To quantify the extent to which a standardized pain management order set reduced racial and ethnic inequities in post-cesarean pain evaluation and management.We conducted a retrospective cohort study to quantify racial and ethnic differences in pain evaluation and management before (July 2014–June 2016) and after implementation of a standardized post-cesarean order set (March 2017–February 2018). Electronic medical records were queried for pain scores >7/10, number of pain assessments, and opioid, nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen doses. Outcomes were grouped into 0 to <24 and 24–48 h postpartum, and stratified by race/ethnicity , as documented in the electronic health record. Analyses included logistic regression for the categorical outcome of pain score >7 (severe pain), and linear regression, with propensity score adjustment. Main effect and interaction terms were used to calculate the difference-in-difference in pain process and outcome measures between the baseline and follow-up periods.N=888), severe pain remained more common among NHB patients . Among all patients, pain management processes changed after implementation of the order set, with overall fewer assessments, less Opioids, and more nonopioid analgesics. However, racial and ethnic inequities in a number of assessments and in treatment were unchanged , with the exception of a modest increase in NSAID doses 24–48 h postpartum for Hispanic patients.After order set implementation (A standardized pain management order set reduced overall postpartum opioid use, but did not reduce racial and ethnic disparities in pain evaluation and management. Future work should investigate racial equity-focused education and interventions designed to eliminate disparities in pain management. In prior work, we found statistically significant differences by race and ethnicity in the assessment and treatment of pain following cesarean delivery at our institution.2 In the first 48 h postpartum, non-Hispanic White (NHW) patients received more pain assessments, more nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, and more opioids compared with non-Hispanic Black (NHB) and Hispanic patients. These disparities were present even though NHB and Hispanic patients reported higher pain scores than did NHW or Asian patients; this trend has also been demonstrated at other institutions.3Previous studies in multiple medical specialties have demonstrated disparities in the experience, diagnosis, and treatment of pain between patients of different races and ethnicities.4–6 In October 2016, a new, mandatory protocol was implemented at our institution for pain management after cesarean delivery with the goal of reducing postpartum opioid use. In the new standardized protocol, the anesthesiology team took responsibility for entering a single postpartum pain management order set for all patients. Before the new protocol, post-cesarean pain management orders were usually placed by an Obstetrics service resident using their own personalized order sets.Standardization is a recommended strategy to reduce undesired variation in practice.We sought to determine the extent to which standardization of the post-cesarean pain management order set decreased racial and ethnic inequities demonstrated in our prior work. We hypothesized that this new protocol would not eliminate the previously observed inequities.In November 2017, a standardized order set for post-cesarean pain management was instituted. This is a retrospective cohort study of patients who had live births through cesarean delivery at University of North Carolina (UNC)-Chapel Hill between March 1, 2017, and February 28, 2018. The pain assessment and treatment data were compared with the baseline period, July 1, 2014, to June 30, 2016, which was the timeframe of our prior study demonstrating inequity in assessment and management of pain.Use of the new order set was universally accepted and became part of our Labor and Delivery unit's standard operating procedure. The 5-month delay between order set introduction and the start date of our study period allowed a washout period for the residents, attendings, and nursing staff to familiarize themselves with the new standard of care. Placed by the anesthesiology team at the end of every cesarean delivery, the standardized set included the following: acetaminophen 1000 mg once post-operatively, followed by 650 mg scheduled every 6 h; intravenous ketorolac 30 mg or oral ibuprofen 600 mg scheduled every 6 h for the first 24 h, followed by oral ibuprofen 600 mg scheduled every 6 h; and oral oxycodone 5–10 mg as needed for pain score >7 (severe pain).The order set did not specify frequency of pain assessment. The hospital's nursing policy stipulates that pain be assessed at least once per shift, and as needed per patient request; it requires reassessment of pain within 1 h of any intervention for pain treatment, including as needed pain medications. The nursing ratio is one to every four mother/infant dyads.Data were extracted from the UNC at Chapel Hill electronic health record (EHR) through the UNC Perinatal Research Service Center and the UNC Epic Data Warehouse for Health. Sociodemographic data for the study cohort include maternal age, marital status, insurance at delivery, primary spoken language, site of prenatal care, and self-reported race and ethnicity, as documented in the EHR. The racial and ethnic groups included NHW (referent group), NHB, Hispanic ethnicity, Asian, and Other, which included those patients with unknown race, more than one documented race, or race documented as Native American or Alaskan Native.Clinical data extracted from the EHR include time and date of delivery, maternal body mass index (BMI) , parity, history of prior cesarean delivery, classical cesarean delivery, gestational age at delivery, and whether an infant was admitted to the neonatal intensive care unit (NICU).We excluded from our sample those who underwent cesarean hysterectomies and general anesthesia during delivery, received patient-controlled analgesia or infusion of any intravenous narcotic, had a history of chronic opioid use , or for whom the above-listed clinical or demographic information was missing.Pain scores were indexed 0 to <24 h or 24 to 48 h from delivery to match prior study parameters. Opioid medications administered were tabulated in 5 mg oxycodone tablet equivalents (OTEs) for all opioid medications, including morphine, hydromorphone, codeine, and oxymorphone. The predominant opioid administered was a 5 mg oxycodone tablet, as dictated in the order set. Doses of acetaminophen and NSAIDs such as ibuprofen and ketorolac were also tabulated by 0 to <24 h and 24 to 48 h postpartum.2 we created propensity scores using multinomial regression to calculate the probability that a participant belonged to each of the five race-ethnicity groups as a function of maternal age, BMI, gestational age at delivery, nulliparity, primary versus repeat cesarean delivery, classical versus not classical hysterotomy, and infant admission to the NICU. These propensity scores were used in adjusted regression models.For each racial or ethnic group, we calculated the number of pain scores >7 (severe pain), and total OTEs, NSAID, and acetaminophen doses administered, in the 0 to <24 and 24 to 48 h postpartum periods. Logistic regression was used to analyze the proportion of patients with severe pain scores (>7), and linear regression was used to compare continuous measures by patient race and