lateral half of the mammary gland. This helps to differentiate mammary pain from extramammary pain. The severity of pain was assessed using a VAS score. Participants were asked to score the pain they had experienced during the week before arrival at the OPD, from 1 (mild pain) to 10 (worst pain) and the VAS scores were evaluated by the investigators of the study in coordination with the consultant surgeon, during each OPD visit of the patient, and especially mandatorily in the first visit.Other InvestigationsSerum 25-OH vitamin D levels (Highly Sensitive Chemiluminescent Immunoassay), high-resolution ultrasound breasts (HRUSG) , and mammography obtained by  were obtained after their first OPD visit (only for women>35 years). Other investigations were based on the clinical presentation.Categorization of patientsPatients complaining of breast pain might have either a mammary (breast pain) or an extra-mammary  etiology. Even the breast wall pain may have multiple presentations like isolated breast(s) pain not associated with lumps , concurrent breast and chest wall pain, pain with a lump, or pain and tenderness only over the lump, with otherwise normal breast and chest wall. Treatment courses vary largely based on these clinical findings. So, based on clinical findings, the patients were differentiated into five categories. The first category comprised patients with isolated chest wall pain, like costochondritis, rib pain, and neck pain, which is referred to as the chest wall. The second category had patients with isolated breast(s) pain and the third category had patients with co-existing chest wall and breast(s) pain. Patients who had pain associated with a lump(s) were categorized into the fourth category, and the fifth group had patients with pain and tenderness over a lump with normal breast and chest wall Table .ManagementBased on the VAS scores at the time of screening, patients were distributed into two groups: Group A (VAS ≤ 4 or pain not interfering with routine activities) and Group B (VAS > 4 or pain interfering with routine activities). Patients in Group A were reassured and asked to report if their pain did not subside. Patients in Group B underwent treatment and management as given below.Treatment should be ideally escalated from non-hormonal to hormonal therapy, and from simpler to more complex options. Hence, the patients were started on either NSAIDs or EPO+vitamin E. Following this, they were started on hormonal options, beginning with tamoxifen (lesser side effects), followed by danazol (more side effects). Ormeloxifene is a comparatively newer option, so was kept at the last.Patients of Group B were distributed into the topical NSAIDs group or EPO+Vitamin E group using the purposive sampling method. VAS scores of patients taking either of the medicines were re-evaluated and based on the scores, the patients were managed as shown in Figure The patients taking topical NSAIDs, who reported a decrease in VAS scores by ≥ 50% in a week were asked to continue the same medication for 15 days and were re-evaluated after two months. If the patient reported resolution of pain, they were considered successfully treated, else were prescribed EPO 1 gm thrice a day and vitamin E 400 mg once a day for a month and managed further. The patients on NSAIDs, who reported a decrease in VAS scores by < 50% were switched over to EPO+vitamin E for a month and managed further.The patients on EPO+vitamin E who reported a decrease in VAS scores by ≥ 50% were asked to continue the same medications for two months and were re-evaluated after the two months. If the patient reported resolution of pain, they were considered successfully treated, or else were switched over to tablet tamoxifen 10 mg once a day for a month and managed further.The patients on tamoxifen, who reported a decrease in VAS scores by ≥ 50% were asked to continue the same medication for two months and were re-evaluated after the two months. If the patient reported resolution of pain, they were considered successfully treated, or else were switched over to tablet danazol 100 mg once to twice a day for a month. The patients on danazol, who reported a decrease in VAS scores by ≥ 50% were asked to continue the same medication for two months and were re-evaluated after the two months. If the patient reported resolution of pain, they were considered successfully treated, else were switched over to the tablet ormeloxifene 30 mg twice a week for a month.No treatment modality was continued for more than three months.Ethical approvalThe study was approved by the Institutional Ethics Committee of King George’s Medical University, Lucknow (ECR/262/Inst/UP/2013/RR-19) (reference number: 102ndECMIIA/P8). Written informed consent (in either English or Hindi) was taken from all patients before enrolling them in the study.Statistical analysisStatistical analysis was performed using IBM SPSS Statistics for Windows, Version 23.0 . All data was expressed as mean±SD. A non-parametric test (Chi-square test) was used to compare the DASS-42 category-wise score of the patients with their respective VAS scores at the first visit and duration of pain at the first visit. p-value<0.05 was considered significant. A total number of 106 patients  were enrolled in the study Figure . The meaClinical examinationOf the 106 patients, 82.08% (n = 87) had a cyclical pattern of pain, whereas 17.92% (n = 19) had a non-cyclical pattern of pain. Eighty-three 78.30%) patients presented with bilateral pain, whereas 14.15% (n = 15) had pain localized to the left side and 7.54% (n = 8) had right-sided pain. Out of 106 patients, 34.90% (n = 37) had isolated breast(s) pain, 14.15% (n = 15) had isolated chest wall pain, 50% (n = 53) had both breast(s) and chest wall pain and 0.94% (n = 1) had pain with an associated lump. The nature of pain was dull in 48.11% (n = 51) and pricking in nature in 21.70% (n = 23). The mean duration of pain of patients at the first visit was 70.13±18.29 weeks, which ranged from one week to 159 weeks. Four patients reported breast cancer in first-degree relatives  patients had normal scores, 7.54% (n = 8) had mild, 10.38% (n = 11) had moderate, 3.77% (n = 4) had severe, and 5.66% (n = 6) had extremely severe scores for depression. For anxiety, 66.03% (n = 70) had scores in the normal range, 11.32% (n = 12) had mild scores, 10.38% (n = 11) had moderate scores, 5.66% (n = 6) had severe scores, and 6.60% (n = 7) had extremely severe scores. For stress, 66.98% (n = 71) had normal scores, 14.15% (n = 15) had mild scores, 13.20% (n = 14) had moderate scores, 4.71% (n = 5) had severe scores, and 0.94% (n = 1) had extremely severe scores  patients completed the treatment until resolution. Of the 88 patients, 15 (17.05%) had a VAS score <4, and they were reassured without any treatment. On telephonic follow-up after seven days, the pain subsided in 13 (86.67%) patients, and two (13.33%) were started with further courses of treatment. Out of the remaining 75, 36 (48%) were given vitamin D supplementation, along with the treatment or as the sole treatment in case of only chest wall pain with associated vitamin D deficiency. Out of them, 15 (41.67%) had only chest wall pain. So, it was the sole treatment in them. All of them had resolution of their pain after the course of vitamin D. The rest 21 (58.33%) had been started on Vitamin D along with the other treatment options.Forty-three patients were started with NSAIDs as the first line of treatment. Of them, 29 (67.44%) were completely treated, and one was operated for fibroadenoma. The rest 13 (30.23%) were moved to the second line of treatment, that is, EPO+vitamin E. Out of 13, three (23.07%) reported complete resolution. The rest 10 (76.92%) were started with the third line of treatment, tamoxifen 10 mg. The pain subsided completely in eight (80.00%) and the remaining two (20.00%) were switched over to danazol 100 mg, which was followed by complete resolution of pain subsequently.Thirty-two patients were started on EPO+vitamin E as the first line of treatment. While 29 (90.63%) were completely relieved, three (10.34%) were switched to tamoxifen. While two (66.67%) of them were completely relieved, the remaining one was successfully treated using danazol. Menstrual irregularity was observed as a side-effect in one patient (33.33%) taking danazol for two months Table .Association of psychological status with treatmentPatients requiring a switchover to higher treatment options or who did not respond to initial lines of treatment had their initial DASS-42 scores higher than those who responded to initial lines of treatment Figure , Table 4In the current study, the majority of patients, i.e. 87 (82.08%) had cyclical mastalgia, compared to the 19 (17.92%) who had non-cyclical mastalgia. Thirty-seven (34.90%) patients had isolated breast(s) pain, 15 (14.15%) had isolated chest wall pain, 53 (50%) had both breast(s) and chest wall pain, and one (0.94%) had pain with an associated lump. Our findings are in affirmation with the available literature, which also suggests cyclical mastalgia to be more common as compared to non-cyclical ,13. The psychological assessment of the patients elicited normal scores for depression anxiety and stress in the majority. The pain severity (VAS scores), and the duration of pain on the first visit were found to have no significant relationship with depression, anxiety, or stress levels DASS-42 scores) Figures -4. The r2 scores For patients with low VAS scores (VAS< 4), reassurance and counseling proved to be beneficial, with 13 out of 15 (86.67%) reporting resolution. Reassurance and counseling were also found to be beneficial in a study by Barros et al. .Twenty-nine of 43 patients (67.44%) who received topical NSAIDs as the first line of treatment, reported complete resolution of pain. In a study by Colak et al., follow-up after six months showed pain score in patients of cyclic mastalgia decreased by 5.87 ± 1.22 on NSAID administration as compared to the placebo group, which showed a very little decrease by 1.30 ± 1.34, and in patients with non-cyclic mastalgia, it decreased by 6.33 ± 1.34 on NSAID administration as compared to placebo group where it decreased by 1.12 ± 1.11 . Also, aEight out of 43 (18.60%) of the NSAID arm and two out of 32 (6.25%) of the EPO+vitamin E arm were completely relieved of their pain using tamoxifen, thus showing an 80% (eight out of 10) success rate in cases resistant to both NSAIDs and EPO and 66.67% (two out of three) success rate in cases resistant to EPO. We did not observe any side