ObjectiveDelivery of a robust local anesthetic injection aids in the successful management of all patients' fears, anxieties, and discomfort during dental treatments. The most expected or frightening stimuli in the dental operatory are local anesthetic injections. The objective of this trial was to study the analgesic efficacy of distant cold stimulation in relieving injection pain from the greater palatine nerve block. Before receiving local anesthetic injections, employing cryotherapy by using an ice bath changes the pain perceptions and also increases the pain threshold.PurposeThe aim of this study is to evaluate the effect of distant cold stimulation on palatal injection pain using an ice-cold bath.MethodThis was a randomized, controlled trial conducted at an oral and maxillofacial surgery department. A split-mouth technique was employed for the study, in which patients requiring bilateral greater palatine nerve block for any dental procedures were included. The bilateral greater palatine nerve block was given one at a time, separated by an interval of three days. The inclusion criteria for this study were no history of drug allergy and an extraction site free of any active infection. There were 28 participants in this experimental study. Two groups were randomly created from this research sample: group A  and group B . In group A, the patient was asked to put his or her hand of the same side as the palatal injection in an ice-cold bath till the time patient could tolerate it; immediately after the patient removed his hand, the greater palatine nerve block was given, and the patient was assessed for the injection pain. In group B, the patient was directly given the greater palatine nerve block without any distant cold stimulation. The time interval between the two extractions/dental procedures was three days. Outcomes of interest were pain severity with and without distant cold stimulation which were assessed using a Visual Analogue Scale (VAS) pain scale, and a comparison was made between the two groups.ResultsAs per our study, in terms of pain, there was a statistically significant difference between the two interventions at all time points. Patients in group A had a lower score on the VAS pain scale as compared to group B. The standard deviation (STD) for group A was 0.81, and the standard deviation for group B was 0.92. P value was derived to be P < 0.001, which is suggestive of a significant difference between the pain scores of both groups.ConclusionHence, we conclude that the use of distant cryotherapy as an adjunct is an effective way to reduce pain perception and increase pain threshold. This technique is comparatively simple, painless, and easy for the surgeon and for apprehensive patients, and it offers a fair cost solution for the suffering often associated with dental procedures requiring local anesthetic injections. Local anesthetic injection to the palate in addition to buccal anesthesia is commonly used for dental treatments involving the maxillary posterior teeth. A dental phobia that lasts for an average of about 24 years might develop as a result of the terribly distressing experience that many patients have with palatal injections . In thisTo lessen the discomfort experienced during the administration of local anesthetic agents, especially during the palatal injection, researchers have employed a variety of desensitization techniques, including the use of topical anesthetics, warming and buffering of the anesthetic solution, counter-irritation, vibration or pressure, acupuncture, hypnosis, and computer-controlled delivery systems (WAND), utilizing several equipment such as dental vibe, vibrajects, or jet injectors to reduce discomfort experienced during the local anesthetic injection -9.Another recommended method that has been shown to be efficient and cost-effective is the use of cryotherapy. In order to reduce discomfort from the injection site, ice is applied at another site; this alters the nerve conduction velocity . The useThis study was undertaken for a comparative evaluation of the patient’s perceived pain response to the greater palatine nerve block which was given after exposure of the patient’s hand to an ice-cold bath for two minutes. This pain perception was assessed using a Heft-Parker Visual Analog Scale.Study designThis was a single-center, prospective, randomized clinical trial comparing the local anesthetic injection pain with and without distant cold stimulation. The study was approved by our institutional review board and institutional ethics committee prior to inception. Informed written consent was obtained from all patients before carrying out the procedure.Study setting and populationThis study was conducted in an oral and maxillofacial surgery department. A convenience sample of 28 patients was identified by trained research assistants who received a briefing on the study criteria and objectives. These patients required bilateral extraction of teeth from the maxillary first premolar to the maxillary third molar. The subjects were selected keeping in mind the following inclusion criteria such as no history of drug allergy and extraction site free of any active infection. Patients were excluded from the study if they had a contraindication to the local anesthetic injection or had any prior allergy, medication intolerance, or history of peptic ulcer disease. This study was conducted by a split-mouth technique, wherein extractions were done one at a time separated by a gap of at least three days.Study protocol and methodologyThe collection of demographic and clinical data was done using a standardized data collection form. Data collected included demographic information such as the age and sex of the patient. Patients were given an information sheet and were explained in detail regarding the procedure and study. Written informed consent was taken from the patient before the procedure for publication of the study findings. A detailed case history was obtained from all the patients participating in the study, and standard sterilization protocol was followed throughout the study. All the patients were explained about the visual analog performa pre-operatively, which was filled by the patients based on their experience post local anesthetic injection. All injections and extractions were performed by the same surgeon, and all the parameters were recorded by the same clinician. Treatment assignments were enclosed in sequentially numbered, opaque, and sealed envelopes. The envelopes contained even proportions of the two study treatments. For each enrolled patient, the next in the series of envelopes was opened to reveal the treatment allocation.Painting and draping were done under an aseptic protocol. An ice-cold bath was prepared by taking ice cubes in a steel tray. In the first appointment, the patient was asked to put his or her hand of the same side as the greater palatine nerve block injection in this ice-cold bath till the time patient could tolerate it Figure . This waImmediately after the patient removed his hand, the greater palatine nerve block was given using 2% lignocaine with adrenaline and the patient was assessed for injection pain after the distant cold stimulation. The pain was evaluated immediately after the local anesthetic injection was given, using a 10-point Heft-Parker visual analog scale (VAS) marked by the patient herself or himself based on the pain experienced by the patient. Following this, a routine extraction procedure was carried out.For the extraction of the other side, the patient was directly given the greater palatine nerve block using 2% lignocaine with adrenaline, without any distant cold stimulation. Immediately following the local anesthetic injection, the patient was asked to mark the pain experienced during the injection on a 10-point visual analog scale. The time interval between the two extractions was three days. Due to the nature of the intervention, it was not possible to blind the patient and physician to the treatment allocation.Heft-Parker Visual Analogue ScaleIt is a subjective method used to measure chronic and acute pain. It is a 10-pointer numeric rating scale on which patients rate their current pain intensity, ranging from “0” (no pain) to “10” (worst possible pain). These scores were recorded for all the patients and were then forwarded to the statistician for statistical analysis. All the patients were given post-operative instructions and medications following the extractions for three days. The patient was recalled after three days for the extraction in the opposite quadrant.Outcome and measurementsThe main outcome measure was the difference in pain severity score on a 10-point VAS pain scale with and without distant cold stimulation. VAS was marked by the patient immediately after the local anesthetic injection. The patient’s data were statistically analyzed using a software named IBM SPSS Statistics 20.0 . All the statistical data were compiled in a tabulated and graphical format.Descriptive and inferential statistical analyses were carried out in the present study. Results on continuous measurements were presented on mean + SD. The level of significance was fixed at P = 0.05, and any value less than or equal to 0.05 was considered to be statistically significant. Student t-tests  were used to find the significance of study parameters on a continuous scale between the two groups. The standard deviation for group A (with distant cold stimulation) was derived to be 0.81 and for group B (without distant cold stimulation) was derived to be 0.92 Tables . Here, tThe statistical software IBM SPSS Statistics 20.0  was used for the analyses of the data, and Microsoft Word and Excel  were used to generate graphs, tables, etc.Dental fear and needle phobia are the two biggest difficulties that a dentist faces in day-to-day life. Local anesthetic injections are an imperative part of all surgical procedures and dental extractions . The sysThe "gate control theory of pain" may assist in comprehending the mechanism behind the analgesic action of cryotherapy. Cryotherapy when used, it acts as a defense against anesthetic injection. It reaches the brain before the pain experience does since the brain can only acknowledge one sensation at a time. Cryotherapy, a form of counterstimulation, thereby lessens pain perception. Although if the impact of cryotherapy lasts just a short while, it is sufficient to lessen the pain brought on by the insertion of an anesthetic needle . CryotheMany clinical studies have been carried out to evaluate the efficacy of cryotherapy in increasing the pain threshold. A clinical trial by Aminah et al. examined the effects of various desensitizing techniques on reducing injection pain in children, including local anesthetic gel, pre-cooling the injection site, vibration, and buffering the anesthetic solution, and came to the conclusion that cryotherapy significantly decreased the pain perception in children . SimilarThe purpose of the current study was to evaluate the effect of cryotherapy on perceptions of pain. This study has taken into account the palatal injection, which is thought to be more painful than other injections in the oral cavity. To avoid bias and take into account that each patient experiences pain differently, patients who needed bilateral greater palatine nerve block for any of the dental procedures were enrolled in this split-mouth study. The amount of pain experienced by the patient was recorded using a visual analog scale (VAS). The patient was instructed to place the hand of the same side as the palatal injection in an ice-cold bath for as long as they could tolerate it during their first appointment. As soon as they took their hand out, a greater palatine nerve block was administered, and the patient's tolerance for the injection pain was evaluated. The greater palatine nerve block was administered to the patient without any cold stimulation in preparation for the extraction of the opposite side. Three days passed in between the two extractions. The findings of this study confirm the hypothesis that cryotherapy greatly reduces pain at the time of needle penetration during local anesthetic administration for dental treatment. As compared to the control group, the scores on the VAS pain scale were lower in the cryotherapy group.The outcomes of this study are consistent with the research done by Harbert, who used cold to reduce the pain perception associated with palatal injections . This stBased on the results of this research, in terms of pain, there was a statistically significant difference between the two interventions at all time points which means that the pain scores in group A (with distant cold stimulation) were much less as compared to the pain score in group B (without cold stimulation). To conclude, cryotherapy administration prior to local anesthetic injection may be recommended as a simple and affordable auxiliary approach that is advantageous to all patients with fear and anxiety. It also lowers pain perception by acting as a defense against injection pain. It reaches the brain before the pain experience does since the brain can only acknowledge one sensation at a time. It raises the pain threshold via parasympathetic stimulation. It provides a reasonably priced remedy for the agony usually connected with dental procedures.