ethnicity. Following the methodology of our prior study,The purpose of our analysis was to determine whether implementation of a standardized order set narrowed the previously described gap between pain measures in NHW patients and NHB or Hispanic patients. We therefore performed a difference-in-difference calculation to answer, “Did implementation reduce the previously identified inequities in experience of severe pain, number of assessments of pain, and administration of opioid and nonopioid analgesia?” To measure overall change in practice, we used an “intervention x race/ethnicity” interaction term to answer our primary question. For ease of interpretation, we presented least square means for each measure before and after the intervention.Data analyses were performed using SAS 9.4 . The study received approval in accordance with the study center's Institutional Review Board.N=232) comprised 26.1% of the study population, and most NHB patients were in the 25–29-year age group (29.7%). Asian (N=37), Hispanic (N=164), and patients of other races (N=75) were older, with 97/276 patients across these groups 35 years of age or older.A total of 888 patients gave birth by cesarean during the study period and met inclusion criteria. In the follow-up period, NHB patients (N=380) were also relatively older, with the largest proportion in the 30–34-year age group . NHB patients, Hispanic patients, and patients classified as Other were more likely to have Medicaid insurance at delivery . NHW patients were more likely to be nulliparous. Most patients in each group received their prenatal care at our institution, except for Hispanic patients, among whom 55.5% received care elsewhere. The predominant primary spoken language was English, but 29.7% of Asian patients had a primary language other than Spanish or English.NHW patients  Of those who delivered preterm, , NHB patients had the highest rate of preterm birth in the study period, with 46 infants (26.6%) born at <37 weeks of gestation , the post-implementation population (N=888) received less OTEs , more NSAIDs at 24–48 h , and more acetaminophen . NHB, Hispanic, and Asian patients underwent fewer pain assessments at 24 to 48 h , and received fewer OTEs .In the post-implementation period, compared with NHW patients, NHB patients continued to be more likely to experience pain scores >7  for Hispanic patients than for NHW patients. There was no difference in acetaminophen dosing by race-ethnicity from pre-implementation to post-implementation (data not shown).With respect to NSAID dosing, baseline to follow-up changes in number of doses, illustrated by the slope of lines in 7—as a strategy to reduce inequities, we found that for postpartum pain management at our institution, “equal” treatment did not produce equitable outcomes. As previously reported,8 a standardized order set reduced postpartum opioid usage, consistent with other literature showing that standard order sets for cesarean delivery patients decrease opioid usage and lead to shorter hospital stays.10 This is the first study, to our knowledge, that looked specifically at such order sets' impact on racial and ethnic disparities in obstetric patients. Our findings underscore the importance of designing interventions specifically to address racial and ethnic inequities, and of measuring processes and outcomes stratified by race and ethnicity, as advocated for in the Alliance for Innovation on Maternal Health's Reduction of Peripartum Racial/Ethnic Disparities bundle.11While standardization of protocols has been promoted in other obstetric contexts—such as postpartum hemorrhage12 One successful example showed reduction in severe maternal morbidity (SMM) from postpartum hemorrhage for every racial and ethnic group after implementation of a standard protocol across 99 different California hospitals. The reduction in morbidity was greatest for NHB patients, among whom the rate of SMM was highest before the intervention. Effectiveness in that study may have been attributed to the nationally recognized standards and outcome measures for postpartum hemorrhage, which allowed for a clearly defined intervention to be developed. As those authors concluded, the variable effect on disparity reduction seen in quality improvement studies may stem from the fact that the “focus of the intervention alone does not sufficiently address the primary sources of racial/ethnic disparities.”7Maternity care bundles are a relatively recent application of care bundles as a strategy to improve care.13 to maternal deaths15—disproportionately affect patients of color, and cannot be explained by differences in levels of income, insurance status, or access to prenatal care.16That standardized orders did not address inequities in our study calls in to question how implicit bias, institutionalized racism, and discrimination influence health outcomes. Many adverse pregnancy outcomes—from rates of preterm birth17 patients' experiences of pain. A significant limitation of order set implementation, particularly regarding addressing systemic and implicit racism, is that the order set does not incorporate any additional assessment than the once-per-shift assessment per the postpartum floor nursing protocol.Limitations of our study include its retrospective nature, which precludes the ability to survey patients' satisfaction with their post-operative pain management, as well as factors that might influence decisions to accept or decline pharmacologic treatment for pain. Such information will be needed to design more equitable pain treatment strategies. We suggest that additional research explore adjunctive approaches to pharmacologic pain treatment, while incorporating patient input on which cultural and social factors influenceStrengths of our study include consistency with the baseline study's design, strengthening the reliability of our reported results.13 As NHB patients already bear a disproportionate share of SMM, having more than one in three NHB births being through cesarean adds even more undue burden for this population. More equitable post-operative pain control is urgently needed to improve the postpartum experience.On a population level, the impact of disparities in post-cesarean delivery pain experience and treatment is further compounded by the fact that NHB patients have a higher rate of cesarean delivery than NHW patients. In 2019, 35.9% of NHB patients underwent cesarean delivery, compared with 31.3% of Hispanic patients and 30.7% of NHW patients.2 ensuring use of foreign language interpreters for each patient encounter, and3 defining patients' priorities and values in setting expectations for appropriate postpartum pain through qualitative studies and focus groups. Furthermore, we recommend developing protocols with the specific goal of eliminating inequity and devising patient-centered counseling and educational resources to set mutual expectations for postpartum pain and management techniques.Our work suggests several future opportunities for investigation with respect to improved post-operative pain management, such as establishing more concrete guidelines for pain assessment and treatment,Most importantly, increasing public awareness about these inequities will help multidisciplinary care teams identify opportunities for improvement within their own care settings. As intentional as our institution was in designing an order set to address the ongoing opioid epidemic, we need to be as deliberate about eliminating barriers to equitable care for all.