effects of tamoxifen in our study as it was administered for a short term of ≤ three months. The two non-responders (4.65% of the NSAID arm) to tamoxifen from topical NSAIDs as the first line treatment group and the one (3.12% of the EPO+vitamin E arm) from the evening primrose oil plus vitamin E group, were successfully relieved of pain using danazol. Danazol is far more effective than a placebo in several studies ,32. In aPain in all the patients subsided by initial lines of treatment, hence no patients were switched over to ormeloxifene.We did not find a psychoneurotic basis for mastalgia in our study. The DASS-42 scores had no significant correlation with pain or the duration of pain at the initial visit. But, an indirect indication of the psychoneurotic basis of mastalgia can be seen in Figure Strengths and limitations of the studyOur study attempts to formulate an algorithm-based approach for patients with mastalgia, which has been largely lacking, despite abundant treatment options available. This study also emphasizes that the majority of women can be treated with reassurance, topical NSAIDs, and EPO, while the use of hormonal treatment can be reserved for a selected few.The current study used a purposive sampling method; hence, the possibility of selection bias can't be entirely ruled out. Also, the results can't be generalized, as all patients were from the northern part of India. Further studies on different study populations are essential to generalize these results. The number of patients requiring tamoxifen and danazol was extremely low in both groups and hence the role of these drugs couldn't be studied extensively. Ormeloxifene, another popular treatment option for mastalgia, couldn’t be tested in our study since all patients resolved by earlier lines of treatment. Also, our study didn’t explore the options of formulation of a treatment algorithm that can be safe at all steps for pregnant women and for those who were allergic to drugs, due to their exclusion from the study population.Future studiesThe association of psychological status with treatment lines couldn't be generalized in our study due to the fewer number of patients in the higher treatment lines, which in turn was due to the algorithmic design of this study. So, options for studies with different designs and higher sample sizes should be explored further. Moreover, further studies are required on other groups of the population to generalize the results. Even within India, populations in the different regions vary a lot in characteristics. For example, South India is inhabited mostly by Dravidian population while North India is primarily inhabited by Indo-Aryan population. Hence, even for national algorithms to be in place, further studies are essential. Also, our study couldn't elicit a clear-cut relation between psychological status and mastalgia; hence, further studies with larger sample sizes are required to be conducted. To probe into the possible cause behind this, more studies are required to be conducted. Exploration of the options for the formulation of a treatment algorithm that can be safe at all levels for pregnant women and individuals who are allergic to drugs should be done in the future, with the collaboration of obstetricians and pharmacologists.Differentiating mammary from extramammary pain is important before initiating any treatment in patients with mastalgia. Reassurance and counseling, along with lifestyle modifications, appropriate diet, and adequate breast support are sufficient in the majority of patients with low VAS scores. Most of the patients were relieved of mastalgia with NSAIDs or EPO and vitamin E in our study, with very few requiring second-line hormonal treatment like tamoxifen and danazol. The algorithm proposed by us, which included starting with non-hormonal simpler pharmacotherapies like NSAIDs or EPO and vitamin E (supplemented by vitamin D supplementation in case of its deficiency), followed by hormonal options like tamoxifen (fewer side-effects) succeeded by danazol (more side-effects), proved to be quite successful in treating patients, with complication noted in just one out of 88 patients. The duration or severity of pain did not correlate with the psychological condition of the patient, but this doesn’t rule out the importance of psychological evaluation in patients of mastalgia, because it was also observed in our study that patients who required further upgradation in treatment lines, were also the ones having worse DASS-42 scores.


Regression analyses were conducted to assess the weighted contribution of psychological and procedural factors to POH. In individuals with POH, mental ailments, preexisting headaches, premorbid chronic pain syndromes, and higher somatization tendencies were found to be significantly more common. POH was predicted by the number of premorbid psychosomatic symptoms, preexisting mental ailments, and premorbid chronic pain syndromes. Depression and anxiety were predicted by low emotional stability. Additionally, the number of premorbid psychosomatic symptoms predicted depression, anxiety, and overall psychological burden. It was observed that the reported symptoms of headache might fit into the classification of chronic postsurgical pain (CPSP) rather than being classified as secondary headaches after craniotomy. Premorbid psychological factors were found to play an important role in the emergence of POH in VS, particularly after microsurgery via the retrosigmoid approach. Therefore, it is suggested that psychological screening be incorporated into the treatment process.Associations between premorbid psychological factors and postoperative headache (POH) after microsurgical treatment via the retrosigmoid approach for vestibular schwannoma (VS) were investigated in this retrospective single-center study. A total of 101 VS patients completed the Rostock headache questionnaire (RoKoKo), the hospital and anxiety scale (HADS-D), and the screening for somatoform disorders (SOMS-2), all of which were used as short self-assessed questionnaires. Fifty-four patients with POH were compared with 47 non-POH patients in terms of premorbid psychological factors, somatization tendencies, and psychological burden using the chi Vestibular schwannoma (VS) is a benign tumor originating from Schwann cells. Located intra- and extrameatal, hearing loss, dizziness, and tinnitus are common symptoms resulting from the tumor’s affection of the vestibulocochlear nerve. A current prospective study suggests that those complications are unlikely to be significantly modified by treatment modality, i.e., observation, microsurgery, or radiosurgery , but preNot surprisingly, the vast majority of past research on POH in the neurosurgical field has been focused on discussing medical reasons as well as procedural factors, such as intracranial bone dust ,9,10,11,Psychological symptoms in VS patients, like depression and anxiety, have all been examined for the postoperative state ,23,24. EThe aim of this study is to: (1) characterize premorbid psychological factors in patients with VS who develop POH; (2) determine the weighted contribution of these variables to the occurrence of POH; and (3) find premorbid predictors for postoperative anxiety and depression in individuals with POH. Results might be helpful for the management of POH in VS by shining light on psychological targets that can be addressed before surgery to prevent the emergence of severe POH.Vereinigung Akustikus Neurinom e.V. (a non-profit patient self-help organization) to complete an online survey (SoSciSurvey). Both surveys ran identically. All participants provided written consent prior to study participation. The study was approved by the Ethics Committee of the University Hospital Halle (No. 2020-008).This study followed a retrospective approach. Inclusion criteria were diagnosis, a minimum age of 18 at diagnosis, surgery via retrosigmoid approach, and German as a native language. Patients who underwent previous surgery or radiation and/or suffered from recurrent VS, as well as patients with oncological diagnoses and neurofibromatosis type 2, were excluded. The study was started in early 2020, which resulted in the recruitment of patients being influenced by the COVID-19 pandemic. Participants were approached directly at the chief resident consultation at University Hospital Halle and after the start of the national lockdown via a call for participation by the POH was defined as a long-term, frequent headache that lasted for more than 3 months after microsurgery. We assessed POH using the Rostock headache questionnaire (RoKoKo) to assign the symptoms to migraine (constant), tension-type headache, or other headaches . It covep-value of 0.05. In the online survey, the option “I don’t know” was given for questions concerning the surgical approach . These answer options were counted as “missing” and were not included in the statistical analysis for group differences.Statistical analysis was carried out using SPSS for Windows Version 25 . Demographic characteristics, including sex at birth and age, premorbid chronic pain syndromes and mental ailments, and scores on the SOMS-2, HADS-D, and TIPI, were compared between participants with and without POH. Distribution was assessed by the Kolmogorov–Smirnov test. For clarity, all summary statistics are reported as means with a standard deviation (SD). Categorical features were summarized with frequency counts and percentages. To identify group differences between participants with and without POH, dichotomous data were compared using chi-squared tests. Metric data were compared using Mann–Whitney U tests. For comparisons between different POH groups, Kruskall–Wallis tests were used. Statistical significance was accepted at a 2-criterion was performed using all variables mentioned above. Current depression and anxiety scores were not taken into account, as only premorbid and preprocedural factors are of interest. This statistical approach was based on the work of Peña et al. [F = 0.05 was used as the entry criterion. Goodness-of-fit was assessed by an adjusted R2 as suggested by Cohen [To understand the weighted contribution of psychological variables to POH, a binary logistic regression was conducted. A total of three models were established: Model 1 was formed to account for the potential effects of variables that have been significant predictors in previous studies, such as age at onset, sex at birth, time since surgery, and tumor size. The dichotomous psychological variables premorbid