A series of epidemiological studies have shown the limited life expectancy of patients suffering from idiopathic normal pressure hydrocephalus (iNPH). In most cases, comorbid medical conditions are the cause of death, rather than iNPH. Though it has also been shown that shunting improves both life quality and lifetime. We sought to investigate the utility of the Charlson comorbidity index (CCI) for improved preoperative risk–benefit assessment of shunt surgery in individual iNPH cases. 208 shunted iNPH cases were prospectively investigated. Two in-person follow up visits at 3 and 12 months assessed postoperative clinical status. The correlation of the age adjusted CCI with survival was investigated over the median observation time of 2.37 years (IQR 1.16–4.15). Kaplan Meier statistics revealed that patients with a CCI score of 0–5 have a 5-year survival rate of 87%, compared to only 55% in patients with CCI > 5. Cox multivariate statistics revealed that the CCI was an independent predictor of survival, while common preoperative iNPH scores , gait score, and continence score) are not. As expected, mRS, gait, and continence scores improved during the postoperative follow up period, though relative improvement on any of these was not predicted by baseline CCI. The CCI is an easily applicable preoperative predictor of survival time in shunted iNPH patients. The lack of a correlation between the CCI and functional outcome means that even patients with multiple comorbidities and limited remaining lifetime may appreciate benefit from shunt surgery. While recent epidemiological and clinical studies have shown the limited life expectancy of iNPH patients6, it has also been reported that shunting may improve the life expectancy4, and furthermore this beneficial effect may be diminished in iNPH patients who are not treated by shunting in a timely manner7.Idiopathic normal pressure hydrocephalus (iNPH) is a disease of the elderly, and it is well established that iNPH patients can clinically benefit from shunt surgery8. A large epidemiological registry study revealed that iNPH itself was coded as underlying cause of death in less than 5% of iNPH patients4. In the preoperative setting, comorbidities can be quantitatively assessed in individual patients by applying the Charlson comorbidity index (CCI)9, and the age-adjusted CCI allows for the long-term survival prediction10. Accordingly, the CCI comprises a useful tool for weighing the potential benefits versus harms of a medical or surgical treatment during the remaining lifespan11. While the CCI has been validated to provide such useful information on the remaining lifetime in numerous diseases, it has not yet been validated for this purpose in iNPH12.Comorbid medical conditions have been recognized as the cause of death in most fatal iNPH cases13. Taking a quantitative approach to this issue, we applied the age-adjusted CCI in a cohort of 208 shunted iNPH patients. Our results demonstrate that the CCI was significantly predictive of survival time in this population. Though it was not predictive of the functional outcome of shunt surgery for iNPH.At this point, because shunting for iNPH must be considered as elective surgery, neurosurgeons often face a difficult decision making for shunting in individual patients with a variety of comorbidities. Currently, it is not possible to reliably predict the survival or functional outcome of individual patients in light of preoperative comorbidity burden14. A subset of patients with equivocal radiographic or clinical findings underwent an additional high-volume lumbar tap test, though a negative tap test was not considered a strict exclusion from shunting15.A single-surgeon consecutive cohort of 208 iNPH cases who were shunted from 2015 to 2021 was prospectively studied. All patients fulfilled the diagnostic criteria of iNPH as diagnosed by clinical examination and MRI14. Those tests were also applied at the 3- and 12-months follow-up visits. In addition, based on clinician and patient reported data, clinically significant impairment of cognition was documented in a binary fashion at the preoperative visit and its improvement at the two follow up visits. Comorbidity burden was assessed at the preoperative visit applying the 19-item CCI version12, which was age adjusted , iNPH gait score, and iNPH continence score Table 1,2,13,14Patient survival time was assessed in October 2022 using a combination of the hospital’s electronic medical records and web-based obituary searches. All cases in whom death or survival could not be confirmed were censored at the date of the last clinical visit. A total of 41 deaths were confirmed.This study was IRB approved  and patients’ informed consent was waived . All methods were performed in accordance with the relevant guidelines and regulations.Availability of data and materials: Raw data are available upon reasonable request to the corresponding author.For survival time analysis, univariate and multivariate cox proportional hazards regression, and Kaplan Meier analysis with log rank testing, were performed. For evaluation of the clinical follow-up the Friedman rank sum test with post-hoc pairwise Wilcoxon rank sum test with Bonferroni correction were applied. Generalized linear modeling (GLM) was applied to assess whether the CCI is predictive for clinical outcome. All statistical analyses were completed using R software v4.2.1.The median age was 75 years (IQR 71–80). 208 iNPH cases were treated either by a ventriculoperitoneal (n = 205) or by a ventriculopleural shunt (n = 3). 98 cases (47%) were female.The median observation time for the survival statistics was 2.37 years IQR 1.16–4.15). 93% of cases (n = 194) at the 3-month follow-up, and 73% (n = 152) at the 12-month follow-up, were seen in person in our outpatient clinic. Considering that at the 12-month visit already 12 patients were deceased, the overall 12-month follow-up rate was 79%. The clinical scoring scales are shown in Table .16–4.15.The age adjusted CCI scale and the prevalence of underlying pathologies of the study group are shown in Table At the preoperative visit the median (IQR) CCI was 6 (5–8), gait score was 4 (4–6), continence score was 3 (2–4) and mRS was 2 (2–3). Cognitive impairment was reported in 184 of 208 patients (88%).Kaplan Meier survival analysis was performed applying the preoperative score findings including age-adjusted CCI, mRS, gait and continence scores Fig. .Figure 14. The CCI was dichotomized at a score of 5. That score was chosen considering the median age of the cases (70–80 years = 3 CCI points), and the high prevalence of cognitive impairment which was coded as dementia (1 CCI point). Assuming another minor comorbidity (1 CCI point), a total score of CCI ≤ 5 is characteristic of relatively healthy patients, compared to patients characterized by higher preoperative comorbidity burden (CCI > 5). Kaplan Meier statistics revealed that patients with a CCI score of 0–5 have a 5-year survival rate of 87%, compared to only 55% in patients with CCI > 5.For the Kaplan–Meier curves, preoperative results were used and the ordinal symptom scales were dichotomized for better visualization as has been reported by others: mRS score 0–2 versus 3–5 , gait score 1–4 versus 5–8, and continence score 1–3 versus 4–6p < 0.05). Of these, only the CCI remained significantly correlated with survival time on multivariate Cox regression analysis , but not for mRS or continence score.Statistical analysis applying the Friedman test revealed significant postoperative improvements in terms of all three clinical scores. The paired post-hoc Wilcoxon test revealed the improvements in all scores between the preoperative and 3-month visits, and between the preoperative and 12-month visits, to be statistically significant Table . ImproveCompared to 88% of patients with cognitive impairment preoperatively, only 81 of 194 patients (42%) remained impaired at 3-month follow-up, and only 64 of 152 (42%) cases at the 12 month follow-up.2 = 0.06). At the 12-month visit, CCI was not related to improvement of any of the clinical scores , age-adjusted CCI was statistically correlated with improvement of the mRS score at the 3-month visit, though the statistical analysis indicates higher CCI scores with improvement of the mRS and the regression coefficient is quite low  for death was significantly increased 3. In shunted iNPH, the hazard ratio is improved to 3.36. Also, it has been shown that delayed shunting of diagnosed iNPH further reduces life expectancy7. Cumulatively, these data support the notion that mortality is increased in iNPH as compared with the general population. Our survival data are consistent with these previously published data.It is a rather novel understanding that the life expectancy in iNPH is quite limited. Early reports were based on small clinical case series18. While some other studies have tried to correlate specific comorbidities, especially cerebrovascular disorders, to the onset of iNPH, the etiological relationship between iNPH and other underlying disease processes remains inconclusive. Preexisting factors like obesity, diabetes, hypertension, and others appear to have some an impact19. However, it appears that at this point it is premature to draw any conclusions and we believe that further research is needed in these areas.Importantly, while acknowledging the mortality risk in iNPH patients, previous studies have also recognized that iNPH is not a deadly disease by itself. Among 979 treated INPH cases from the Swedish Hydrocephalus Quality Registry, iNPH was coded as cause of death in only 5% of the fatal cases, implicating comorbidity burden instead as a frequent cause. Observations from other studies have also supported this notion9. Since its inception, CCI has been used in numerous studies investigating the remaining life expectancy following treatment of a variety of diseases12. The index was age-adjusted in 1994 by adding 1 score point for each decade above an age of 50 years. It was shown that the inclusion of age is important in time series studies which extend the observation time to more than a few months10. Therefore, we used the age-adjusted CCI score for our study of iNPH patients over a follow-up period of years. Until today several modifications of the original score were published; for example the score has been adjusted to ICD and other coding requirements12.First introduced in 1987, the CCI includes of a total of 19 disease conditions weighted according to relative impact on mortality12. Our results indicate that the Charlson comorbidity index can categorize individual iNPH patients in terms of life expectancy to a statistically significant extent. We demonstrate that an age-adjusted CCI score of > 5 identifies iNPH patients with a much more limited life expectancy than those with a score between ≤ 5. Our data indicate that iNPH cases with a maximum CCI score of 5 survive one year with a probability of 95%, and 5 years with a probability of 87%. Those numbers drop in cases with a CCI score of 6 and higher to 90% and 54% respectively.The Charlson index is a unique measure of comorbidity burden, since it can be easily computed by means of a questionnaire, including by patients themselvesImportantly, multivariate Cox analysis