ANI values and changes in intra-operative hemodynamic variables showed statistically significant correlations. For predicting post-operative pain, pooled sensitivity, specificity, and DOR of ANI were 0.90 , 0.51 , and 3.38 , respectively. ANI monitoring in patients undergoing surgery under general anesthesia is a valuable measurement for predicting intra- and post-operative pain. It reduces the use of intra-operative opioids and aids in pain management throughout the perioperative period.The analgesia nociception index (ANI) has emerged as a potential measurement for objective pain assessment during general anesthesia. This systematic review and meta-analysis aimed to evaluate the accuracy and effectiveness of ANI in assessing intra- and post-operative pain in patients undergoing general anesthesia. We conducted a comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, public clinical trial databases , and OpenSIGLE to identify relevant studies published prior to May 2023 and included studies that evaluated the accuracy and effectiveness of ANI for intra- or post-operative pain assessment during general anesthesia. Among the 962 studies identified, 30 met the eligibility criteria and were included in the systematic review, and 17 were included in the meta-analysis. For predicting intra-operative pain, pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under curve of ANI were 0.81 (95% confidence interval [CI] = 0.79–0.83; I Anesthesia required for surgical procedures consists of three interrelated components: hypnosis, analgesia, and muscle relaxation. Balanced anesthesia maximizes effectiveness while minimizing side effects by appropriately adjusting multiple anesthetic agents that target these three components to achieve stability and prevent unwanted autonomic reflexes. Accurate assessment of each component is crucial for optimal anesthesia. In particular, the assessment of nociception and effective pain management are of the utmost importance, as they are closely associated with post-operative pain intensity and complications.Pain is a subjective experience that involves an intricate process of signal transmission within the autonomic nervous system (ANS) and central nervous system (CNS), spanning the spinal cord, brainstem, and thalamus. Consequently, several pain assessment methods have been developed. In the past two decades, diverse monitoring tools have been devised to evaluate nociception, which refers to physiological responses to noxious stimuli ,2. WhileOwing to the overlapping neuro-anatomy between pain transmission and ANS pathways, pain induces changes in ANS activity, particularly an increase in sympathetic nervous system activation and a decrease in the parasympathetic nervous system . ANS-basVarious studies ,5,6 havehttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021277720) accessed on 10 October 2021. This study was conducted in accordance with the recommendations of the Cochrane Collaboration ,526,52] ,526,52] ctively) .Seven studies reported the AUC of accuracy in predicting intra-operative pain, which was detected using hemodynamic reactivity ,39,44,572 = 87.4%, Pchi2 < 0.001)   A. A sens< 0.001) B. Theert< 0.001) .p = 0.5) in patients without hemodynamic reactivity, whereas other studies have shown significant decreases in ANI after intubation [Other studies that were not included in the meta-analysis also indicated that the ANI reflects the degree of pain or analgesia . Some sttubation ,42,47, stubation ,47, and 2 = 58.7%, Pchi2 = 0.064; 0.51, 95% CI = 0.49–0.52, I2 = 99.9%, Pchi2 < 0.001; and 3.38, 95% CI = 2.87–3.88, I2 = 81.2%, Pchi2 = 0.001, respectively)   . Sensiti= 0.599) .One study , excludep = 0.085), all other studies had statistically significant results.Four studies ,45,56,61Eight studies (255 patients in control group and 261 patients in opioid group) investigated the association between intra-operative opioid use and ANI monitoring (GRADE evidence: low). Among these studies, two  used fen2 = 79.24, Pchi2 < 0.001). Subgroup analysis showed reduced intra-operative opioid use in the ANI group when remifentanil was used , but not when fentanyl, morphine, or sufentanil was used.   . Howeverctively) .This systematic review and meta-analysis of 30 studies demonstrated that ANI monitoring during surgery can assist in predicting pain in patients during and after the surgical procedure. It also correlates with hemodynamic variables and a reduction in the use of intra-operative opioids during surgery. ANI monitoring, which has no additional risks apart from electrode attachment risk, yielded positive results. These findings contribute to maximizing the benefits of clinical application of ANI.In clinical practice, adjustments to the administration of narcotic analgesics, inhalation agents, and intravenous anesthetics during general anesthesia are commonly made based on the clinician’s judgment with the aim of stabilizing vital signs. This is achieved by observing the patient’s physiological reaction to nociception, such as hemodynamic changes, sweating, or movement. For instance, if blood pressure or heart rate increases or the patient moves, physicians often attribute this to intra-operative pain and increase the dosage of opioids administered. However, it is important to note that clinical scenarios are not always dichotomous, and a significant number of patients with elevated blood pressure do not necessarily have inadequate analgesia and may not require additional analgesics. Logier et al.  reportedOne of the methods of assessing the validity of ANI is to compare its correlation with that of hemodynamic monitoring. ANI values, which reflect intra-operative pain in this study, have been found to be significantly correlated with hemodynamic variables. The majority of studies ,45,61 inA more effective criterion for validating ANI could involve a comparative analysis of ANI changes in response to nociceptive stimuli. ANI changes in the presence or absence of stimuli at various opioid concentrations and following the administration of analgesic agents, such as opioid boluses. Various studies exploring different nociceptive stimuli have demonstrated that ANI values reflect the responses to these stimuli ,6,52. ANp < 0.05). Similarly, Kommula et al. [For instance, Susano et al.  reporteda et al.  found a This study also found that ANI monitoring reduced the intra-operative opioid use. However, the results varied depending on the type of opioid used. These differences may be attributable to variations in opioid pharmacokinetics. For example, remifentanil has a rapid onset and a short duration of action, making it relatively insensitive in the context of administration. In contrast, opioids, such as morphine or sufentanil, have a slower onset and longer duration of action, thus posing challenges in terms of titration and potentially resulting in significant fluctuations in the concentration of the drug at the site of action . The pha2 = 0.33, p < 0.01) between ANI levels immediately before extubation and pain scores using the NRS upon arrival in the PACU. Another study [2 = 0.41, p < 0.05) between ANI and NRS scores upon arrival at PACU.This systematic review and meta-analysis also showed ANI exhibited good performance for predicting post-operative pain. Although not included in the quantitative analysis, studies have indicated that ANI values not only reflect intra-operative nociception during surgery, but also post-operative pain. For example, one study  found a er study  showed aHowever, pain scores reported by patients are highly subjective, and ANI values are affected not only by the pain itself but also by the level of alertness and psychological stress of conscious patients, such as those after surgery . TherefoThis study had several limitations. First, after a comprehensive and sensitive search, only 30 studies were included. Some outcomes may have been underpowered; therefore, the findings of this study are inconclusive. Second, in most studies included for predicting intra-operative or post-operative pain, the threshold of ANI was not prespecified, which may have led to overly positive or negative estimates of sensitivity and specificity. Third, many studies we included were retrospective rather than prospective, which leads to a higher risk of bias in patient selection and index test domains. Fourth, considerable heterogeneity was observed in some outcomes. This may be due to variations in the types and severity of surgeries, differences in anesthesia protocols, variations in the use of analgesics, and differences in dosages among the included studies. Fifth, this review only included patients who underwent general anesthesia, as the review aimed to evaluate the validity of ANI for a specific question. Therefore, the validity of these results may differ between patients who are sedated and awake.ANI monitoring during surgery can assist in predicting patient pain both during and after the surgical procedure. It also correlated with changes in hemodynamic variables during surgery and a reduction in the use of intra-operative opioids.


Muscle pain and stiffness are strictly interconnected. Injuries frequently occur during sport activities, causing muscle pain, with or without stiffness, and require effective as well as fast-acting treatments. Topical products can be ideal for the treatment of such physical alterations as they are convenient and simple to use. In this study, it was investigated the application of a novel topical formulation, EGYFIL™, for the treatment of pain and stiffness due to muscle contracture, trauma, and/or overtraining. The lotion is composed of hyaluronic acid, a well-known ingredient for the pain alleviation, mixed with skin conditioning SH-Polypeptide-6 and SH-Oligopeptide-1, embedded in it.Twenty-six patients with pain and/or stiffness were enrolled. After a screening visit , patients were treated for the first time with the IP. The treatment consisted of topical application of the pain lotion. Level of pain and stiffness were measured with Numerical Rating Scale (NRS). Patients’ pain and/or stiffness were evaluated at t0 (prior to using the product), after three hours (t1), and after three days (t2) of treatment. Participants were free to apply and re-apply the product ad libitum over the course of the study period (3 days). Potential adverse events (AE) and tolerance were evaluated during each visit.p < 0.001), followed by an additional 20% decrease after three days (p=0.0873). Overall, there was a 42% decrease in pain over the three days of the study (p =0.001). Furthermore, a 24% reduction in stiffness in the first three hours (p=0.025) and a 38% decrease in stiffness over three days (p < 0.001) were observed. Reduction in pain and stiffness were neither age, nor sex dependent. No adverse effects were reported during the study.There was a 22% decrease in pain in the first three hours (EGYFIL™ is safe and seems to reduce pain and stiffness in patients during the 3 days of treatment, already after 3 h from the first application.ClinicalTrials.gov ID: NCT05711953. This trial was registered on 03/02/2023.The online version contains supplementary material available at 10.1186/s12891-023-06903-y. Stiffness is a prelude to musculoskeletal pain , 2. MyofMechano-molecular pathways associated with myofascial tension can lead to musculoskeletal pain , 9. MyofHyaluronic acid (HA) is a hygroscopic glycosaminoglycan often utilised for the treatment of articular pathologies due to the elastoviscous property conferred by the polymer: it is thought to increase the viscoelastic and shock absorbing properties of the synovial fluid while also reducing the inflammation and pain in joint diseases of the knee or hip, more typically in over-weight patients –24. HA hIn EGYFIL™, two specific peptides are included in the lotion to promote the functional relief of pain and stiffness. SH-Polypeptide-6, derived from the interleukin-10 (IL-10) starting protein: SH-Polypeptide-6 carries IL-10's anti-inflammatory activity by engaging signals that modulate NF-kB pathways, downregulating pro-inflammatory cytokines TNF, IL-6, IL-1 and IL-8 , 41. LikThe other peptide in EGYFIL™, SH-Oligopeptide-1 is synthesized from starting protein Epidermal Growth Factor (EGF). In the connective tissue matrix, EGF inhibits kappa B (NF-κB) pathway I and protects osteoblasts from inflammation and oxidative injury . SH-OligThis prospective