psychological ailments, premorbid chronic pain syndromes, and emotional stability as a psychological trait were included in Model 2. Then, a final stepwise binary logistic regression using the Likelihood ratio Chia et al. . The gooby Cohen .p = 0.074), whereas participants with POH were significantly younger at the time of the survey (p = 0.039). In terms of sex, there were significantly fewer male patients in the POH group . There was no significant difference in time since surgery (p = 0.096). Groups did not differ concerning facial nerve paresis (p = 0.267) and hearing loss after surgery (p = 0.335). With respect to tumor size, a total of seven participants from the online cohort were excluded from the analysis. A group comparison of tumor size among the remaining participants showed no significant difference in Koos grade (p = 0.222). For analysis concerning craniectomy and positioning during surgery, 14 and 10 patients were excluded, respectively. POH patients did not differ from non-POH patients concerning craniectomy (p = 0.095) or positioning during surgery (p = 0.654).A total of 101 patients were included , with 54 participants (53.5%) reporting the existence of POH. A summary of group comparisons can be found in RoKoKo, which differentiates four different types of headaches: paroxysmal (n = 13), constant (n = 15), paroxysmal and constant (n = 19), and other than described (n = 8). A summary of headache types and pain location is shown in n = 4), central (n = 4), or frontal (n = 3) pain. In the constant pain group, the majority of patients reported mostly unilateral pain (n = 8) in the temporal (n = 5) or central (n = 4) regions. Patients experiencing paroxysmal and constant POH reported mostly unilateral pain (n = 16), in some cases alternately during (n = 3) or between attacks (n = 2). These patients described the pain location mainly as temporal (n = 10) or occipital (n = 8). In the “other than described” group, 8 participants reported mostly unilateral pain, and 5 described POH as mostly bilateral.To identify the characteristics of POH, we used the n = 7), pulsing (n = 4), gnawing (n = 3), and burning (n = 1) sensations. In the constant pain group, mostly pulsing (n = 8) and dull (n = 9) pain was reported, followed by a lancinating (n = 6) and burning (n = 1) character. Lancinating (n = 19) and dull (n = 14) pain occurred in most patients with both paroxysmal and constant pain. The “other than described” pain group reported mostly lancinating (n = 8) and dull pain (n = 6) as well.p < 0.001). The most frequently mentioned syndromes were premorbid headache syndromes and chronic back pain, followed by stomach and bowel problems and face and knee pain (p = 0.001), such as difficulty falling asleep or sleeping problems through the night, undefined physical exhaustion, panic attacks, rumination, and in one case even a suicide attempt. No group differences in terms of the existence of premorbid psychological diagnoses were found (p = 0.106). The mentioned diagnoses included Major depressive episodes, burnout syndrome, acute stress disorder, anxiety disorder, and posttraumatic stress disorder (p = 0.048).nee pain . In the disorder . Premorbp < 0.001), somatization index ICD-10 (p = 0.016), and somatization index DSM-IV (p = 0.001) scores, with POH patients reaching higher scores than non-POH patients. The same is shown for current mood in HADS-D scores, with POH patients reporting significantly higher scores in the depression (p = 0.034) and anxiety subscores (p = 0.014) and the total score (p = 0.008). No group differences were found for emotional stability (p = 0.383).p = 0.498), somatization index ICD-10 (p = 0.545), somatization index DSM-IV (p = 0.148), depression (p = 0.222), anxiety (p = 0.537), HADS-D total score (p = 0.535), and emotional stability (p = 0.314), Different headache groups according to the RoKoKo did not differ with respect to symptom count score (χ2(6) = 9.78, p > 0.05 and consequently does not bear significant predictive value for POH. The psychological measures Model 2, however, was statistically significant (χ2(4) = 22.83, p < 0.001 (R2 = 0.25)), with preexisting chronic pain syndromes being a significant predictor. Goodness-of-fit was assessed using the Hosmer–Lemeshow test, indicating a good model fit χ2(8) = 9.53, p > 0.05. In the stepwise regression, which included all variables from Models 1 and 2, variables were added to the model based on their contribution. In the stepwise regression, which included all variables from Models 1 and 2, variables were added to the model based on their contribution. This final model (χ2(3) = 24.23, p < 0.001, (R2 = 0.27)) retained age at onset, premorbid mental ailments, and premorbid chronic pain syndromes as significant predictors for POH (Hosmer–Lemeshow test χ2(7) = 10.64, p > 0.05). According to these results, a younger age at onset as well as the existence of premorbid mental ailments and chronic pain syndromes were shown to be predictive factors for the emergence of POH.The results of all regression models conducted for POH are shown in F = 36.21, p < 0.001. The R2 for the overall model was 0.44 (adjusted R2 = 0.42), indicative of a high goodness-of-fit, according to Cohen [F = 12.13, p = 0.001, R2 = 0.27) with a moderate goodness-of-fit (adjusted R2 = 0.24). HADS-D anxiety scores could be significantly predicted by a high number of symptoms and low emotional stability  = 48.13, p < 0.001, R2 = 0.55), showing a high goodness-of-fit (adjusted R2 = 0.53).Regression analysis for HADS-D scores can be found in to Cohen . A signiIn this pilot study, we analyzed the relationship between long-term POH and premorbid psychological variables as well as the implications of premorbid psychological factors on depression and anxiety levels in patients with VS. The major finding of our investigation was the association between premorbid psychological factors and POH in patients with VS after microsurgical treatment via the retrosigmoid approach. The results indicate that patients with POH are more likely to have premorbid mental ailments like sleep disturbances, panic attacks, and rumination, as well as premorbid chronic pain syndromes such as chronic back pain or primary headache syndromes. These psychological factors seem to weigh more than procedural factors like positioning during surgery. The number of premorbid psychosomatic symptoms is a significant predictor of psychological burden in POH patients, whereas depression and anxiety are also influenced by low levels of emotional stability.Our results are in accordance with preexisting literature regarding premorbid psychological symptoms in VS patients ,26. ThosAn association between current HADS scores and headache impairment was demonstrated by Carlson et al. . SimilarIn our study, we classified POH as a secondary headache syndrome. In the new international classification of diseases (ICD-11), another category is being introduced: chronic postsurgical pain (CPSP), which could also fit POH. CPSP is usually described as neuropathic pain with a traumatic cause, and risk factors include female sex at birth, young age, the existence of preoperative pain conditions, and perioperative factors such as duration and type of surgery . Depressp = 0.048). It is therefore conceivable that, at least in some of these patients, POH may be a continuation of preoperative symptoms. However, this also implies that surgical treatment was not able to abolish these, resulting in postoperative chronic headaches largely indistinguishable from patients with newly developed POH. This latter group amounted to 61.1% of POH patients, underscoring that POH is a relevant clinical issue partly independent of preoperative status. Further studies should investigate details of qualitative characteristics as well as the evolution over time of preexisting headaches to potentially identify a corresponding subgroup. It is also worth noting that some participants mentioned experiencing premorbid headache syndromes when asked about premorbid pain syndromes, which could potentially impact the results regarding this variable. However, since group differences for all SOMS-2 measures were still evident between the POH and Non-POH groups, we can infer that these differences might be unrelated to the presence of premorbid headache as reported in the specified variable.A comparison between patients with and without POH revealed a significantly higher incidence of headaches before surgery . Anonymous participation is also prone to fraud .Employing a retrospective approach in this study introduces the possibility of memory bias. The average duration between the survey and surgery was relatively extensive. This extended time frame offers the advantage of examining the long-term effects of POH. However, it also creates an environment conducive to distorted memories of the period preceding the surgery. Anxiety and depression can influence memory biases, leading to misrepresentations of daily emotional experiences and a tendency to recall more negative affect . Though Overall, the distinction between psychological and biological variables has not been sharp enough. Sleep disturbances and physical exhaustion can be psychological symptoms but can also be related to somatic illnesses or prodromal symptoms. Because of the retrospective approach, there were no objective measures for these variables. We simply had to trust the reliability of the respondents.POH is a major problem for patients after microsurgical treatment in VS. Our study suggests that younger patients with female sex at birth, premorbid somatization tendencies, and mental ailments might be at a higher risk of developing POH. The results indicate the classification of POH as CPSP rather than a secondary headache syndrome, which can be preceded by high somatization tendencies and mental ailments. A high number of premorbid psychosomatic symptoms predicts postoperative psychological burden in patients with POH, and depression is also associated with neuroticism. Future studies should verify our findings to be generalizable with a prospective approach to avoid memory bias for premorbid factors. There should also be a sharper distinction between psychological and biological factors. Further, larger cohorts with respect to different surgical procedures should be studied. As a result, the preoperative examination should include a standardized psychological examination. Finally, VS patients at risk for POH should get the opportunity to choose psychological support during treatment and the follow-up period.