revealed that, while the CCI is an independent predictor of survival in shunted iNPH patients, comorbidity burden does not predict functional improvement as assessed by mRS, gait and continence scores.16. However, that lack of a correlation between CCI and functional improvement means that a patient with a CCI score higher than 5 may very well benefit from shunting for the remaining lifetime, information that may be helpful to providers and patients alike when weighing the risks and potential benefits of shunting.Neurological outcome in the study cohort was significantly improved comparing the preoperative visit with the 3 and 12 months follow up visits. The improvement was statistically significant with each of the functional outcome scores . This is in line with existing literature, including overall lack of further improvement from 3-month to 12-month outcome. Importantly, applying generalized linear modeling, we found no correlation between the CCI (dependent variable) and the degree of improvement in mRS, gait and continence scores (independent variables). These findings confirmed previous observations of others20. As compared to the Swedish epidemiological studies which have access to the “national cause of death registry”, we relied on documented death records in electronic medical records of the hospital and online obituaries. Because all patients with unknown survival status were censored at the last documented clinical visit , our survival analysis did probably miss a limited number of deceased cases. However, the survival rate could be calculated within reasonable 95% confidence intervals up to seven years follow up. Finally, there exists the issue that the CCI may overestimate life expectancy because it was assessed only once prior to shunt surgery, not accounting for potential increases in patient comorbidity burden during the follow up period. This issue is currently under investigation11, and meanwhile cannot be addressed with routine statistical procedures.Data of this prospective study were collected at the preoperative and the two follow up visits. Our population’s mRS scores ranged from 1 to 4, with no scores of 5 (bedridden) at the preoperative or follow up visits. This likely reflects referral trends, such that mRS = 5 cases were not referred to our outpatient clinic because they were not considered as candidate for invasive treatment procedures. Our overall loss to follow-up rate is similar to other iNPH studies, though the validity of our results is affected especially at the second follow-up visitEventually, those limitations indicate the need for future studies which should address specific issues, including: a more detailed examination of neurodegenerative comorbidities not included within the CCI but which may influence survival and further analysis of how comorbidities influence mRS and the gait scale. While not presented in the current analysis, future analyses might also employ improved collection of morbidity data to enable a more precise calculation of survival time with respect to each incremental point-wise increase in CCI. Finally, as practice potentially shifts towards alternative CSF diversion procedures, such as lumboperitoneal shunting, the application of the CCI scale in iNPH cases treated by these alternative procedures merits further study.The CCI is an easily applicable predictor of survival time in shunted iNPH patients. The lack of a correlation between the CCI and functional outcome means that even patients with multiple comorbidities and limited remaining lifetime may very well benefit from shunt surgery.


Methods: The study included 90 patients with symptomatic irreversible pulpitis of the mandibular molars. Three groups (n = 30 in each group) were included. Group 1: hemophilic patients; group 2: thalassemic patients; and group 3: individuals without any systemic diseases. Onset of LA and visual analogue scale (VAS) scores was recorded immediately after the administration of local anesthesia, during the pulp exposure procedure, and during canal instrumentation, and were compared between the three groups. Frequency distribution, ANOVA, and linear regression analysis (p < 0.05) were applied. Results: The mean onset time was 46 ± 34 s in the hemophilic group, 42 ± 23 s in the thalassemic group, and 38 ± 12 s in controls, but the differences were statistically insignificant. After LA administration (LA-VAS), all three groups experienced a statistically significant reduction in pain (p = 0.048). On pulp exposure (PE-VAS) (p = 0.82) and during canal instrumentation (CI-VAS) (p = 0.55), there was no statistically significant difference in pain perception between the groups. The coefficients indicate a positive correlation between the VAS and onset time, indicating a positive reduction in the VAS following the administration of LA. Conclusions: Hemophilic patients exhibited a clinically longer average onset time for LA. However, the difference among the three groups with regard to the overall pain perception after LA administration, during and after pulp exposure, and during canal instrumentation was statistically insignificant.The study aims to evaluate and compare the onset of local anesthesia (LA) and pain perception during endodontic treatment in hemophilic and thalassemic patients.  Endodontists encounter several types of bleeding diseases in routine clinical practice. The earlier identification of the disorders and their potential systemic causes play a major part in minimizing the risk of bleeding during treatment . HemophiNon-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the management of pain . HoweverProfound pulpal anesthesia  is mandatory for the success of root canal treatment ,13. EffeHence, the objective of this study is to evaluate the onset of local anesthesia and pain perception during endodontic procedures in hemophilic and thalassemic patients, and to compare them with healthy individuals. The null hypothesis was that there would be no difference in the onset of local anesthesia and that the pain threshold levels would be greater or similar in hemophilic patients and thalassemic patients compared to healthy individuals.http//www.strobestatement.org 2018 (accessed on March 2019). The study was approved by the Institutional Ethics Committee of the Institute of Medical Sciences and SUM Hospital, Siksha O Anusandhan (Deemed to be) University, Bhubaneswar, Odisha, India (Ref No/DMR/IMS.SH/SOA/180317), and was conducted in the Department of Conservative Dentistry and Endodontics, Institute of Dental Sciences. Written informed consent was obtained from each participant. The study was conducted during the period 2017–2020. The sample size was determined based on the results from previous studies with . Sample selection and methodology is described in This study was intended and realized according to the STROBE Statements applicable . Group 1: hemophilic patients; group 2: thalassemic patients; and group 3 (control group): individuals without any systemic diseases. “Preoperative pain” response (Pre-op VAS) was recorded using a visual analog scale (VAS). The local anesthesia allergy test  was performed for individuals who had no history of LA administration.The methodology is described in Intradermal test : Test soAll individuals underwent standard electric pulp and cold testing to assess tooth vitality. To verify the readings, contralateral tooth responses were recorded and then performed on the suspected tooth. The teeth were cleaned prior to testing and as an interface medium, a tooth paste  was applied to the buccal crown surface after drying and isolating teeth with a cotton roll. An electric pulp tester (EPT) probe placed on the sound coronal third of the labial surface recorded the patient’s “tingling” sensation. Cold testing with Endo ice  involved placing a large cotton pellet on the buccal surface of the tooth for 15 s or until the patient responded . The patA small quantity of benzocaine gel  was applied at the injection site using a microbrush applicator for 10–15 s. The aforementioned gel was left in contact with the mucosa for two minutes for effective action. Standard inferior alveolar nerve block (IANB) was administered using a solution comprised of 2% lidocaine with a 1:80,000 epinephrine concentration  using 1.8 mL Septodont cartridges  and 27-gauge needles (25 mm in length)  over a 1-min time period. The time of onset (in seconds) of action of LA [VAS score (LA-VAS)] was recorded based on initiation of subjective symptoms (lip/tongue numb) by an independent trained evaluator who was blinded to the study protocol. Subsequently, rubber dam isolation of the tooth was performed, and the treatment was initiated within 15 min of LA administration . Successwww.spss.co.in (accessed on April 2023). The descriptive statistics, including the mean and standard deviation of the scale variables, such as age, gender, and volume, were calculated using the frequency distribution procedure. A comparison of the 3 categories, LA-VAS, PE-VAS, and CI-VAS, with PRE-OP VAS and the mean time of onset of the three groups was performed using the analysis of variance (ANOVA) and linear regression analysis. p < 0.05 was considered to be statistically significant.Statistical analysis: The data were scrutinized, coded, and analyzed using IBM SPSS statistics 24.0  and 21–29 years (36.7%), and the thalassemic group in the age group 30–39 years (36.7) . The hemp = 0.560).The comparison of the mean onset time between the groups is shown in During the pulp exposure procedure, 14 individuals experienced moderate pain, and a repeat volume (1.8 mL) of local anesthetic was administered. As a result, moderate pain was substantially reduced .p = 0.048) in all three groups. On pulp exposure (PE-VAS) (p = 0.82) and during canal instrumentation (CI-VAS) (p = 0.55), there was no statistically significant difference in pain perception between the groups.The comparison of VAS at various intervals is presented in The regression table  indicateBleeding disorders have always been associated with stigma in the field of dentistry. Hemophilia is the most common inherited bleeding disorder . ConversStudies have shown that thalassemic patients are susceptible to dental caries because their caries index is high and they have significantly low salivary phosphorous and IgA concentration ,28. ThisIn the present study, ≥14 years was included because adolescents currently anticipate a normal average life span and an excellent health-related standard of living , and froPain measurement in these two bleeding disorders is challenging as it includes many associated systemic disorders and psychological factors. For pain measurements, the VAS/NRS are proven for quantification . A studyIn the current study, symptomatic irreversible pulpitis was considered, characterized by a sharp pain upon thermal stimulus, lingering pain , spontaneity (unprovoked pain), and referred pain. Postural changes, such as lying down or bending over, can worsen pain, and over-the-counter analgesics rarely work. Deep caries, extensive restorations, and pulpal tissue fractures are common causes. Because the inflammation has not reached the periapical tissues, symptomatic irreversible pulpitis may be difficult to diagnose. In such cases, dental history