pre-market, interventional, single arm investigation aimed to enrol participants with stiffness, inflammatory pain, or both stiffness and pain, to evaluate the effectiveness of the Investigational Product (IP), EGYFIL™, a topical lotion.The study was approved by the independent Ethics Committee of International Institute of Clinical Ecology (IICE), . The study was conducted according to the ISO 14155:2020, Good Clinical Practice guidelines, laws regarding the use of personal data (EU 2016/679), local Italian laws (196/2003) and the World Medical Association Declaration of Helsinki. This clinical trial was registered on 03/02/2023 with the following ClinicalTrials.gov ID: NCT05711953.Initial examination and assessment were performed by the PI immediately following consultation.Inclusion and exclusion criteria are indicated in Table The maximum time of treatment for each enrolled patient was 3 days. Following an explanation of the aims of the study, patients that met all the inclusion criteria and none of the exclusion criteria, after having signed the informed consent form (ICF), entered the screening phase during which the baseline tests was conducted. At the baseline visit (t0), according to the instructions for use (IFU) and the judgement of the principal investigator (PI), the enrolled subjects were treated for the first time with the IP. The treatment consisted of topical application of the pain lotion immediately following the baseline visit. Primary endpoints, pain and stiffness, were both assessed through the use of a numerical rating scale (NRS) where zero corresponded to no pain/stiffness, and 10 represented the maximum possible pain/stiffness. Participants were asked about their pain and/or stiffness prior to using the product (t0), after three hours from the first treatment (t1), and after three days (t2) through phone contact and by means of NRS for pain and a questionnaire .Analyses were performed comparing each of the three timepoints with each other. Distribution of data was tested for normality by D’Agostino-Pearson tests. According to the result of this test, one-way ANOVA test with Tukey’s post hoc test were used to analyse the differences in the NRS between study visits. Unpaired t-tests were used to compare non-matched groups . In the study, 26 patients were enrolled. All 26 enrolled patients completed the study. However, 3 patients used other analgesic products during the course of the study and were therefore excluded from the protocol set. Of the 23 remaining patients, 12 (52%) were male and 11 (48%) were female , complained of both pain and stiffness, with 7 (30%) complaining of pain only, and just 2 (9%) participants with only stiffness , followed by an additional 20% decrease after three days relative to 3 h (p = 0.0873). Overall, there was a significant (p = 0.001) 42% decrease in pain over the three days of the study  and correspond to a 24% reduction in stiffness in the first three hours and a 38% decrease in stiffness over three days .When asked at both 3-h and 3-day intervals, most patients reported that reapplying the product maintained the initial symptom relief Fig. . There w2 = 0.13).There was a weak, but positive correlation between mean response (mean of 0-3 h and 3 h-3d responses) and satisfaction score . A robust response was seen in all groups. Similar results were seen for the reduction of stiffness at both 3 h (24%) and 3 days (38%) timepoints. Although it is not a standard scale to evaluate the stiffness, the use of NRS to assess this condition is not a completely novelty: it was already used to measure stiffness following small molecule therapy and tenosynovial giant tumor , 50 and Concerning the pain, the effectiveness of EGYFIL™ is comparable to other drug-based topical treatments. Normalizing data to the relative t0, in patient with ankle pain, where non-surgical treatments are the first choice, in case of acute lateral sprains , long-te. showed that concentrations as low as 0.01% (0.25 mg/2.5 ml) of hyaluronate provided relief from OA pain [Hyaluronic acid has been used successfully for the treatment of pain in a variety of pathologies, most notably in osteoarthritis and joint pain via intra-articular injection , 60–63,  OA pain , and res OA pain . Indeed, OA pain . Somethi OA pain , 65, 66.Additionally, topical application of HA and other large molecules can benefit through the use of penetration enhancers, such as glycerol, which has been shown to increase the transdermal penetration of HA almost 200 time more than HA in water .This study has some limitations, in that it is a single arm study and thus cannot exclude the natural and physiological resolution of the symptoms over time. However, the data collected during the study highly suggests that the application of the lotion has a profound effect on reducing stiffness and pain in an expedited time frame, demonstrating that the lotion has a beneficial effect at quickly reducing discomfort over large body zones. Although acceptable from a statistics point of view, a further study into the mechanism of action, within a larger cohort of patients, including a control group, is warranted. Another limitation of the study is the absence of a follow-up later than three days, to verify if the positive effect of EGYFIL™ treatment continued once the application is interrupted. Finally, a more precise diagnosis before the treatment, could better identify the most suitable conditions for the alleviating efficacy of the lotion.The study herein shows that EGYFIL™ lotion appears to be safe and well tolerated by all patients exposed to its treatment. The reduction of both pain and stiffness over the course of the study, evaluated by Numerical Rate Score, revealed a quick response rate in relieving discomfort within three hours and significantly reduced pain and stiffness within three days, suggesting that the product can be effective for use in the treatment of stiffness and pain-related complaints in both sexes, in all age groups. No adverse reactions were recorded or observed throughout the study, denoting the product’s safety in repeated application.Additional file 1. Additional file 2: Supplementary Table 1. Patients’ NRS pain and stiffness scores for each time-point.