Other secondary endpoints, including measures for disability , also differed. Thus, in non-responder patients with CM, BoNT-A significantly reduced migraine days when administered according to the “follow the origin of maximum pain” approach using SjBoT injection paradigm.In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of an individualized technique of subcutaneous injection of botulinum toxin type A (BoNT-A) targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine (CM). Patients who had not previously responded to at least two treatments of intramuscular injections of BoNT-A were randomly assigned (2:1) to receive two subcutaneous administrations of BoNT-A (up to 200 units) with the SjBoT injection paradigm or placebo. Following the skin area where the maximum pain began, treatment was given in the trigeminal or occipital region bilaterally. The primary endpoint changed in monthly headache days from baseline to the last 4 weeks. Among 139 randomized patients, 90 received BoNT-A and 49 received placebo, and 128 completed the double-blind phase. BoNT-A significantly reduced monthly headache days versus placebo (−13.2 versus −1.2;  Chronic migraine (CM) is a disabling neurological disorder affecting 1.4–2.2% of the world’s population . TreatinHowever, as many as 30.4% of CM patients do not respond to treatment with intramuscular injections of BoNT-A, and many also report that they are not satisfied with the treatment . To imprThe characteristics of the 139 patients with CM enrolled in this study are summarized in p < 0.0001. The reduction in monthly headache days was −11.6 in the trigeminal group versus −14.8 in the occipital group (p < 0.001) in the BoNT-A treatment. , HAMA scores went from 10.56 ± 11 to 8.14 ± 6.46 (p = 0.048). On the other hand, HARS scores went from 18.56 ± 12.49 at baseline to 15.76 ± 12.16 (p = 0.952) 180 days after treatment in the trigeminal group; in the occipital group, HARS scores went from 19.55 ± 12.7 to 14.17 ± 12.28 (p = 0.080). A significant difference in pain intensity and migraine-related disability was observed in the BoNT-A treatment group: in the trigeminal group, the VAS score went from 9.09 ± 1.46 at baseline to 8.21 ± 2.22 at 180 days (p = 0.011); in the occipital group, the VAS score went from 8.86 ± 1.78 to 6 ± 2.69 (p = 0.007). As for migraine-related disability, MIDAS went from 21.96 ± 16.32 at baseline to 7.59 ± 6.24 after treatment (p = 0.028) in the trigeminal group. On the other hand, in the occipital group, MIDAS went from 29.4 ± 22.19 to 8.14 ± 6.47 (p = 0.001)  . AdverseThis is the first randomized, double-blind, placebo-controlled study demonstrating the efficacy and safety of the “follow the origin of maximum pain” approach using subcutaneous injections of BoNT-A targeted (SjBoT) to the occipital or trigeminal skin area in non-responder patients with chronic migraine. Our results show that subcutaneous injections of BoNT-A targeted to the skin area of maximum headache pain origin significantly reduce migraine frequency, pain severity, and disease disability.The efficacy of the individualized SjBoT injection paradigm is based on the antinociceptive effect of subcutaneous injections of BoNT-A and on the targeted regional administration of BoNT-A using the “follow the origin of maximum pain” approach.Consistent with our results, several animal studies confirmed the antinociceptive effects of subcutaneous injection of botulinum toxin type A ,19. In cIn the context of migraine, extracranial application of BoNT-A was shown to inhibit mechanical transduction in the suture branches of meningeal nociceptors, thus inhibiting mechanical nociception in peripheral trigeminovascular neurons ,23. The Another important contributing factor to the efficacy of the SjBoT injection paradigm for the prevention of CM is the regional administration of BoNT-A in the cutaneous area of the maximum pain’s origin. The latter is the area of ictal cutaneous allodynia during migraine attack, which represents the clinical expression of peripheral nociceptor sensitization . Higher The strength of this pilot study is intrinsically linked to its design. Another important finding is that the individualized SjBoT injections paradigm appears to be a safe treatment. The limitation is that this is a single-center study, and other limitations are due to the small number of patients, the lack of evaluation of long-term effects of repeated administration of the treatment, and the administration of a single placebo treatment. However, in view of the severity of migraine in these patients and the poor response to placebo treatment, it was appropriate to administer a single dose of placebo. Another possible limitation is that the placebo response was low compared with what was observed in the PREEMPT studies ,31. ThisIn conclusion, the data from this study demonstrate that the “Follow the Origin of Maximum Pain” approach using the individualized SjBoT paradigm may be a useful option for the preventive treatment of CM in non-responder patients and suggests the need to do further similar studies to confirm our results.This is a single-center, double-blinded, randomized, placebo-controlled interventional trial conducted at a tertiary Headache Centre of the academic hospital in Catanzaro, Italy.Prior to inclusion in the study, written informed consent was obtained from all patients, and the study was approved by the local Ethics Committee according to the Declaration of Helsinki.(i)Men or women between 18 and 50 years of age with CM, satisfying the diagnostic criteria of the International Classification of Headache disorders (ICHD-3) ;(ii)Failure of at least two treatments with intramuscular injections of BoNT-A in the cranial/pericranial muscles performed more than 6 months ago;(iii)For women of child-bearing potential, the use of highly effective contraception.Overuse of drugs was defined as taking simple analgesics for ≥ 15 days, or other types of drugs or combinations of types for ≥ 10 days.(i)Presence of diseases interfering with neuromuscular function;(ii)Presence of psychiatric disorder;(iii)Other primary/secondary headaches.Tension-type headache was allowed if the patient could clearly distinguish the two types of attack.The primary endpoint was considered the change in monthly headache days. Secondary outcomes were: change in Migraine Disability Assessment (MIDAS) questionnaire, Hamilton Anxiety Rating Scale (HARS), Beck Depression Inventory-II (BDI-II) scores, change in pain intensity, all compared with baseline.At baseline, each patient provided a diary of headache days in the previous month. All patients underwent thorough clinical data collection to identify the skin area of onset of maximum headache pain and the characteristics of headache. The 12-item Cutaneous Allodynia Symptom Checklist (ASC-12) was administered during a headache attack. Pain and disability were assessed using the Visual Analog Scale (VAS) from 0 to 10, and the MIDAS questionnaire. Mood and anxiety were assessed with the BDI-II and the HARS scores. At follow-up, each patient was evaluated every 30 days until 180 days after treatment. The patient reported headache day data for the previous month and underwent the same tests completed at baseline evaluation. All patients were allowed to use medication for the acute migraine attack and preventive therapy at the same levels as before baseline, but other methods of pain control or new preventive treatments were prohibited. The principal investigator, who was not involved in treating and assessing the outcome of patients, randomized the eligible patients into BoNT-A treatment or placebo group in a 2:1 ratio; the therapist administered the treatment in the outpatient clinic; the investigator who assessed the outcome avoided physical contact between patients during the treatment; the patients were instructed to fill in diaries recording headache occurrence before treatment and during months post-treatment. The investigator who assessed outcome, the patients, and the therapist were all blinded. The blinded investigator created the database from the headache diaries filled by the patients. Patients were randomized to BoNT-A or placebo treatment , then paThis approach consisted of regional administration of BoNT-A into the skin area of origin of maximum pain in patients with CM. The skin area of maximum cephalalgic pain was thus the target of subcutaneous injections of ONA, and according to this feature, patients were assigned to the trigeminal or occipital treatment with SjBoT paradigm .The BoNT-A (onabotulinum) and placebo treatment consisted of between 20 and 40 subcutaneous injection sites placed at a mutual distance between 1.5 cm and 2.0 cm into the skin area of onset of maximum pain according to the SjBoT injection paradigm: the skin area innervated by the first branch and a small part of the second and third branch of the trigeminal nerve for treatment of the trigeminal region A,B; the t-test for age and BMI and (ii) the Mann–Whitney test for BDI, HARS, VAS, and MIDAS. Differences between baseline and post-treatment (t180) in the BoNT-A group—separately for patients in the trigeminal and occipital group—of BDI, HARS, VAS, and MIDAS were assessed with a single-tailed Wilcoxon rank-sum test. Evaluation of differences in the primary endpoint, i.e., the reduction in the number of headache days per month and mean change in total headache days per month, between patients in the BoNT-A group and those in the placebo group, separately for trigeminal and occipital patients, were performed with Fisher’s exact test and the Mann–Whitney test. The change in the secondary endpoint at each time point, t30, t60, t90, t120, t150, t180, compared with baseline in the BoNT-A treatment  groups were analyzed with a single-tailed Wilcoxon test. A statistically significant result was considered if p < 0.05, and when not explicitly specified, all p-values were two-tailed.Statistical analysis was performed using Statistical Package for Social Science software  for Macintosh. Differences in frequency distributions between patients in the BoNT-A treatment and placebo groups, separately for patients in the trigeminal and occipital groups—of (i) sex and (ii) allodynic and non-allodynic patients—were assessed using the Chi-square test. Regarding demographic and clinical data, the comparison of patients in the BoNT-A and placebo group was separate for patients treated in the trigeminal or occipital skin area at baseline and post-treatment (t180) using (i) the two-sample unpaired