and thermal testing determine pulpal status . The staIn the present study, the oral hygiene of all groups was considerably good and minor additional clinical findings were treated in subsequent appointments. According to a study, the average onset of LA (Lidocaine) is 1–3 min for subjective symptoms and 1–4 min for objective symptoms . ResearcThe local anesthetic solution comprising 2% lidocaine with 1:80,000 epinephrine is routinely used in endodontics. The use of a vasoconstrictor improves local hemostasis . There aEvery year, about 15 million people worldwide are affected with thalassemia. In India, above 12,000 babies are born with hemoglobinopathies every year. On average, one in every twenty-five Indians is a thalassemia carrier . AdvanceHemophilia is inherited X-linked recessive manner and most prevalent bleeding disorder caused by the deficiency of two coagulation factors: factor VIII (FVIII) or factor IX (FIX) ,43. In IThe hemophilic and thalassemic patients in this study experienced clinically longer onset of local anesthetic action than the control group, but difference was statistically insignificant. Using laser doppler flowmetry, researchers measured the pulpal blood flow in healthy individuals and found that 2% lidocaine  reduced (73%) profound pulpal blood flow at 5 min, with a gradual rebound occurring within 65 min . The delIn clinical studies involving endodontic procedures on patients with irreversible pulpitis, 19 to 56% of patients experienced mild or no discomfort during endodontic access cavity preparation or initial instrumentation on IANB . AccordiIn patients with bleeding disorders, avoiding instrumentation beyond the periapex is essential. As a result, extreme caution was used in the current investigation to avoid instrumentation and filling beyond the apical region of the tooth. The decreased anesthetic effects can be attributed to many reasons, including the fact that the IANB does not always result in significant pulpal anesthesia ,16, as iPatient–dentist variables constitute the limitations of the current study. Since pain is a subjective variable, its depiction on a VAS is affected by an individual’s emotional state and prior anesthetic administration experience . The speIn conclusion, hemophilic patients required a clinically longer onset of LA action, followed by thalassemic patients, but this was statistically insignificant. However, the coefficients indicate a positive correlation between the VAS and onset time, indicating a positive reduction in VAS after the administration of LA. In terms of overall pain perception during and after pulp exposure and during canal instrumentation, there was no statistically significant difference. As a rule, prior to endodontic treatment, patients with hemophilia and thalassemia must undergo factor replacement therapy and a blood transfusion, followed by mandatory antibiotic prophylaxis, to prevent complications.


The treatment of chronic pain with cannabinoids is becoming more widespread and popular among patients. However, studies show that only a few patients experience any benefit from this treatment. It also remains unclear which domains are affected by cannabinoid treatment. Therefore, the present study is novel in that it explores the effects of cannabinoid treatment on four patient-related outcome measures (PROMs), and includes patients with chronic refractory pain conditions who have been given the option of cannabinoid treatment. A retrospective design was used to evaluate the impact of cannabinoid treatment on patients with refractory pain in two German outpatient pain clinics. The present study shows that pain intensity (mean relative reduction (−14.9 ± 22.6%), emotional distress (−9.2 ± 43.5%), pain-associated disability (−7.0 ± 46.5%) and tolerability of pain (−11 ± 23.4%)) improved with cannabinoid treatment. Interestingly, the trajectories of the PROMs seemed to differ between patients, with only 30% of patients responding with respect to pain intensity, but showing improvements in other PROMs. Although the mean treatment effects remained limited, the cumulative magnitude of change in all dimensions may affect patients’ quality of life. In summary, a singular evaluation with pain intensity as the sole outcome does not cover the multidimensional effects of cannabinoids. Therefore, the treatment effects of cannabinoids should be evaluated with different PROMs. In 2017, medical cannabinoids were introduced into the armamentarium of pain treatment in Germany, despite regulatory institutions not approving any of the available substances with this indication . CannabiThe present retrospective observational study included patients undergoing long-term treatment in two university-affiliated specialized outpatient pain clinics in Berlin, Germany. The departments are located at the Charité Campus Mitte and Charité Virchow Klinik. Both clinics focus on outpatient care and provide a wide spectrum of pain interventions, including pharmacological, psychological and physical therapy, thereby composing an ambulatory, multimodal, interdisciplinary therapeutic strategy.Cannabinoid treatment for pain conditions is currently available for patients with severe disease and refractory pain that is not alleviated by standard of care measures. Following a formal request for the assumption of cost from the statutory health insurance of patients, this therapeutic option can be provided.There are various cannabinoid-based therapeutics on the market that differ in terms of their active ingredient content and evidence . Based oThe focus of this study is patients with chronic pain conditions lasting at least six months. In this population, different pharmacologic and nonpharmacologic interventions were evaluated and failed to sufficiently alleviate pain. All patients received pretreatment based on a bio-psycho-social model of disease and were, therefore, seen by physicians and pain psychologists in our pain clinic. Ambulatory multimodal therapy comprised pharmacological, psychological and physiotherapeutic interventions.For the purpose of this study, we included adult patients with chronic refractory pain conditions who had been given the option of cannabinoid therapy from 2017 to 2020. All patients included in this study were adults suffering from long-lasting chronic pain. Patients were excluded if their data were incomplete or if cannabinoid therapy had been provided elsewhere. For the purpose of this study, all available routine data were evaluated from patients’ medical records. During every patient visit to the outpatient pain clinic, we assessed patients using a standardized questionnaire based on a validated German pain questionnaire created by the German Pain Society (Deutsche Schmerzgesellschaft e.V. as a part of the European Federation of IASP) . The queTo assess the overall intensity of pain in the main pain area during the last week, patients were asked “How would you rate the average severity of your main pain in the past week?”. This measurement was reported on a numeric pain scale (NRS), with 0 representing no pain at all and 10 representing maximum pain intensity. Emotional distress is strongly associated with pain and is, therefore, an important aspect of treatment. Patients answered the following question on a 0–10-point Likert scale: “How would you rate your emotional distress in the past week?” A score of 0 represented no emotional distress, and 10 represented maximum emotional distress. “Not relevant, I have no pain at all”;“I can tolerate may pain well”;“I can hardly tolerate my pain”;“I am unable to tolerate my pain any longer”.The tolerability of pain is the extent to which the intensity of pain influences one’s own pain-related tolerance level . PatientThe subjective experience of pain-associated disability has a substantial impact on the development of chronic pain . Patientp < 0.05 indicating statistical significance. Alpha-level adaptation was not applied, according to multiple testing, due to the exploratory study design.This descriptive report uses means and standard deviations for discrete data, medians and 25–75% quartiles for ordinal data or data with skewed distribution, and numbers with percentiles for dichotomous data. Statistical significance was determined using Mann–Whitney-U tests or Fisher’s exact tests. A multivariate logistic regression model was created for each of the four PROMs, including the potentially confounding factors on the independent variable (response to PROMs). To define response, a minimal relevant difference of a 30% reduction in pain-associated symptoms in the PROM domain was defined and calculated as the relative difference from the baseline to the follow-up visit after at least 6-months of therapy. PROMs were, therefore, converted to a binary response variable as an independent variable in the multivariate regression model. Based on previous studies, and to allow for comparability between the different PROMs, the following cofactors were included in all the models: patient age, female sex, cancer pain, neuropathic pain, psychologic comorbidity, duration of chronic pain therapy in months, concomitant co-analgesic use, concomitant opioid use and cannabinoid type (THC versus THC/CBD compound). The regression model fit was assessed using Hosmer–Lemeshow tests, as well as comparative backward-selection regression models. For the purpose of this observational study, data analyses were performed using SPSS 29 (IBM), with In both outpatient pain clinics, more than ten thousand patient contacts were made over a period of four years. Of this population, N = 81 patients were identified as having undergone new cannabinoid treatment during the study period. These chronic pain patients were unresponsive to previous therapeutic interventions, and therefore, cannabinoid treatment was started following the team’s decision. For each of these patients, a formal request was sent to their health care insurance providers to cover the costs of therapy. Altogether, 65% of patients were identified at Campus Charité Mitte and 35% at Campus Virchow Klinikum. Out of these eighty-one patients, N = 70 patients received a prescription for cannabinoids in our two departments. After assessing the patients during a follow-up, complete data were available for analysis in N = 64 cases in the study population .The study population comprised patients with various pain conditions that had lasted for more than 6 months . The stuPain due to malignancy was found in 29.7% of patients (N = 19), and 28.1% of patients (N = 18) suffered from chronic neuropathic pain. Treatment with co-analgesics was provided in N = 43 patients (67.2%), and N = 35 patients (54.7%) received opioids. Cannabinoid treatment was provided at the time of the study, with a median total treatment duration of 25 months (25–75% quartiles: 12–44), and with the longest treatment duration documented at 156 months. The PROMs were assessed within a time frame of about twelve months after the initiation of cannabinoid therapy.