High-dose-rate brachytherapy (HDR) is part of the main treatment for locally advanced uterine cervical cancer. Our aim was to evaluate the incidence and intensity of pain and patients’ satisfaction during HDR. Risk factors for suffering pain were also analyzed. A retrospective study was carried out by extracting data from patients who had received HDR treatment for five years. Postoperative analgesia had been administered using pre-established analgesic protocols for 48 h. Pain assessment was collected according to a protocol by the acute pain unit. Analgesic assessment was compared according to analgesic protocol administered, number of needles implanted, and type of anesthesia performed during the procedure. From 172 patients treated, data from 247 treatments were analyzed. Pain was considered moderate in 18.2% of the patients, and 43.3% of the patients required at least one analgesic rescue. Patients receiving major opioids reported worse pain control. No differences were found regarding the analgesic management according to the intraprocedural anesthesia used or the patients’ characteristics. The number of inserted needles did not influence the postoperative analgesic assessment. Continuous intravenous infusion of tramadol and metamizole made peri-procedural pain during HDR mild in most cases. Many patients still suffered from moderate pain. Cervical cancer is the second most common gynecological malignancy worldwide . High-doPeri-procedural pain during HDR is frequent, but its incidence remains unknown. There are multiple causes of postoperative pain in these patients that should be prevented. However, limited data published to date are based on studies analyzing the incidence and intensity of pain during the needle’s insertion ,12,13,14The aim of this study was to evaluate the incidence and intensity of pain during the 24 h after needle insertion for HDR and the satisfaction of the patients regarding postoperative analgesia with the different analgesic protocols used in our center. As a secondary objective, intensity of postoperative pain was evaluated in relation to the intraoperative anesthesia used, the characteristics of patients, and the number of needles inserted for the therapy.Once the approval of the ethics committee of the Hospital Universitario de Gran Canaria Doctor Negrín was obtained (reference 170128), we carried out a retrospective study. Inclusion criteria were all patients who had undergone HDR for cervical cancer from November 2012 to November 2017. Exclusion criteria were age under 18 years old, cognitive impairment, and cognitive disabilities. Cases in which postoperative data collection had not been fully recorded were also excluded. This manuscript follows the STROBE guidelines .The choice between general or neuraxial anesthesia for needle insertion was made based on medical considerations or on the patient’s preference. If neuraxial anesthesia was selected, it was performed in the sitting position using 10 mg of 0.5% bupivacaine associated with 10 mcg fentanyl through interspace L2–L3 or L3–L4 to reach a level of sensitive block at dermatome T7–T10. Cases in which general anesthesia was chosen, total intravenous general anesthesia with propofol in continuous infusion associated with 50 mcg fentanyl was used. Mechanical ventilation of patients submitted to general anesthesia was managed using a laryngeal mask. Regardless of the anesthetic treatment carried out during implantation, all patients were given an intravenous dose of the analgesic drugs they would then receive in continuous infusion for the next 24 h.Postoperative analgesia was given following standardized analgesic protocols designed by the acute pain unit of our hospital, combining different types of drugs administered by electric pumps of continuous perfusion during the 24 postoperative hours . The choThe acute pain unit of our service performs daily protocolized follow-up of the analgesic management of patients. Twenty-four hours after the first treatment and just before the second treatment, a doctor from the acute pain unit visited the patient in the ward to assess the analgesic management. The Visual Analogue Scale (VAS) was used to assess pain intensity using a 10 cm line with two extreme points, representing “no pain”—0—and “maximum pain imaginable”—10. In this medical interview, the physician asks the patient to assess the current pain by placing a mark on that line. Subsequently, a ruler is used to measure the distance in centimeters from the “no pain” point to the mark made by the patient. Based on this scale, postoperative pain was categorized into mild (VAS 1–3), moderate (VAS 4–7), and severe (VAS 8–10).To evaluate patients’ satisfaction in relation to the analgesia received, the subjective assessment scale (SAS) was used. In this medical interview, the physician asks the patient to describe the satisfaction with the management performed using the following categories: excellent, good, fair, and poor. After carrying out the daily protocolized assessment, the physician in charge of the acute pain unit (not involved in this study) enters the data into the unit’s database.While reviewing medical records, the following data were collected: age, weight, height, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status, medical and psychiatric comorbidities, drug allergies, toxic habits, and chronic pain analgesic consumption. We also recorded the anesthesia used during the needle placement, the number of needles implanted, and the analgesia administered throughout and after the procedure. We also collected the following data from the acute pain unit database: the protocol of postoperative analgesia administered, the pain intensity assessment, the number of analgesics required during the 24 h period after needle implantation, the side effects of the analgesic medication, and the overall patient satisfaction regarding the postoperative management.To assess the analgesic quality based on the number of needles inserted for HDR, the patients were stratified into four groups: group 1 , group 2 (1–5 needles), group 3 (6–10 needles), and group 4 (more than 10 needles).t-test for independent samples was used in cases of variables with normal distribution and the Mann–Whitney U test when the distribution of the variables could not be adjusted to normality. To compare quantitative variables among more than two