Locomotive syndrome (LS) is characterized by reduced mobility. Clinical decision limit (CDL) stage 3 in LS indicates physical frailty. Lumbar spinal canal stenosis (LSS) is one of the causes of LS, for which lumbar surgery is considered to improve the CDL stage. This study aimed to investigate the efficacy of lumbar surgery and independent factors for improving the CDL stage in patients with LSS.This retrospective study was conducted at the Department of Orthopaedic Surgery at our University Hospital. A total of 157 patients aged ≥ 65 years with LSS underwent lumbar surgery. The 25-Question Geriatric Locomotive Function scale (GLFS-25) was used to test for LS, and the Timed Up and Go test (TUG) was used to evaluate functional ability. Lower limb pain was evaluated using a visual analog scale. Patients with at least one improvement in the CDL stage following lumbar surgery were included in the improvement group. Differences in lower limb pain intensity between the groups were evaluated using the Wilcoxon rank-sum test. The Spearman’s rank correlation coefficient was used to determine correlations between Δ lower limb pain and Δ GLFS-25. Logistic regression analysis was used to identify factors associated with improvement in LS.p = 0.0107). Δ GLFS-25 was significantly correlated with Δ lower limb pain . Multiple logistic regression analysis revealed that TUG and age were significantly associated with improvement in LS .The proportion of patients with improved CDL stage was 45.1% (improvement/non-improvement: 32/39). Δ Lower limb pain was significantly reduced in the improvement group compared with that in the non-improvement group (51.0 [36.3–71.0] vs 40.0 [4.0–53.5]; Lumbar surgery effectively improved the CDL stage in patients with LSS. In addition, TUG was an independent factor associated with improvement in the CDL.The online version contains supplementary material available at 10.1186/s12891-023-06966-x. The number of older adults who require nursing care is increasing in Japan, along with aging of a large proportion of the population. Musculoskeletal disorders resulting from fractures and falls and joint diseases are the most common causes of nursing care and can result in mobility loss . In 2007The relationship between lumbar spinal canal stenosis (LSS) and LS has recently attracted much attention in the field of spinal diseases . LSS is The Timed Up and Go test (TUG) is an objective measure of functional disability that can be used to evaluate various activities such as standing, accelerating, walking, decelerating, and turning, which are often limited in patients with lumbar degenerative diseases . TUG canPrevious studies have reported that surgical treatment of knee joint  and hip n = 56) and patients with missing data (n = 30) were excluded. Finally, patients in CDL stage 3 were included in this study (n = 71).This retrospective study was conducted between May 2020 and April 2021 at the Department of Orthopaedic Surgery at University Hospital, and 157 patients aged ≥ 65 years with lumbar spinal stenosis who underwent lumbar spinal surgery without serious complications (such as ischemic heart disease or stroke) were enrolled. The inclusion and exclusion criteria are shown in Fig. This study was conducted following the Declaration of Helsinki and was approved by the Ethics Committee of the University. Consent to participate in the study was obtained using an opt-out approach.A physical therapist performed physical function tests, and the patients completed the questionnaire. Age, sex, BMI, TUG, trunk and limb skeletal muscle mass, grip strength, life-space assessment (LSA), prognostic nutritional index (PNI), low back pain, lower limb pain, lower limb numbness, surgical method, and symptoms of lumbar spinal stenosis were adopted as survey items for preoperative factors related to the improvement in LS. Furthermore, the 25-Question Geriatric Locomotive Function scale (GLFS-25) and JOA Back Pain Evaluation Questionnaire (JOABPEQ) were used to examine patients before and after lumbar spinal surgery.The TUG was conducted using a stopwatch to measure the time elapsed from when the subject's body moved to the time they turned at a cone 3 m away and returned to sitting on the chair. A chair with a height of 42.0 cm and elbow rests was used. The subject was given the following instruction: “Please get up from the chair, walk as fast as possible, turn at the cone 3 m ahead, and sit on the chair again. You may turn in either direction.”Skeletal muscle mass was assessed using the bioelectrical impedance method . All patients were assessed on the day of admission. The participants grasped the handle of the analyzer with embedded electrodes and stood on a platform with the soles of their feet in contact with the electrodes (two electrodes each were placed on the feet and hands).Grip strength was measured using a Smedley-type grip strength meter . The participants were instructed to grip the strength meter as firmly as possible after hearing the signal. They were instructed as follows: “Please hold the grip strength meter for 3 s.” The right side was measured twice, and the maximum value was adopted.The LSA was originally developed as a simple questionnaire to assess physical activity in older adults. It is a clinically useful index that has been utilized in clinical practice and research . The totThe PNI scale reflects a patient’s inflammatory and nutritional status and is associated with postoperative complications in spinal diseases , 16.Low back pain, lower limb pain, and lower limb numbness were evaluated using a visual analog scale (VAS), with a score of 100 indicating extreme pain and 0 indicating no pain.The GLFS-25 test focuses on physical pain and ADL in the preceding month. For this study, each item was scored from "no disability" (0 points) to "severe disability" (4 points), and the total score was used to evaluate the CDL stage of the LS patient. Scores were classified as follows: stage 1, ≥ 7 points to < 16 points; stage 2, ≧16 points to < 24 points; and stage 3, ≧24 points .The JOA developed the JOABPEQ, a quality-of-life assessment specific to lumbar spine disease that uses patient-oriented and self-reported functional status. The JOABPEQ is a disease-specific tool consisting of 25 items corresponding to five subscales: low back pain, lumbar spine function, walking ability, social function, and mental health. The score for each subscale ranges from 0–100, with higher scores indicating better conditions .All statistical analyses were performed using JMP version 15.0 statistical software . The GLFS-25 was used to evaluate the CDL stage. Patients with preoperative CDL stage 3 were included in the study, and those with at least one improvement in the CDL stage after lumbar spinal surgery were included in the improvement group . The patp < 0.05. All data are expressed as the median (interquartile range) and range.The Wilcoxon rank-sum test was used to compare the improved and non-improved groups. Logistic regression and decision tree analyses were used to investigate the preoperative factors associated with improvements in LS. The Spearman rank correlation coefficient was used to determine correlations between Δ lower limb pain, Δ lower limb numbness, Δ low back pain, and Δ GLFS-25. In all cases, statistical significance was set at Of the 157 participants who met the eligibility criteria for this study, 71 patients’ data were analyzed after applying the exclusion criteria. Patient characteristics are shown in Table Lumbar spinal surgery improved the mean GFLS-25 score from 48.8 preoperatively to 30 postoperatively. At 3 months postoperatively, the rates of CDL stages 0, 1, 2, and 3 were 7%, 18.3%, 19.7%, and 55%, respectively. In total, the proportion of patients with improved CDL stage was 45.1% (32/71)  .The TUG time and age were significantly associated with improvement in LS (1) Table . LSA, BMA decision tree algorithm was used for variables related to improvements in LS, including age, sex, BMI, LSA, PNI, handgrip strength, and TUG time. In the decision tree analysis, the TUG time was selected as the first divergence variable and LSA was selected as the second divergence variable. Among patients with TUG time < 12.4 s, CDL stage 3 was improved in 66.7%, and LSA was the second divergence variable in patients with TUG ≥ 12.4. Patients with a TUG time ≧12.4 s and LSA ≥ 40 showed improvement from CDL stage 3 by 46.2%. Among patients with reduced physical function, CDL stage 3 was improved in 46.2%, with an LSA score of 40 or higher . Low back pain and lower limb numbness in the improvement group were not significantly higher than those in the non-improvement group   in patients with CDL stage 3. The VAS score for lower extremity pain was significantly improved in the group with an improvement in the CDL stage. Moreover, the Δ GLFS-25 was significantly correlated with the Δ VAS of all pain scales. Thus, the improvements in LS might have been associated with a reduction in pain. The reduction in pain achieved by lumbar spinal surgery improved the ADL and CDL stages. Furthermore, the preoperative TUG time was the most relevant factor for the postoperative results. The patients with good physical function can expect to improve their stage of locomotive syndrome in CDL 3.LS is caused by various orthopedic diseases, resulting in reduced quality of life and shortened expectancy of healthy life . Fujita Moderate physical activity is important for maintaining and improving life functions and preventing disease progression, disability, and frailty in older adults –23. In aThis study aimed to identify preoperative factors associated with the improvement of CDL stage 3 in patients with LSS. In the decision tree analysis, the preoperative factor most associated with LS improvement was the TUG time. In this study, five of 71 patients (7%) got cured of their LS 3 months after lumbar spinal surgery Table . The medThis study has some limitations. First, it was a single-center study. Second, owing to the small sample size. I excluded thirty patient's data in this study because of missing data. There is a possible source of bias. Third, we assessed LS using only the GLFS-25; however, this is difficult to assess by two-step and stand-up tests in patients with the severe LS. Kato et al. showed that the use of GLFS-25 assessment was appropriate for patients with several LS and musculoskeletal diseases requiring surgery .This study showed that improvement in the low back and lower limb pain through lumbar spinal surgery might be beneficial for improving CDL stage 3. TUG time was an independent factor associated with the improvement of CDL stage 3 in patients with LSS.Additional file 1: Supplementary Table 1. Comparison between the two groups before and after surgery.


Six treatments with mild water-filtered infrared-A WBH over a period of three weeks with at least one day in between treatments were applied. On average, the maximum temperature was 38.7 °C for a duration of approximately 15 min. The control group received exactly the same treatment except that an insulating foil between the patient and the hyperthermia device blocked most of the radiation. Primary outcome was pain intensity measured by the Brief Pain Inventory at week 4. Secondary outcomes included blood cytokine levels and FMS-related core symptoms and quality of life. Pain intensity at week 4 was significantly different between the groups in favor of WBH (p = 0.015). A statistically significant pain reduction in favor of WBH was also found at week 30 (p = 0.002). Mild water-filtered infrared-A WBH effectively reduced pain intensity at the end of treatment and follow-up.The challenging treatment situation of patients with fibromyalgia syndrome (FMS) requires additional therapy options. The effects of water-filtered infrared-A whole-body hyperthermia (WBH) versus sham hyperthermia on pain intensity were investigated in an outpatient setting within a two-armed randomized sham-controlled trial.  Fibromyalgia syndrome (FMS) is a chronic disorder characterized by chronic widespread pain, physical and/or mental fatigue, and nonrestorative sleep as core symptoms. It is often accompanied by various somatic and psychological symptoms such as headache, bowel problems, morning stiffness, anxiety, and depression. The worldwide prevalence varies between 0.2 and 6.6% . Women wThe treatment situation of FMS is often perceived as insufficient ,10,11,12WBH works by increasing body-core temperature to create an artificial fever-like state . AdverseThe main objective of this randomized sham-controlled trial was to investigate the effect of mild wIRA-WBH on pain intensity in patients with FMS in an outpatient setting.https://clinicaltrials.gov/ct2/show/NCT05135936 (accessed on 13 February 2023), and performed according to the declaration of Helsinki applying good clinical practice standards.This prospective, monocentric, randomized, sham-controlled, single-blinded, 2-armed, parallel group trial was conducted from November 2020 to December 2021 at the Sozialstiftung Bamberg, Bamberg, Germany. The study was approved by the Ethics Committee of the Bayerische Landesärztekammer , registered on clinicaltrials.gov  aged between 18 and 70 years with a medically confirmed diagnosis of FMS additionally reviewed by a physician according to ACR 2016 criteria during the screening visit and an average pain intensity of ≥4.0 were eligible. The latter was recorded via a pain diary, measuring the pain level four times a day 14 days prior to the eligibility assessment. Main exclusion criteria were severe somatic and psychiatric comorbidities, other chronic pain syndromes, the intake of opioids, cannabis, and immunosuppressive drugs, contraindications for hyperthermia such as body temperature >37.5 °C, heart failure, previous experience with WBH, or the participation in other clinical intervention studies see .After being assessed as eligible by the study doctor, patients