® 10/10, N = 1, 2%) and cannabinoid flowers . Of N = 64 patients, most patients  received dronabinol as a prescribed substance. Other preparations included nabiximols , as well as pharmacological preparations  discontinued cannabinoid therapy, three with nabiximols and six with dronabinol. The reasons reported by the patients were mainly side effects , insufficient efficacy (N = 2) and the wish to receive cannabinoid flowers for inhaling, which was not supported by health care insurance (N = 1). Together with the patients, a dose reduction or discontinuation of the use of an ongoing opioid was discussed as one goal of pain therapy via treatment with cannabinoids. The goal of discontinuation was achieved by N = 14 patients (22%), a dose reduction was achieved by N = 6 (9%) and opioid use was maintained in N = 14 (22%) patients.The following are the results of the changes in PROMs due to cannabinoid treatment .p < 0.001, The mean patient-rated pain intensity showed a significant change after patients started treatment with a cannabinoids  were predictors of at least a 30% reduction in mean pain intensity under cannabinoids .p < 0.001) after the start of treatment. This resulted in a mean change in patients’ disability of 1.1 ± 2.3 points  were defined as responders.Multivariate logistic regression analysis showed that cannabinoid type was significantly associated with at least a 30% reduction in pain-associated disability under cannabinoids .p = 0.007). Thus, there was a mean change in emotional distress of 0.8± 2.3 points , and the mean score was 5.9 ± 2.5. After treatment, this emotional distress score was reduced to 5.1 ± 2.6 points  could be defined as responders as they exhibited a clinically relevant change of at least 30% in NRS points.The multivariate logistic regression analysis for the association between at least a 30% reduction in emotional distress and different variables under cannabinoids revealed no significant predictors .p < 0.001), resulting in a mean change in tolerability of 0.4 ± 0.8 points . Before cannabinoid treatment, patients reported poor tolerability of their pain, with a mean of 3.3± 0.7. After the beginning of treatment, this decreased to 2.9 ± 0.8 out of 4 points  of patients with chronic pain that was refractory to previous multimodal treatment. Although the magnitudes were weak, alleviated pain intensity and improved ability to perform daily activities were the most responsive trajectories, with 22% (NNT~5) and 31% (NNT~3) of patients exhibiting at least a 30% improvement in these domains. Approximately 42% of patients were non-responders to cannabinoids in all four PROMs, and only a 5% response rate was observed in all four PROMs. However, the median change in PROMs significantly improved in all four domains, and a relevant frequency of 30% of all patients reduced their dose or ended opioid therapy. To assess the intensity of chronic pain, randomized controlled trials were included in a recent meta-analysis of different diseases. Against a placebo, small but significant effects were described for dronabinol and nabiximol, whereas nabilone, compared with the active control, showed no significant effect . NotablyIn our population, regarding emotional distress, there was a 30% improvement in the magnitude of symptom severity in 29% of patients. This finding has not been previously evaluated with respect to a specific patient-related outcome measurement, and there is no good evidence for major depression. For anxiety, very few data are available, with just one randomized trial demonstrating a modest short-term effect of cannabidiol .Notably, in our population, 22% of patients were able to end opioid treatment, and approximately 10% reduced their doses. This finding is of interest, especially as our population typically received an oral, low-dose cannabinoid, and is in line with findings reporting an opioid cessation rate of 64%  and repoIn our study, we were not able to precisely monitor patients’ discontinuation of cannabinoids. It would be of interest for further research to identify reasons for cannabinoid discontinuation. In a recent systematic review, psychiatric events were the most common adverse event leading to the discontinuation of cannabinoids . AlthougDifferent effects of cannabinoids are closely linked to the interesting intrinsic effects of cannabinoids in mammals. CB1 and CB2 are two G-protein-coupled receptors that can be activated by cannabinoids, and play an important role in the regulation of pain. CB1 receptors are mainly found in the central nervous system, while CB2 receptors are mainly found in the peripheral nervous system and in the cells of the immune system. Moreover, the anti-inflammatory effects of cannabinoids have been linked to the important role of inflammation in different pain disorders. Therefore, both rheumatoid diseases  and chroMore recently, GPR55 was identified in various tissues, including in the brain, immune system and peripheral nervous system ,22. THC, the most-evaluated active ingredient in cannabis, binds to CB1 and CB2 receptors. At the CB1 receptors in the brain, it triggers more psychoactive effects, such as euphoria, sedation and appetite stimulation. The CB2 receptor, which is also described in cells of the immune system and in the peripheral nervous system, regulate inflammation, pain and other immune reactions . Interestingly, THC can also bind GPR55 receptors, producing various effects, including the regulation of inflammation, pain and neurological disorders. CBD binds to CB1 and CB2 receptors with a much lower affinity compared with THC. CBD is not a competitive antagonist, but influences the effects of other substances that bind to CB1 and CB2. CBD acts as an inverse agonist and significantly attenuates the effects of other substances at the receptors . It can The choice of PROMs for cannabinoid therapy should be adapted to the specific needs of the chronic pain patient. Especially complex experiences such as pain are insufficiently identified by simplified measurements, such as single numeric rating scale data, when suffering is exacerbated by functional limitations, anxiety and depression, an inability to perform daily activities, ineffective coping strategies and a lack of pain tolerability . Approximately twenty years ago, core outcome domains for chronic pain trials were recommended, including pain, physical impairment and emotional distress . In moreThe present bicentric study is the first evaluation of patients from two outpatient centers who are receiving medical cannabinoids, in the context of the multimodal treatment of chronic pain, that focuses on different trajectories of pain-related symptoms. However, chronic pain populations in university-affiliated centers may differ from those in other settings. Although it is retrospective in nature, the strength of this trial lies in its stringent assessment of the long-term PROMs implemented in routine care. However, other unmeasured outcomes of potential interest were not assessed, and therefore, did not undergo further exploration in this study. For example, although we possessed good data on co-analgesic and opioid use in this cohort, NSAID usage was not documented with sufficient precision for data analysis, as patients received such drugs often over the counter. As an interesting alternative study design, patients’ and physicians’ perspectives could also be evaluated using a qualitative study methodology. Although no causal inferences can be made based on non-randomized trials, our data were consistent with previous prospective clinical trials, and may lead to a better understanding of PROMs in cannabinoid treatment.Despite about 60% of patients responding to cannabinoid treatment, there is relevant variability in their responses in different domains of outcome measurements. Regarding future research, there is a need to define endpoints for clinical trials addressing PROMs adjacent to pain intensity.


To compare percutaneous balloon compression (PBC) and radiofrequency thermocoagulation (RFTC) for the treatment of trigeminal neuralgia.This was a retrospective single-center analysis of data from 230 patients with trigeminal neuralgia who underwent 202 PBC (46%) and 234 RFTC (54%) from 2002 to 2019. Comparison of demographic data and trigeminal neuralgia characteristics between procedures as well as assessment of 1) initial pain relief by an improved Barrow Neurological Institute (BNI) pain intensity scale of I–III; 2) recurrence-free survival of patients with a follow-up of at least 6 months by Kaplan-Meier analysis; 3) risk factors for failed initial pain relief and recurrence-free survival by regression analysis; and 4) complications and adverse events.p=0.036) but without statistical significance. The only factors that showed a significant influence on longer recurrence-free survival rates were a postoperative BNI ≤ II (P=<0.0001) and a BNI facial numbness score ≥ 3 (p = 0.009). The complication rate of 22.2% as well as zero mortality showed no difference between the two procedures (p=0.162).Initial pain relief was achieved in 353 (84.2%) procedures and showed no significant difference between PBC (83.7%) and RFTC (84.9%). Patients who suffered from multiple sclerosis (odds ratio 5.34) or had a higher preoperative BNI (odds ratio 2.01) showed a higher risk of not becoming pain free. Recurrence-free survival in 283 procedures was longer for PBC (44%) with 481 days compared to RFTC (56%) with 421 days (Both percutaneous interventions led to a comparable initial pain relief and recurrence-free survival with a low and comparable probability of complications. An individualized approach, considering the advantages and disadvantages of each intervention, should guide the decision-making process. Prospective comparative trials are urgently needed. Trigeminal neuralgia is a rare disease characterized by recurrent paroxysmal pain that lasts only for seconds to minutes in the distribution of one or multiple branches of the trigeminal nerve . The IntIn this retrospective single-center study, we identified all patients who underwent PBC or RFTC of the trigeminal ganglion between January 2002 and December 2019 at the Medical University of Vienna to treat medically refractory trigeminal neuralgia. The diagnosis of trigeminal neuralgia was confirmed by reviewing the medical records and identifying typical neuralgia symptoms as defined by the International Headache Society . PatientThe decision of whether to use PBC or RFTC to treat trigeminal neuralgia was made individually by one of three treating surgeons Fig. . FactorsDuring RFTC, intravenous sedation and a nasopharyngeal airway were used. A 20-gauge standard radiofrequency lesioning needle with a straight 5 mm active tip (Radimed®) was inserted through the foramen ovale, positioning the needle tip in the trigeminal cistern as described by Tatli et al. . CorrectAn awake and cooperative patient is not required during PBC and therefore, general anesthesia was used. A 14-gauge cannula was inserted through the cheek and advanced just through the foramen ovale. The inner stylet was then removed. A 4 French Fogarty® embolectomy catheter was passed through the cannula and positioned in the trigeminal cistern with its tip at the trigeminal pore Fig. , A. The Data collection was obtained through patient admission charts, operative notes, preoperative MRT, discharge letters and follow-up reports. The clinical status of the patients was assessed by a neurosurgeon upon admission, discharge and during follow-up examinations. Since