groups, the one-way analysis of variance (ANOVA) test for independent samples was used in cases of variables with normal distribution and the Kruskal–Wallis test in cases where distribution was not adjusted to normality. A p-value < 0.05 was considered statistically significant. Data were analyzed using SPS 24.0 .Qualitative data were expressed as absolute and relative frequencies. Quantitative variables were expressed as mean + standard deviation (SD) in cases of normal variables and median and interquartile rate (IQR) if their distribution was not adjusted to normality. The Kolmogorov–Smirnov test was used to analyze the normality of the data. The analysis of the results of qualitative variables was performed using the Chi-square test. To compare quantitative variables between two groups, the During the study period, 172 female patients received 260 HDR treatments. Of these patients, data could not be fully retrieved for 18 patients. After excluding these cases, 154 patients who had received 247 treatments were analyzed. Descriptive analysis of the sample is shown in Mean VAS during the first 24 h after needle implantation was 2.56 ± 1.04. Pain was considered mild (VAS 1–3) in 81.8% and moderate (VAS 4–7) in 18.2% of cases. No patient presented a VAS higher than 8. During the first 24 h, extra-analgesic medication had to be administered to the 43.3% of the patients. The frequency of the analgesic protocols prescribed and its relationship with pain assessment during the first 24 postoperative hours  are shown in n = 40) showed a mean VAS of 2.40 ± 1.01, similar to that shown by patients without this diagnosis  (p = 0.293). No differences were found in terms of the VAS based on smoking habit (p = 0.141), alcohol abuse (p = 0.256), or preoperative consumption of chronic analgesics (p = 0.077).Neuraxial anesthesia was selected during the needle placement for most patients. p = 0.643) or SAS (p = 0.935) based on the number of needles inserted. We also found no differences in terms of the analgesic protocol administered in relation to the number of needles inserted (p = 0.508).The average VAS based on the number of needles inserted for the treatment is represented in p = 0.483), the analgesic protocol established (p = 0.093), or the number of extra-analgesics required (p = 0.055). Nor was there a relationship detected between side effects and postoperative VAS (p = 0.893) or the number of needles applied (p = 0.791).In 5 of the 247 treatments analyzed (2%), nausea was a side effect of postoperative analgesia. No mortality or severe complications related to the analgesic management were observed during the first 24 h of treatment. We found no relationship between adverse effects and the type of anesthesia applied for needle placement (This study shows that up to 18% of patients undergoing HDR suffered moderate pain during the first 24 h. In addition, 21.4% of patients assessed the received analgesia as fair or poor. Postoperative pain is a frequent cause of delay in hospital discharge and has been shown to increase postoperative morbidity and mortality . IncreasThe placement of needles for HDR treatment was performed under anesthesia for all patients in our center. The presence of an anesthesiologist in the brachytherapy team is common in the USA and Europe, having become a key element that allows for optimal levels of analgesia and comfort during therapy ,8. HowevIt was difficult to assess optimal anesthetic management during needle implantation with our study due to the disparity of published treatments ,27,28,29Diagnosis and treatment of cancer is considered a major stress in life and can cause or aggravate psychological disorders . These pA worse quality of analgesic management could have been expected in patients in which a greater number of needles was implanted. However, taking into account that the main reason for suffering from pain after the needle insertion is the dilation of the cervix and the upper third of the vagina , the numWe acknowledge some limitations of our study. The main one is its retrospective nature. However, the acute pain unit of our service carried out a strict protocol during the postoperative follow-up, collecting all data related to the pain daily and objectively, and data loss was rare. In addition, there were variables that were not taken into account in this analysis that could have affected the analgesic assessment of patients, such as tumor stage. Since this is a retrospective study in which routine clinical practice carried out over 5 years was evaluated, it was not possible to establish a baseline control group. A prospective analysis could confirm data obtained and allow for the investigation of other variables that were not studied, and a randomized clinical trial could confirm which one is the best analgesic alternative. Second, we did not focus on the evolution of patients after hospital discharge. Since the period under review covered five years, it was difficult to compare the evolution of patients without taking more variables into account. It would have been interesting to evaluate other characteristics, such as the number of hospital readmissions or visits to the emergency department due to pain after hospital discharge, the intensity of pain beyond 24 h after the procedure, the worsening of patients’ psychiatric comorbidities, the incidence of chronic pelvic pain after therapy, cancer-free time, or survival. However, the collection time would be too long and impractical for many of these variables in a study focused on analyzing postoperative acute pain.Patients with cervical cancer undergoing HDR experience pain and distress. Postoperative analgesic management using continuous intravenous infusion of combined tramadol and metamizole protocolized and adapted to the clinical characteristics makes postoperative pain mild in most cases. However, many patients still suffer from moderate pain.Postoperative analgesic management can be optimized to increase satisfaction levels. The number of needles inserted for the therapy does not seem to be a risk factor for worsening acute postoperative pain in HDR. The presence of psychiatric disorders such as anxiety or depression makes it difficult to manage postoperative pain. Therefore, attention to the examination of psychological and psychiatric factors may be more important than the mere administration of strong opioids.