were randomly assigned to either the intervention or the control group by the study coordinator (SC). For that purpose, the study coordinator prepared opaque sealed envelopes containing either “A” (for intervention) or “B” (for control) in a 1:1 ratio with a block size of 10. The SC asked the patients to select one envelope, open it and to say out loud the containing letter, which was then protocolled. The meaning of the letters and group allocation was blinded to the patients, study doctor, and those being involved in the assessment of outcomes  but not to the SC and therapists.Participants assigned to the intervention group received a total of six sessions with mild wIRA-WBH of 60 min over a period of three weeks with at least one day between each intervention session.The IRATHERM1000 hyperthermia device was used for this purpose  and can be adjusted in 5% intervals by a control panel (2) during the heating-up phase. When reaching the target temperature, irradiance was decreased to 40% (560 W/m2) to maintain body-core temperature until the end of the 60-min treatment period (plateau phase). This led to a further small increase in temperature in most of the subjects. Deviations from the planned irradiance were made according to the needs of the participants. While being treated subjects laid undressed on the device being covered by a white sheet and a reflection foil.The device stands out for its open design and lying comfort. It has six halogen radiators arranged longitudinal with three on each side including water. The resulting spectrum is called water-filtered infrared-A (wIRA), with typical absorption lines of water and free of infrared B and C. For wIRA, the relationship between irradiation of the skin and deeper lesions is much more favorable compared to conventional technical IR-devices. Maximum irradiance is 1400 W/mol panel B for eac2) were recorded continuously during the entire session and could be viewed at any time by the therapist, but not by the participant. After treatment, participants rested for about 30 min (resting-phase). Thus, one complete intervention was approximately 1.5 to 2 h. Subjects were permanently supervised and a physician was always on call. A discontinuation criterion of the treatment was a body-core temperature of more than 40 °C.Rectal and axillar temperature, pulse and oxygen saturation . Clinical characteristics were captured at baseline (week 0), one week after the end of treatment (week 4/postintervention), and two and six months after the end of the treatment .The primary outcome was pain intensity measured by the Brief Pain Inventory (BPI) ,38 at wen = 28 patients . Sensory and affective pain were measured using a subscale of the Short-Form McGill Pain Questionnaire (SF-MPQ) [Pain impairment was measured by the BPI ,38. FMS-(SF-MPQ) . Somatic(SF-MPQ) . It cont(SF-MPQ) . All queg, 10 min, 4 °C) and stored at −80 °C until analyses. Plasma cytokine levels were determined by high-sensitive enzyme-linked immunosorbent assays (ELISA) with detection limits of 0.022 pg/mL for TNF-α, 0.031 pg/mL for IL-6, 0.130 pg/mL for IL-8, and 0.090 pg/mL for IL-10. Serum concentrations of CRP, ESR and WBC differential were analyzed by the local clinical laboratory.Blood samples were collected at baseline (T0), immediately after the last treatment session (T1) and at the following week  to determine systemic concentrations of key pro- and anti-inflammatory cytokines . Average daily interval of T1 and T2 blood collection was 4.16 ± 1.08 days. At these timepoints, also a routine laboratory testing with C-reactive protein (CRP), erythrocyte cell sedimentation rate (ESR) and white blood cell (WBC) differential was performed. Venous blood was collected in tubes containing EDTA  and plasma was separated by centrifugation  was reported as an effect-size estimator. A partial eta square of 0.01, 0.06, and 0.14 corresponds to a small, medium, and large effect, respectively. All results are reported as mean ± standard deviation (M ± SD). Analyses were performed using the Statistical Package for Social Sciences software .Intention-to-treat analyses were performed. Missing values were imputed 50 times using the Markov–Chain–Montecarlo-procedure. The primary outcome was evaluated using an analysis of covariance (ANCOVA) with baseline scores as covariate to control for group differences in pain intensity at baseline and with group as between-subject factor. Blood parameters were evaluated using multivariate repeated-measures analysis of variance (rmANOVA). Post hoc d = 0.60) with clinical relevance was assumed based on prior results by Brockow et al. [A moderate effect size  and analyzed  and were medically assessed for eligibility at the clinic. Finally, 41 subjects (93%) fulfilled inclusion and exclusion criteria and were randomized .The intervention group showed an average reduction in pain intensity from baseline of 1.7 points , while pain intensity in the control group was reduced by 0.5 points . In addition, a clinically relevant reduction in pain of 30% from baseline was found in 10 patients of the intervention group and in 4 patients of the control group  with an average reduction of pain intensity of 0.9 points . Pain intensity in the control group was increased by 0.5 points . Pain impairment measured at week 30 was statistically significantly different between the groups in favor of mild WBH . Mental health index score as measured with the SF-36 at week 4 showed statistically significant differences between the groups in favor of mild WBH . Secondary outcomes are presented in p-values.A statistically significant pain reduction in favor of the intervention group was found at week 30  and neutrophil counts .Analyses including all blood parameters as outcome variables revealed a statistically significant time × group interaction for lymphocyte  at T1  with a greater increase in lymphocyte count by mild WBH (p = 0.033) at T2  with higher scores in the mild WBH group (p ≤ 0.001 (B = −0.905 ± 0.257) and in the timeframe T0 to T2 with p = 0.017 (B = −0.984 ± 0.402).Post hoc mild WBH A. NeutroBH group B. Multilp = 0.027, B = −0.285 ± 0.126) on pain intensity, detecting that an increase in IL-6 concentration results in a statistically significantly less pain intensity (timeframe T0 – T1).Analyses showed no significant time × group interaction for cytokines. However, multilevel analyses revealed a negative effect of IL-6  and neutrophils  on IL-6 regarding the time course .A fixed-effects model showed statistically significant positive effects of lymphocytes  and rise in body-core temperature . There is a significant negative correlation between lymphocyte cell count (T0) and the maximum temperature reached at the first session, r = −0.510, p = 0.026, i.e., the lower the lymphocyte cell count (T0) was, the higher the body-core temperature was afterwards.A total of 18 subjects in each group, corresponding to 86% for intervention, resp. 90% for control, received the full treatment series of six interventions. Mean duration of heating-up phase in the intervention group was 45.30 ± 6.59 min (range: 35.17–57.17 min) and average plateau phase was 14.69 ± 6.64 min (range: 3.00–24.83 min). Subjects of the intervention group had a mean body-core of 38.7 ± 0.2 °C at the end of the treatment, resulting in an average rise of 1.5 ± 0.3 °C. The control group showed a highest average body-core temperature of 37.5 ± 0.3 °C, resulting in a mean rise of 0.3 ± 0.2 °C. As expected, the intervention group had a significantly higher average maximum body-core temperature . More temperature data, pulse rate, and oxygen saturation can be found in In addition, the intervention group showed a higher difference in baseline body-core temperature between the first and the sixth treatment, indicating a higher reduction in body-core temperature in mild WBH  were convinced to be part of the active condition, while 16 of 20 control patients (80%) were assuming this.In the intervention group one patient missed the second treatment due to dizziness and redness after the first session of mild WBH. Another patient experienced severe dizziness and circulatory problems during the first treatment. Therefore, she received an infusion to stabilize her general condition. Side effects did not lead to a discontinuation of the treatment series in any patient of the intervention group. One patient of the control group discontinued the treatment series after the fourth session due to fatigue. A detailed presentation of side effects during the interventions, based on the reports of the therapists, is provided in First, pain intensity 1 week and 6 months after the end of the treatment was significantly lower in the wIRA-WBH group compared to the control after the intervention series. A midterm sustained pain reduction can be achieved by wIRA-WBH. In addition, exploratory analyses revealed a reduction in pain impairment in the intervention group at week 30 and better mental health at week 4. Second, no severe adverse events were observed in either the intervention or the control group which indicates safety of mild wIRA-WBH, and tolerability was high. There were no drop outs due to side effects. Third, clinical results were supported by immunological data which showed a significantly higher increase in immune cell counts in the wIRA-WBH group. Higher blood lymphocyte numbers and IL-6 levels appeared with lower pain intensity.The observed effects on pain intensity are in line with the previous controlled trials of wIRA-WBH in FMS ,19,22, tThe generally mild side effects are in line with the previously reported studies on mild wIRA-WBH in FMS . Body-cThe mental health summary score of SF-36 questionnaire was higher in the intervention group at week 4. This is interesting as the physical part of SF-36 showed no difference between both groups. In the previous controlled trials on WBH in FMS, Romeyke and Stummer  focused Though FMS is considered a chronic syndrome rather than an inflammatory disease, it exhibits distinct systemic immunological patterns, including changes in neutrophil and lymphocyte counts and elevated levels of IL-6, IL-8, and TNF ,52. ImmuThus, pain relief could have been achieved by thermotherapy-induced immune stimulation. In addition, immunological processes are supported by the higher reduction in body-core temperature in mild WBH, and may also indicate physiological adaptation as part of the strong stimulus of the therapy. Another interesting observation is the inverse correlation of lymphocyte cell number with the maximum body-core temperature reached at first session. Further studies should examine the coherence between immune system and nervous system, and the presence of chronic pain.To our knowledge, the study is the first to investigate the effects of mild wIRA-WBH in patients with FMS in an outpatient setting. The main strength of the present trial was the establishment of an adequate sham condition with high credibility in the framework of a randomized controlled setting. Further, a priori sample size calculation ensured that the study was sufficiently powered to detect the group differences. The immunological data allow a combination of subjective and objective parameters and thus further supports the validity of the results.Even if the control condition of the present trial is considered a main strength, it should be noted that it was no traditional placebo treatment, since a small amount of the postulated key factor (heat) was applied as well. However, this was considered the only way to construct a credible control condition in heat applications and effects should be limited. Besides the monocentric setting, another limitation of the present trial was that it was not fully blinded and thus a different treatment by therapists with possible influence on results cannot be excluded. However, this is not possible due to the different treatments in the two conditions and therefore only patients who had no previous hyperthermia experience were included.Considering the wide range of possible applications of wIRA-WBH, the therapy is perceived to be a good treatment option to reduce pain in patients with FMS. Future research should investigate the effects of mild wIRA-WBH within a multicenter design.