follow-up examinations in the outpatient clinic were not carried out in a standardized manner, all patients were contacted and summoned to the outpatient clinic for a personal follow-up visit for the sake of this study. Demographic data, trigeminal neuralgia symptoms including onset of trigeminal neuralgia, duration of symptoms, age at surgery, pain distribution, International Headache Society classification of trigeminal neuralgia  and category of trigeminal neuralgia pain , previous treatment, antiepileptic drugs and the Barrow Neurological Institute (BNI) pain intensity scale were recorded . The BNIComplications during and side effects after the procedures, such as intraoperative bradycardia, hypesthesia, corneal anesthesia, masseter muscle weakness, and anesthesia dolorosa, were noted for all cases, including those interventions that had to be canceled due to an anesthesiologic or a technical problem.Initial pain relief was defined as a BNI of I, II and III with a one-point improvement in the first 4 weeks after surgery. Initial pain relief was documented for all patients who had undergone a successful procedure.Recurrence of trigeminal neuralgia was defined as an increase in BNI after initial pain relief at the operated side. Recurrence-free survival was only calculated if patients had a follow-up of at least 6 months.p-value of < 0.05 was considered statistically significant. Continuous variables following a normal distribution were assessed by analysis of variance and Student’s t-test. Kruskal-Wallis and Mann-Whitney U tests were used for nonparametric interval-scaled variables. Chi-square or Fisher’s exact tests were used for categorical data. Multivariate logistic regression was used to identify individual variables that might influence initial pain relief after surgery. Kaplan-Meier survival analysis was performed with a time interval from surgery to the date of recurring pain and/or increase in antiepileptic medication. If pain was not recurrent, patients were censored at the last follow-up. Survival analysis was performed by using Mantel-Cox log-rank tests to identify individual variables associated with pain recurrence. Multivariate Cox proportional hazard regressions were used to quantify the effect of variables on recurrence-free survival.Statistical calculations were carried out using GraphPad Prism version 9.1.2  and R version 4.1.2 . A two-sided Eligible for the study were 230 patients who underwent 436 procedures with 202 (46%) PBC and 234 (54%) RFTC between 2002 and 2019. Seventeen procedures were terminated prior to ablation and excluded from the initial pain relief and recurrence-free survival analyses. A further 70 procedures had a follow-up shorter than six months and were excluded from the recurrence-free survival calculation , the operating time (p=<0.0001) and the presence of multiple sclerosis (p=0.015). Patients who underwent PBC had a higher median age of 70.5 years, shorter mean operating time of 18.1 ± 9.4 min and suffered less often from multiple sclerosis (30.7%) compared to 66 years, 33.3 ± 14.8 min and 42.7% in the RFTC group.Table Initial pain relief after surgery was achieved in 353 (84.2%) procedures and was well balanced between the two groups, with initial pain relief rates of 84.9% for PBC and 83.7% for RFTC.Multivariate logistic regression analyses showed that patients with multiple sclerosis and patients with a low preoperative BNI had worse initial pain relief with odds ratios of 5.53 and 1.99, respectively Table .Table 2Pp = <0.001) and a BNI facial numbness score ≥ 3 .Recurrence-free survival analysis was performed in 160 patients who underwent 283 (65%) procedures with a slight predominance for RFTC (56%) compared to PBC 44%) . Surgery had to be terminated in 17 (3.9%) procedures because of 1) severe hemorrhage that was not suspended during the operation , 2) the inability to correctly place the needle or the balloon  and 3) the occurrence of an anesthesiologic problem related to the airway or the circulatory function regardless of the intervention (0.9%). Diplopia was encountered in 4 procedures but never in RFTC. Bradycardia commonly seen in ablative procedures had to be treated with medication in 60% of all cases . There was no case of corneal keratitis or anesthesia dolorosa after any percutaneous surgery. When analyzing risk factors for complications, there was no significant correlation with age (p=0.956), previous ablative procedures (p=0.102), ASA comorbidity score (0.411), or the presence of multiple sclerosis (0.351).We encountered an overall complication rate of 22.2% with a mortality rate of 0% Table . The comPBC and RFTC are both minimally invasive techniques that offer good initial pain relief with a low-risk profile. The disadvantage comes with a significant recurrence rate that varies greatly between studies, ranging from 15 to 64% , 37, 39.In our study, we showed that initial pain relief is comparable between PBC 84.9%) and RFTC 83.7%), while recurrence-free survival of PBC was found to be longer but not statistically significant in multivariate analysis, with a median recurrence-free survival of 481 days compared to 421 days after RFTC. After one year, the recurrence rate was 56.1% for PBC and 56% for RFTC. The recurrence rates given in the literature vary widely between 20% - 64% for PBC [%, while % and RFTThis significant difference in the pain recurrence rate between our results and those reported in the literature can possibly be attributed to contrasting definitions of pain relief and recurrence, individual follow-up periods and varying compositions in the patient populations among centers. In our study, the definition of pain recurrence was set very strictly, meaning that every single pain attack and every increase in pain medication was already defined as a recurrence even if the patient improved again afterwards. Others, such as the study by Noorani et al., which showed a recurrence rate of only 25.4% for PBC and 38.2% for RFTC at 1 year, defined recurrence less strict as severe trigeminal pain not fully relieved by medication .The patient population in our study was well balanced between both treatment groups with the exception of age, the presence of multiple sclerosis and the affected division of the trigeminal nerve, reflecting our treatment algorithm over the study period. Patients in the PBC group were significantly older, corroborating the fact that RFTC was performed on awake patients and testing in elderly patients may be complicated by potential cognitive impairment caused by sedation . Likewisn=7 with a preoperative BNI pain intensity scale ≤ 3).Multiple sclerosis and a low preoperative BNI pain intensity scale were found to be the only risk factors for a poor initial pain relief. The influence of the BNI with an odds ratio of 1.99 can easily be explained by the clearer defined difference between the preoperative and postoperative subjectively perceived pain in a very small group of patients  had the highest initial pain relief compared to RFTC (n=15), glycerol rhizolysis (n=89), microvascular decompression (n=10), stereotactic radiosurgery (n=52), and peripheral neurectomies (n=28). In their study, the median recurrence-free survival  for PBC was 17/29 months and only 5/9 months for RFTC, which is comparable to the median recurrence-free survival rate of 370 days (≈12 months) in our study [Mohammad-Mohammadi et al. showed that PBC  of idiopathic trigeminal neuralgia defined by preoperative neuroimaging is likely also based on a vascular-nerve conflict .n = 20), the question if slight hypesthesia has a better recurrence-free survival than no postoperative hypesthesia cannot be seriously answered by our study. However, our data, as well as those available in the literature, allow the bothersome conclusion that a severely damaged trigeminal ganglion leads to a better recurrence-free survival.Only a few studies have addressed predictive factors for long-term symptom improvement after PBC or RFTC. The only factors associated with a longer recurrence-free survival in our study were a low postoperative BNI pain intensity scale ≤ II and pronounced postoperative hypesthesia. Many studies anecdotally describe a positive correlation between postoperative hypesthesia and duration of pain relief , 26. RefWhile isolated third division pain has been shown to be a potential prognostic factor for a longer recurrence-free survival after RFTC, this could not be reproduced in our study . Other sFurthermore, our study population shows a high number of patients needing follow-up surgeries (59.6%), secondary trigeminal neuralgia (42%) and concomitant continuous pain (16.9%). In all three groups, poorer initial pain relief and recurrence-free survival rates have been described in the literature, a finding that could, however, not be reproduced in our single-center series , 26, 41.Both treatment modalities showed zero mortality and an overall complication rate of 25.3% for PBC and 19.7% for RFTC. While this overall complication rate seems high at first glance, one needs to take into account that paraesthesia and a BNI facial numbness score ≥ III were also counted as complications. Anesthesia dolorosa did not occur in any patient, and unwanted ophthalmic hypesthesia occurred in only two patients. The low rates of diplopia, masseter muscle weakness and meningitis are comparable with the current literature . As mostSurgery had to be discontinued in 17 (3.9%) cases, of which 13 (2%) cases were related to the surgical procedure. Reasons for abundance were i) pronounced bleeding in the cheek area and ii) inability to enter the foramen ovale. Both complications are more common with PBC given the larger and therefore more traumatic cannula that needs to be used. Rare causes such as Eagle syndrome with an elongated styloid process and calcified stylohyoid ligament also occurred in our cohort. In these cases, technical adjuncts such as intraoperative navigation could help increase safety.Intraoperative bradycardia occurred more frequently in PBC due to the trigeminal depressor response when entering through the foramen ovale with the larger needle or when inflating the balloon. This well-known phenomenon needs to be communicated with the anesthesiologist beforehand.Like the majority of existing studies on percutaneous interventions for trigeminal neuralgia, this is a retrospective analysis with all the inherent known limitations. Potentially interesting factors that determined initial pain relief and recurrence-free survival in other studies could not be collected, such as the shape of the balloon, which was suggested to represent a key predictor of outcome in PBC , 22. FurBoth percutaneous interventions led to a favorable and comparable initial pain relief in trigeminal neuralgia. In the long run, however, PBC was associated with a slightly but not significantly longer recurrence-free survival than RFTC. At present, there are no randomized controlled trials to seriously compare the effectiveness of ablative interventions. Based on the data currently available to us, both treatment modalities harbor distinct advantages and should be understood as concomitant rather than conflicting procedures. An individualized approach in a center able to offer all available modalities is warranted.


Gynecological malignancy remains a prevalent cause of mortality among women. Chronic cancer pain, as a severe complication of malignancy and its therapies, accounts for a substantial burden of physical and psychological distress in affected patients. Accordingly, early identification, assessment, and standardized management of such pain are crucial in the prevention or delay of its progression. In the present review, we provide a comprehensive overview of the pathological factors that contribute to pain in patients with gynecological malignancy while highlighting the underlying mechanisms of pain in this population. In addition, we summarize several treatment modalities targeting pain management in gynecologic cancer patients, including surgery, radiotherapy, and chemotherapy. These interventions are crucial for tumor elimination and patient survival. Chronic cancer pain exerts a significant impact on wellbeing and quality of life for patients with gynecologic cancer. Therefore, our review emphasizes the importance of addressing this pain and its psychological sequelae and advocates for a multidisciplinary approach that encompasses nursing and psychological support. In summary, this review offers valuable insights into the pathological factors underlying pain, reviews pain management modalities, and stresses the critical role of early intervention and comprehensive care in enhancing the quality of life of these patients. Among tCancer-related pain is a highly prevalent subjective symptom observed in patients with gynecologic malignancies . The nat2Gynecological malignancies encompass tumors that occur in various regions such as the cervix, endometrium, ovary, and other areas Table 1.2.1Cervical cancer is the most frequently occurring malignancy in the female genital tract , 22. Dur2.2Endometrial cancer is a malignant tumor that arises from the epithelial lining of the endometrium, which is the inner layer of the uterus. It ranks second among female reproductive malignancies and is the third most common cause of death in women , 33. The2.3Ovarian cancer is the third most common malignancy affecting the female reproductive system, with the highest mortality rate among all types of gynecological tumors , 44. The3Patients experiencing cancer pain often report it as a subjective feeling that is evaluated comprehensively based on its location, degree, and duration. Various assessment tools are commonly used in the clinic, such as McMillan’s Pain Assessment Form, Visual Analog Scale, and Wong-Banker Facial Expression Scale. The selection of an appropriate assessment method should depend on the patient’s physical condition, cultural background, and level of consciousness .3.1The chronification process of pain in gynecological cancer patients is complex and involves the interaction of various mechanisms. Firstly, ongoing tissue damage and inflammation can lead to the sensitization of peripheral nociceptors, resulting in increased pain sensitivity and decreased pain thresholds. This can lead to a self-perpetuating cycle of pain, as the continuous stimulation of nociceptors can lead to changes in their excitability and trigger the release of pro-inflammatory mediators, intensifying the pain response , 56. Sec3.2Pain is a pervasive phenomenon that can cause physical discomfort and psychological distress in patients, ultimately leading to a reduction in their overall quality of life. Effective pain control is, therefore, of paramount importance for ensuring the well-being of patients. Nurses play a crucial role in pain management and their care has been shown to yield significant benefits . In rece3.3Effective pain management is a critical aspect of cancer patients’ rehabilitation and palliative care. The pain clinic’s management plays an essential role in ensuring standardized pain diagnosis and treatment. It functions as a crucial link and bridge between inpatient and outpatient care. Standardized clinic treatment can enhance the efficacy of treatment while improving patient satisfaction with the quality of medical care . The dev44.1As per the treatment protocol for cancer pain recommended by the World Health Organization (WHO), non-opioid analgesics, weak opioids, and strong opioids are prescribed for patients with mild, moderate, and severe advanced cancer pain, respectively. The representative drugs for each category are aspirin, codeine, and morphine, respectively , 72. Dur4.2Non-pharmacological interventions are recommended for management of cancer pain, which include minimally invasive interventional therapy and physical therapy. Pain due to tumor infiltration and invasion of peripheral sensory nerves is characterized by acuteness, persistence, and progressive aggravation. Mild stimulation can cause severe pain, which can seriously affect patients’ psychological and physiological functions and reduce patient compliance with treatment, posing a barrier to comprehensive treatment of patients , 75. For4.3Patients with advanced gynecological malignancies often experience negative emotions such as pessimism, anxiety, fear, and depression, which can significantly reduce their quality of life and hinder the effectiveness of treatment –81. In o4.4Patients who are at risk of developing pressure sores, respiratory, urinary tract, skin infections, muscle atrophy, and metastasis site symptoms, among others, should receive targeted nursing interventions , 86. Tho4.5Psychosocial interventions had meaningful effects on both pain severity and interference . Meanhiw4.6In recent years, significant advancements have been made in comprehending and treating pain globally. In various regions, extensive research involving continuous care for diverse chronic ailments such as diabetic chronic obstructive pulmonary disease has been conducted and yielded positive outcomes . Additio55.15.1.1Pain management is an essential aspect of patient care, yet it often receives inadequate attention in the medical field. Given that pain is widely prevalent among patients, it is crucial to improve healthcare professionals’ knowledge and competence in this area. Various studies have shown that many nurses in level-1 or level-2 hospitals lack sufficient knowledge of pain assessment methods, particularly when managing cancer patients. As a result, effective pain management is often compromised. Moreover, the lack of time and resources, and the wide range of clinical duties, often limit healthcare professionals’ capacity to provide critical health education and resources to pain-suffering patients and their families.5.1.2The lack of knowledge about pain management among patients and their families often results in patients deliberately enduring pain, as they consider it as a normal experience, without promptly notifying their healthcare providers. This subsequently leads to a delay in receiving the necessary analgesic treatment. Further, several surveys have reported that patients hold a misconception regarding the use of analgesics leading to addiction. This impression causes many patients to discontinue the use of analgesics to avoid dependence and increased drug dosages. The cost of treatment also poses a significant concern for patients, which can result in not adhering to appropriate analgesic therapy.5.1.3As society’s economic status has advanced, the medical profession has similarly progressed. Modern physicians possess exceptional diagnostic and therapeutic capabilities, as well as psychological counseling skills, which enable them to provide personalized treatment regimens tailored to individual patients. It is imperative to emphasize people-oriented thinking and implement standardized pain diagnosis and treatment approaches that prioritize psychological support for patients and their families. This approach aims to assist patients in properly comprehending pain and ultimately achieving effective pain control, thus improving their quality of life. Encouraging patients and caregivers to actively participate in the decision-making process is also recommended as a fundamental component of effective pain management.5.2Outpatient pain management is a crucial component in the standardized management of cancer pain diagnosis and treatment, which has yielded some favorable outcomes. Nonetheless, practical observations indicate that some patients continue to experience moderate to severe pain even after being discharged, and the primary reasons for this are as follows:① Assessing pain in patients in real-time presents a notable challenge. Studies have demonstrated that pain is a subjective phenomenon and that the most reliable and efficacious way to assess it is through the patient’s self-report. Notwithstanding, it is often the case that logistical barriers prevent patients from seeking in-person medical attention, particularly in instances of protracted illness or advanced age. Under such circumstances, family members may be designated as proxies, attending pain clinics in lieu of the patient. Nevertheless, the accuracy of pain assessment and the efficacy of any resultant therapeutic interventions may be compromised by the inability of family members to provide a faithful account of the patient’s pain experience.② The follow-up work was not satisfactory. At present, the follow-up work is only completed by the hospital alone, while most patients return to the local community or family after discharge from the hospital where there is no mature continuous service. It is difficult to guarantee the follow-up rate at 100%, resulting in a majority of patients still suffer pain at home. It is of great importance to establish medical association between community and tertiary hospitals. Additionally, there are problems that the researchers do not have enough awareness and attention of the continuous care, content of continuous nursing remains simple, health education is lack of individualization, research on continuous nursing is not advisable and the system is not perfect, which are issues in need of attention in the future.③ Currently, there is a lack of established demonstration wards for standardized pain treatment, resulting in non-uniformity in clinical pain treatment practices and unresolved issues. Despite the emphasis on individualized treatment, the current state of pain treatment is plagued by several challenges, including primary-stage pain treatment in economically less-developed regions, common instances of inadequate pain treatment, and insufficient familiarity and practical experience with analgesics among clinical medical staff. Moreover, the absence of evidence-based medical evidence exacerbates the aforementioned challenges, rendering the standardization of pain treatment elusive. These challenges signal the imperative need for demonstration wards with standardized pain treatment protocols to facilitate effective clinical management, thereby promoting standardization, and mitigating pain occurrences.④ Continuous care for patients with pain is not performed. In the standardized treatment of pain, nursing staffs play a very important role, for the reason that most cancerous pain is a chronic disease with a long span, and patients often experience aggravation or recurrence of pain due to lack of standard guidance after discharge from hospital. Reports have shown that standardized management of pain-suffered patients should extend beyond the hospital to better ease their suffering. In the future, nursing staffs are supposed to strengthen the continuous care for patients with pain to ensure that the treatment of pain can be effectively continued.5Gynecological malignancy is a prevalent form of cancer that affects the human body. The development and emergence of this disease is primarily linked to several factors, including reproductive history, sexual age, sexual behavior, menstrual history, endocrine function impairments, infections, smoking, excessive alcohol consumption, and other unhealthy habits . The medPatients diagnosed with advanced gynecological malignancies, including cervical cancer, endometrial cancer, and ovarian cancer, experience varying degrees of physical pain. This pain significantly impacts the psychological and physiological wellbeing of patients, ultimately compromising the efficacy of treatment. Consequently, the appropriate diagnosis and management of pain are of utmost importance to improve patient outcomes and reduce suffering . The manOriginal draft preparation, allocation: WW and XH, Manuscript revision, supplement and edition: SL, MJ, and YN. All authors contributed to the article and approved the submitted version.