Splanchnic nerve block is considered to be effective for abdominal visceral pain, and is performed for the purpose of controlling abdominal pain and back pain caused by upper abdominal cancer. The patients in this case report were candidates for splanchnic nerve block owing to cancer-associated pain. However, because they could not assume the prone position that is required for the block owing to their pain, combined epidural anesthesia was used, resulting in successful implementation of the splanchnic nerve block. Patients who are candidates for splanchnic nerve block often have advanced cancer, and it is hence often difficult to secure and maintain the position required for the procedure owing to their severe pain. The two patients presented here suggest the possibility that epidural anesthesia might be useful as an adjunct in such cases. The celiac plexus lies anterior to aorta at the level of the first lumber vertebra. Splanchnic nerves are paired nerves arising from the thoracic sympathetic trunk (ganglia 5–12) which pierce the crura of the diaphragm at the T11 and T12 levels to join the celiac ganglion. Splanchnic nerve block is considered to be effective for visceral pain in the upper abdomen and is performed in the prone position under computed tomography (CT) guidance. In this report, we present two cases in which the addition of epidural anesthesia facilitated the successful administration of splanchnic nerve block in patients who were considered to be suitable for the procedure owing to their cancer-associated pain, but they were unable to assume the position required for the block, owing to their pain. We obtained written informed consent from the patients to publish this case report.The first case was a woman in her sixties who was diagnosed with pancreatic cancer and had epigastric and back pains, and she was referred to our department for pain control. The prescription included a fentanyl transdermal patch (167 mcg/h), loxoprofen sodium hydrate (180 mg/day), and oxycodone hydrochloride hydrate (45 mg/day). The patient reported symptoms of stabbing pain in the epigastric region and dull pain in the back, and sometimes complained of unbearable pain. She had no appetite and also had sleep disturbances. She had a numerical rating scale (NRS) score of 10/10 for pain, a Self-Rating Depression Scale (SDS) score of 43/80, a Kessler Psychological Distress Scale (K6) score of 23/24, and an EuroQol 5 Dimension (EQ-5D) score of 0.594. Abdominal CT showed a tumor of ∼36 mm in the body of the pancreas, with possible infiltration into the splenic artery, celiac artery, and portal vein . After cThe second case occurred in a woman in her fifties with pancreatic cancer. She complained of severe pain in the epigastric and back regions, and she was referred to our department for pain control. She was taking oxycodone hydrochloride hydrate (30 mg/day) and loxoprofen sodium hydrate (189 mg/day). She had no appetite, but did not have any sleep disturbances. Her NRS was 6/10, SDS was 45/80, K6 was 3/24, and EQ-5D was 0.228. Abdominal CT showed a tumor of about 27 mm in the pancreatic head, and multiple metastases were observed in the liver . The day1–3 The patients of both cases presented in this report had poor pain control with opioids and experienced visceral pain owing to pancreatic cancer. Therefore, splanchnic nerve block was felt indicated for both patients. In general, when performing a splanchnic nerve block, the patient is placed in the prone position5  block. A TAP block is generally considered to provide somatic analgesia, but without any effect on visceral pain. Importantly, there have been several reports that TAP blocks were effective in treating visceral pain.Based on the findings of the two cases presented in this report, the combined use of epidural anesthesia can be considered to be helpful in managing the difficulties associated with patients maintaining the prone position during splanchnic nerve block. However, precautions should be taken to prevent complications, such as hypotension during administration of epidural/spinal anesthesia.


Opioid-free anesthesia (OFA) is an alternative to conventional opioid-based anesthesia (OBA) in patients undergoing bariatric surgery. Several small studies and a meta-analysis have suggested advantages of OFA for bariatric surgery, but current evidence is still contradictory, and a universally accepted concept has not yet been established. The purpose of this study was to determine whether patients undergoing bariatric surgery experience less postoperative pain and better postoperative recovery when anesthetized with an OFA regimen than with an OBA regimen.This prospective observational cohort study, conducted between October 2020 and July 2021, compared patients receiving OFA with patients receiving OBA. Patients were visited 24 and 48 h after the surgical procedure and asked about their postoperative pain using the visual analogue scale (VAS). Additionally, the quality of recovery-40 questionnaire (QoR-40) and the postoperative opioid requirements were recorded.N = 50; OBA: N = 49). The OFA cohort exhibited less postoperative pain than the OBA cohort within 24 h (VAS median [interquartile range (IQR)]: 2.2 [1–4.4] vs. 4.1 [2–6.5]; P ≤ 0.001) and 48 h  postoperatively. Additionally, the OFA cohort had higher QoR-40 scores and required less opioid therapy postoperatively.Ninety-nine patients were included and analyzed in this study (OFA: Based on our results the use of OFA for bariatric surgery results in less pain, reduced opioid requirements, and improved postoperative recovery—adding additional evidence regarding the use of OFA in everyday clinical practice.The online version contains supplementary material available at 10.1007/s11695-023-06584-5. Opioid-free anesthesia (OFA) has been used for several years in an attempt to reduce risks and to improve recovery after surgery by decreasing opioid-induced side effects. For OFA, opioids are replaced by anesthetic adjuncts, such as ketamine, lidocaine, dexmedetomidine, and magnesium –5. The uPatients receiving bariatric surgery have a high risk for PONV , 17 and At our center, an OFA regimen has been used in parallel with an opioid-based regime (OBA) in bariatric surgery since June 2018. This study aimed to investigate the effects of these concepts on postoperative pain and recovery after a period of 48 h in patients who underwent bariatric surgery in everyday clinical practice.This prospective single-center cohort study examined postoperative pain, perioperative opioid consumption, PONV and the quality of recovery in patients undergoing first-intervention bariatric surgery between October 2020 and July 2021 at the Medical University of Vienna, Austria. We compared patients receiving OFA with patients receiving OBA. Informed consent was obtained from all individual participants included in the study. The study was approved by the Ethics Committee of the Medical University of Vienna (EK 1748/2020) and was performed in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki.2 undergoing first-time bariatric surgery under general anesthesia were included. Patient age was restricted to 18–65 years, and written informed consent was required before inclusion. Only patients who could be interviewed postoperatively were included. If a postoperative survey was not possible (e.g. study team was unavailable or language barrier), the patient was not included. Patients for whom the anesthetic regimen was changed intraoperatively (from OFA to OBA or vice versa) were excluded. When the sample size was reached in one cohort, no more patients were included in this cohort.The operating room schedule was regularly screened for eligible study participants, and eligible patients were contacted. Patients with a body mass index (BMI) greater than 35 kg/mPatients were assigned to respective cohorts according to the type of anesthesia (OFA/OBA) performed.The form of anesthesia (OFA/OBA) used was chosen by the anesthetist in charge and was determined on the basis of the standard operating procedure (SOP) of the respective operating room of the respective area. In our center, there are two sections of operating rooms performing bariatric surgery. In section 1, mainly OFA is applied, in section 2 OBA. Whether a patient is assigned to section 1 or 2 is random. To provide data from everyday clinical practice without a controlled trial setting, the study team had no influence on the treatment overall or choice of anesthesia at any time. OFA was performed according to an SOP. For anesthesia induction, a continuous intravenous infusion of s-ketamine (1.25 mg/ml), dexmedetomidine (10 µg/ml), and lidocaine (10 mg/ml) was started at 20 ml/h . Then, 200–250 mg propofol and 100 mg rocuronium were administered.For maintenance, depending on the individual requirements of the patient, the syringe pump was set at 5 to 10 ml/h , and a volatile anesthetic (sevoflurane/desflurane) was administered. In addition, metamizole (2.5 g), magnesium sulfate (2–4 g), and parecoxib (40 mg) or diclofenac (75 mg) were administered intraoperatively. In the recovery room, continuous infusion could be continued at 5 ml/h as first-line analgesic therapy. Piritramide was available as a rescue therapy. This SOP is a modification of Mulier’s OFA protocol  VAS in the first 24 h postoperatively was 2.2 [1–4.4] in the OFA cohort and 4.1 [2–6.5] in the OBA cohort . 26 (52%) of 50 patients in the OFA group and 38 (77.6%) of 49 patients in the OBA group received droperidol in the PACU .Numeric secondary outcome parameters are shown in Table P ≤ 0.001) and 48 h (OFA: 183 (9.7), OBA: 173 (11.6); ≤ 0.001) in favor of the OFA group. The differences in QoR-40 regarding postoperative pain are shown in Table P = 0,609). In the OFA cohort, 15 (30%) patients were discharged between 24 and 48 h after surgery, and 12 (24%) patients were discharged between 24 and 48 h in the OBA cohort .We found statistically significant differences regarding QoR-40 scores after 24 h (OFA: 166 13.5), OBA: 155 (16.5); .5, OBA: The use of opiate-free anesthesia is reported to be associated with less postoperative pain and better postoperative recovery in bariatric surgery, but there is no universally accepted concept yet, and some aspects have not been adequately investigated. In this prospective cohort study comparing an OFA regimen with an OBA regimen in patients undergoing bariatric surgery, patients were surveyed 24 and 48 h postoperatively regarding their postoperative pain, as well as their postoperative recovery, to investigate whether the results found in a controlled trial setting can be confirmed in everyday clinical practice. Our hypothesis was that the results found in controlled trials, could be transferred to everyday clinical practice without a controlled trial setting and that, accordingly, patients receiving OFA would have less postoperative pain and better postoperative recovery. We observed statistically significant differences in postoperative pain and postoperative recovery between the cohorts over a period of 48 h postoperatively. Patients in the OFA cohort had significantly lower pain scores, lower opioid requirements, and recovered faster than patients in the OBA cohort.Given that patients undergoing bariatric surgery have high rates of PONV , 17 and We could show a statistically significant difference regarding PONV within 24 h postoperatively in favor of the OFA group. These findings are in line with the results of previous investigations , 14 and We assumed, from clinical experience and due to the fact that these parameters are included in the QoR-40, that the differences found in the QoR-40 were related to the outcome parameters of postoperative pain, PONV, and postoperative opioid consumption. This would also correspond to the findings presented in Table According to a retrospective study by Mulier et al., OFA improves the outcome of bariatric procedures; thus, this regimen can be assumed to be safe for use in this patient population . Our stuWe found no difference regarding LOS, even though the patients in the OFA group showed statistically significant differences in the QoR-40 questionnaire 24 and 48 h postoperatively. These findings contradict the results of a comprehensive retrospective analysis of a large patient collective done by Mulier et al. . HoweverA limitation of this study is that it was conducted at a single center, limiting the generalizability of our results. Due to the size of our department (approximately 180 anesthetists), we nevertheless believe that these methods can be applied by a large variety of anesthetists.The results of this study showed that the introduction of a concept for OFA in clinical routine practice was associated with less postoperative pain, lower opioid requirements and less PONV and patients demonstrated improved postoperative recovery. Further studies are needed to determine the best anesthetic protocol and to investigate safety aspects with this form of anesthesia.Supplementary file1 (PDF 106 KB)Supplementary file2 (PDF 121 KB)Below is the link to the electronic supplementary material.