Background and Objectives: The analgesic effectiveness of epidural adhesiolysis may be influenced by morphological changes in the paraspinal muscles, particularly in elderly patients. The objective of this study was to assess whether the cross-sectional area or fatty infiltration of the paraspinal muscles impacts the treatment outcomes of epidural adhesiolysis. Materials and Methods: The analysis included a total of 183 patients with degenerative lumbar disease who underwent epidural adhesiolysis. Good analgesia was defined as a reduction in pain score of ≥30% at the 6-month follow up. We measured the cross-sectional area and fatty infiltration rate of the paraspinal muscles and divided the study population into age groups (≥65 years and <65 years). Variables were compared between the good and poor analgesia groups. Results: The results revealed that elderly patients experienced poorer analgesic outcomes as the rate of fatty infiltration in the paraspinal muscles increased (p = 0.029), predominantly in female patients. However, there was no correlation between the cross-sectional area and the analgesic outcome in patients younger than or older than 65 years . Multivariable logistic regression analysis indicated that baseline pain scores < 7 (Odds Ratio (OR) = 4.039, 95% Confidence Interval (CI) = 1.594–10.233, p = 0.003), spondylolisthesis , and ≥ 50% fatty infiltration of the paraspinal muscles  were significantly associated with poor outcomes after adhesiolysis in elderly patients. Conclusions: Fatty degeneration of paraspinal muscles is correlated with inferior analgesic outcomes following epidural adhesiolysis in elderly patients, but not in young and middle-aged patients. The cross-sectional area of the paraspinal muscles is not associated with pain relief after the procedure. Lower back pain has been the leading cause of disability for the past 30 years, according to a systematic review . In a coPercutaneous epidural adhesiolysis could be an option to consider for patients who do not show improvement with conservative treatments. The original concept of this procedure included disruption of perineural fibrosis and inhibition of repeated scar formation on affected spinal levels . BecauseSarcopenia, a condition associated with aging, is characterized by a decline in muscle mass, strength, and/or physical performance. In the diagnosis of sarcopenia, changes in muscle quality are emphasized rather than muscle size . IntramuOur study aimed to assess how paraspinal muscle degeneration affects the effectiveness of percutaneous lumbar epidural adhesiolysis in providing pain relief, taking into account the age of the patients. Additionally, we examined whether CSA or fat infiltration rate of the paraspinal muscles is a more useful predictor for analgesic outcome after treatment.Approval for this retrospective observational study was granted by the Institutional Review Board of Yonsei University Health System, Seoul, Republic of Korea (No. 4-2022-1494). The flow diagram of the study is shown in The paraspinal muscles encompassing the multifidus and erector spinae muscles were quantitatively measured on T1-weighted axial MRI images as described in our previous work . To measPreceding each epidural adhesiolysis, transforaminal epidurography was performed to identify filling defects corresponding to the symptomatic levels and abnormalities observed on MRI. Following the completion of sterile preparation and draping, a 22-gauge, 8 cm Quincke tip needle was carefully inserted and advanced beneath the pedicle, with intermittent fluoroscopic guidance in a tunnel view. An anteroposterior view was captured to ensure that the needle tip resided within the lateral half of the pedicle, and a lateral view was obtained to confirm proper placement of the needle tip in the anterior epidural space. To confirm the position, 1–2 mL of contrast media was administered at each level. Once the contrast was confirmed in the targeted area, real-time fluoroscopy was used to assess filling defects.®, Seawon meditech, Bucheon-si, Republic of Korea) was inserted through a guide needle. Upon reaching the target site, 3 mL of the contrast medium was injected to ensure that the catheter was well positioned in the epidural space and spread to the desired target site , documented medical comorbidities, and any history of lumbar surgery. Pain duration, baseline pain score using numeric rating scale (NRS), opioid usage for at least 1 month before adhesiolysis, presence of neurogenic intermittent claudication (NIC) or radicular pain, and good analgesic response on lumbar ESI were identified. The MRI results, evaluated by an independent radiologist, were analyzed for the presence of herniated lumbar disc, and central or foraminal stenosis with grading ,11 and st-test, chi-squared test, or Fisher’s exact test when appropriate. The Mann–Whitney U test was used for continuous variables with non-normal distribution. A multivariable logistic regression model, with backward elimination, was constructed to identify the factors associated with analgesic outcome after adhesiolysis, and the adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated. All statistical analyses were conducted using the Statistical Package for the Social Sciences, version 26.0 . A value of p below 0.05 was considered statistically significant.Descriptive data were expressed as mean ± standard deviation (SD) for continuous variables and as numbers (percentage) for categorical variables. Ordinal data and continuous variables that did not follow a normal distribution are presented as median and interquartile range (IQR). The normality of distribution was evaluated using the Shapiro–Wilk test. Patient characteristics, clinical data, and quantitative measurements of paraspinal muscle were analyzed using independent From 2012 to 2021, 228 patients underwent fluoroscopy-guided lumbar epidural adhesiolysis at our clinic. Out of these, 28 patients were excluded due to meeting the exclusion criteria, resulting in a final enrollment of 200 patients. In 17 patients, analysis of MRI images was difficult due to artifacts. The remaining 183 patients were included in the study; 74 showed good analgesic outcomes and 109 showed poor analgesic outcomes after adhesiolysis .Patients were categorized into two groups based on age: those aged below 65 years and those aged 65 years and above. Patient characteristics, clinical data, and quantitative measurements of the paraspinal muscles were compared between the group with good analgesia and the group with poor analgesia according to age . In patiWe next examined whether the paraspinal muscle mass or fatty infiltration affected the analgesic outcome in patients aged 65 or older according to sex. A high fat infiltration rate of the paraspinal muscles was more frequently observed in female patients with poor analgesia after adhesiolysis, but not in male patients. No significant difference was observed in CSA between male and female patients. In patients under the age of 65, no significant difference in muscle mass or fat infiltration between analgesic efficacies was observed regardless of sex .p = 0.003), spondylolisthesis , and more than 50% fat infiltration in the paraspinal muscle  were independent factors associated with poor post-procedural outcomes of elderly patients. No significant factors related to the efficacy of the procedure was found in patients under the age of 65 (Multivariable logistic regression analysis showed that baseline pain scores of <7 on NRS (aOR = 4.039, 95% CI = 1.594–10.233, ge of 65 .The aim of our study was to identify the relationship between paraspinal muscle degeneration and pain relief following adhesiolysis in patients with degenerative lumbar disease. In this study, higher fatty infiltration of the paraspinal muscles appeared to be an independent factor associated with the analgesic efficacy of adhesiolysis in elderly patients. However, no association was observed between CSA of the paraspinal muscles and pain relief after the procedure.Several factors related to the pain-relieving efficacy of adhesiolysis have been identified ,13, but In this study, in patients aged 65 or older, a higher proportion of fat in the muscle was associated with a poor analgesic outcome; the CSA of the muscle was not related to the outcome. A recent study showed that the CSA of lumbar paraspinal muscles was not a significant predictor of disability or pain scores at 6- and 12-month follow-up in patients suffering from spinal stenosis . In patiIn the present study, we found that female patients with high fat infiltration rate had poor pain relief after adhesiolysis. Several studies have reported that women have higher lumbar paravertebral muscle fatty infiltration compared to men regardless of pain ,21. FurtHowever, paraspinal muscle CSA and quality did not show a significant correlation with the treatment outcome in patients under the age of 65. In a study of 650 Korean patients, the mean densities of multifidus muscle and erector spinae muscle were higher in the young age group compared with the old age group . When thInterestingly, in this study, geriatric patients with higher baseline NRS showed better pain relief after the procedure. A previous study reported that a positive outcome could be expected if patients with failed back surgery syndromes or spinal stenosis had pain scores lower than 9 . HoweverThere are several limitations to this study, including its retrospective design conducted at a single center, small sample size, and relatively short follow-up period. Approximately 16.9% of patients who underwent spinal surgery were included in the study, and these individuals may have unique pain mechanisms and increased paraspinal muscle fat accumulation. However, the presence or absence of spinal surgery did not impact the procedure’s effectiveness in this study. Further research is needed to investigate potential differences in treatment outcomes between patients with and without spinal surgery. The evaluation in this study focused on the cross-section of paraspinal muscles at the L3/4 level, but it is unclear if this accurately represents the total muscle mass and composition. Lastly, although patients with fluoroscopic image data from the procedure were included, detailed contrast dispersion patterns were not analyzed in this study.Our results suggest that fatty infiltration rate of the paraspinal muscles, rather than the CSA, was negatively correlated with analgesic outcome after adhesiolysis in elderly patients. In young and middle-aged patient groups, paraspinal muscle degeneration did not appear to be significantly related to analgesic outcome. These results highlight the potential significance of geriatric rehabilitation, including muscle-strengthening exercise, in patients diagnosed with degenerative lumbar spinal disease.