The mean duration of the effect of BoNT/A on pain was 95.00 ± 53.03 days and no adverse effects were reported.Auriculotemporal neuralgia is a rare pain disorder in which anesthetic nerve blockade is usually effective but not always resolutive. Botulinum toxin type A has proven to be effective in treating neuropathic pain, and patients with auriculotemporal neuralgia could also benefit from this treatment. We described nine patients with auriculotemporal neuralgia treated with botulinum toxin type A in the territory of auriculotemporal nerve innervation. We compared the basal NRS and Penn facial pain scale scores with those obtained 1 month after BoNT/A injections. Both Penn facial pain scale (96.67 ± 24.61 vs. 45.11 ± 36.70,  It continues upward, beneath the parotid gland, adjacent to the superficial temporal artery, and between the ear and the condyle of the mandible. It continues, beyond the parotid gland, over the zygomatic arch, and in front of the temporomandibular joint (TMJ). The auriculotemporal nerve (ATn) then pierces the temporalis muscle and divides into five branches: nerve to the external auditory meatus (innervating the tragus as well), anterior auricular nerve (which innervates the anterior part of the auricle), parotid branches, articular branches (innervating the posterior aspect of the TMJ), and the superficial temporal nerve  [zygomaticotemporal nerve, the lesser occipital nerve, and/or the greater occipital nerve [middle meningeal artery plexus and lesser petrosal nerve to the parotid gland.The auriculotemporal nerve (ATn) arises from the posterior division of the mandibular nerve, passes through the  region) ,2,3. Des region) . The aur region) ,6. Thereal nerve ,7,8. TheBased on its anatomical distribution, pain arising from this branch may also be perceived in the temporal region, TMJ, in the parotid, retro-auricular and retro-orbital region. Auriculotemporal neuralgia (ATN) is a rare facial pain disorder involving the auriculotemporal nerve (ATn) characterized by unilateral and side-locked pain localized in the temporal scalp, auricular region, temporomandibular joint, and/or parotid region. It is a rare and unusual facial pain disorder that occurs with a frequency of 0.4% in tertiary headache outpatient clinics . The paipterygoideus externus muscle due to muscle spasm or inflammation, the wrapping around the superficial temporal artery, or the compression at the level of fascia bands in the preauricular area, were proposed to be possible causes of the issue [pterygoideus externus and pterygoideus internus muscles [The quality of pain is frequently throbbing, possibly due to the proximity to the temporal artery, but could also be lancinating, stabbing, or shock-like, and the intensity is moderate to severe. The symptoms could be triggered by chewing, talking, jaw traumas, gustatory stimuli, facial tactile stimuli, or pressure over the preauricular region. Tenderness and allodynia over the preauricular region are frequent features . The enthe issue ,13,14. T muscles ; moreove muscles . Other f muscles ,17. The  muscles ,10, howeDamarjian performed from one to fourteen local anesthetic nerve blockades in ATN patients describing a recurrence rate of 30% after 1–2 years . CarbamaThe literature is scarce with regard to the therapy of refractory cases, but a recent article reported one case of successfully treated refractory ATN with botulinum toxin type A (BoNT/A) . BotulinAltogether, data from nine patients were collected . The mean duration of the ATN was 10.38 ± 12.21 months. The pain was unilateral in all cases (six left-sided and three right-sided) and it was localized in the ATn innervation region. Radiating pain frequently involved the retro-orbital, occipital, or mandibular region; patients three and four referred infrequent ipsilateral cervical and/or neck radiating pain. Pressure over the temporal fossa and preauricular area caused pain exacerbation in all the patients; seven out of nine had allodynia in the ipsilateral temporal region, while one had hypoesthesia (patient 7). Seven patients had dull background pain in the territory of the auriculotemporal nerve with daily paroxysmal exacerbations, while two had paroxysmal pain only. The pain was mainly described as stabbing, throbbing, or shock-like; however, one patient described the pain as burning. Six patients were on medications for pain although with minimal or no benefit. Anesthetic nerve blockade of the auriculotemporal nerve with 1–2 mL of 0.5% bupivacaine determined complete pain relief almost immediately, but only for a short period (from 1 day to 10 days). See p 0.004; mean reduction 52.57 ± 36.50) and NRS scores  improved significantly at one month after treatment. The mean duration of the effect of BoNT/A on pain was 95.00 ± 53.03 days. No adverse effects were observed or reported.The ATn anesthetic nerve blockade was repeated seven times in patient 9 and five times in patient 8; the other patients were treated two times before BoNT/A therapy. Each procedure was able to abolish pain in every patient and the effect had a similar duration; the interval time between one anesthetic block and another was one week. No adverse effects were reported after this procedure. In our cohort, the mean dose of BoNT/A was 60.56 ± 19.44 U. The effect of BoNT/A started 7–10 days after the injections. Three patients  had a prolonged response (5–6 months duration) with complete pain relief occurring 3 months after the treatment; four patients  showed partial pain relief which lasted for 3 months, while the last two patients (patients 7 and 8) had only a poor response with a short duration (30–45 days). Detailed results are summarized in p 0.036), mood (p 0.035), normal work (p 0.022), relationship with other people (p 0.022), sleep (p 0.014), enjoyment of life (p 0.008), and touching the face (p 0.035). There was also a reduction of the “worst pain” (p 0.009), “least pain” (p 0.034), “average pain” (p 0.034), and “pain right now” (p 0.022) items  showed that BoNT/A treatment significantly reduced the interference of ATN pain in general activity (2) items .The differential diagnosis mainly arises with temporomandibular disorders (TMD), migraine, continuous hemicrania, otitis, affection of the parotid gland, temporal arteritis, odontalgia, nummular headache, atypical facial pain, and trigeminal neuralgia (TN). TN is characterized by recurrent attacks of lancinating or stabbing pain in the dermatomal distribution of the trigeminal nerve, sometimes associated with a continuous background facial pain; the pain usually affects the V2 and V3 distributions while only less than 5% of patients suffer from pain in the V1 distribution. Autonomic symptoms such as conjunctival injection or tearing, miosis, ptosis, sweating, and clogged nose can occur with trigeminal neuralgia on the same side as the pain. The most frequent triggers in TN are mastication, brushing teeth, speaking, touching the site of pain, and cold wind exposure. Antiseizure drugs and tricyclic antidepressants are effective treatments, in particular carbamazepine, which is the first-line therapy for TN. In refractory cases, surgical treatment such as microvascular decompression, radiofrequency, or thermocoagulation can be performed . AlternaIn our tertiary care center, referring from a large area, the prevalence of ATN among headache patients in our outpatient clinic was 0.23% and the mean age of onset was 48.22 ± 13.01 years, in accordance with the previous literature ,10,11. ABoNT/A could be a safe and effective alternative treatment in cases of auriculotemporal neuralgia. Further studies, specifically placebo-controlled studies, are needed to confirm the efficacy and safety of this procedure in the treatment of ATN.This is a retrospective longitudinal single-center study. We retrospectively collected the data from 9 patients affected by ATN seen in our tertiary headache outpatient clinic from January 2017 to September 2022. Before the diagnosis of ATN, every patient performed an extensive neurological examination, neuroimaging (brain and TMJ MRI or CT), and blood work-up to exclude secondary causes. Temporo-mandibular joint function and mobility and peripheral cranial nerve tenderness were evaluated. Diagnosis of ATN was performed according to the criteria suggested by Ruiz et al. .®) using a 30-gauge 0.30 × 8 mm needle. When performing the subcutaneous injections, we grasped the area of the skin surrounding the injection site to separate it from the muscular layer and then we thrust the needle with an injection angle of 30–45° into the subcutaneous tissue  , numerict-test, when the data had normal distribution, or a Wilcoxon test when the distribution of the data was not normal. A Shapiro–Wilk test was used to assess the normal distribution of data. All analyses were conducted using Stata/SE  for Mac OS. Statistical significance levels were set at p < 0.05.A descriptive analysis of the study population’s continuous variables was performed using mean ± standard deviation (SD). For the comparison of PFPS and NRS between baseline and 1 month after BoNT/A injections, we utilized a paired