Patients with the placement of a totally implantable venous access port (TIVAP) commonly suffer from pain caused by inserting a non-coring needle. At present, lidocaine cream and cold spray are extensively used for pain management, but they are complex to manage in busy medical environments and developing countries. The lidocaine spray combines the analgesic effect of lidocaine cream and the rapid onset of cold spray, which can effectively alleviate the pain related to non-coring needle puncture in patients with TIVAP. This randomized-controlled trial aimed to explore the effectiveness, acceptability, and safety of lidocaine spray in relieving the pain of non-coring needle puncture in patients with TIVAP.n=42). Before routine maintenance, the intervention group received lidocaine spray 5 min before disinfection, while the control group received water spray 5 min before disinfection. The main clinical outcome was pain, and the degree of puncture pain in both groups was evaluated using the visual analogue scale.A total of 84 patients who were hospitalized in the oncology department of a Grade III Level-A hospital in Shanghai from January 2023 to March 2023 and were implanted with TIVAP and required non-coring needle puncture were selected as the study subjects. The recruited patients were randomly assigned to the intervention group and the control group (P>0.05). The pain score in the intervention and control groups was 15.12±6.61mm and 36.50±18.79mm, respectively (P<0.001). There were 2 (4.8%) patients with moderate pain in the intervention group and 18 (42.9%) patients with moderate pain in the control group (P<0.001). In the control group, 3 (7.1%) patients reported severe pain. The median comfortability score for the two groups of patients was 10, but there was a difference between the two groups (P<0.05) because the intervention group tilted to the right. The successful puncture rate of the first time puncture had no difference between the two groups, both being 100%. Moreover, 33 patients (78.6%) in the intervention group and 12 patients (28.6%) in the control group reported that they would choose the same spray for intervention in the future (P<0.001). During the 1 week of follow-up, 1 patient in the intervention group developed skin itching (P>0.05).There were no significant differences between the two groups in age, gender, educational level, body mass index, port implantation time, and disease diagnosis  The totally implantable venous access port (TIVAP) is a subcutaneous infusion system that can be retained in the human body for a long time . By virtThe pain management of non-coring needle puncture is mainly divided into non-pharmacology and pharmacology, such as the use of virtual reality, Vapocoolant spray, cryotherapy, cutaneous stimulation therapy, lidocaine cream, and lavender essential oil , 12, 13.The main component of lidocaine spray is lidocaine, which achieves the surface anesthetic effect by accumulating at the cortical pain receptors and nerve endings. Local anesthesia can be produced 1–2 min after spraying, and the duration is 15–20 min. Compared with lidocaine cream and Vapocoolant spray, lidocaine spray has the advantages of quick onset, long duration of anesthesia, and convenient use. Some researchers have used lidocaine spray to relieve pain related to venipuncture, radial artery puncture , 19, insIn this parallel randomized controlled trial, 84 patients who were hospitalized in the oncology department of a Grade III Level-A hospital in Shanghai from January to March 2023 were selected as the study subjects. All these patients were implanted with a chest wall TIVAP and required non-coring needle puncture for infusion. After admission, these patients were randomly assigned to the intervention group (42 cases) and the control group (42 cases). Inclusion criteria were as follows: ① age ≥ 18 years old; ② no history of mental illness, normal cognition, and clear language expression; ③ normal pain response; ④ intact skin at the injection port, without damage, redness, or infection. Exclusion criteria were the following: ① long-term use of analgesic drugs; ② allergic to lidocaine. This study was approved by Human Trial Ethics Review Committee of Shanghai General Hospital, and all subjects provided informed consent and voluntarily participated in the study.In Excel, a column of numbers 1–84 was established as column A. After numbering, column B of 84 corresponding random numbers was generated using a random function. Column A and column B were all selected and sorted in ascending order of column B, so that 84 numbers in column A were randomly arranged, with the first 42 random numbers assigned to the control group and the last 42 random numbers assigned to the intervention group. Then, the 84 randomly numbered cards were sequentially placed into 84 envelopes and the envelopes were ordered. After the patient agreed to participate in this study, the operator opened the envelopes sequentially according to the envelope number and obtained the random number and corresponding grouping. The patient did not know the grouping situation.In this parallel randomized controlled trial, the intervention group was subjected to lidocaine spray treatment, while the control group was a blank control, and the pain score was the primary outcome indicator. According to previous literature , the paiThe lidocaine spray -2-(diethylamino) acetamide) used in the intervention group was produced by Shanghai Xinyi Pharmaceutical Co., Ltd., a solution type, 8 g per bottle, containing 450 mg lidocaine, 4.5 mg lidocaine per spout, and 100 spouts per bottle. The spray had been approved by the China Food and Drug Administration for local anesthesia for minor operations in the mouth, nose, and throat, with a bottle of lidocaine spray costing 66 yuan RMB.The spray used in the control group was mineral water spray, which was installed in a hand-held pressurized spray tank similar in size to lidocaine spray. The mist provided a cool and comfortable feeling to the patients.Before routine skin disinfection, the water spray was applied twice at about 10 cm away from the puncture point, with an interval of 1–2 min and 3 spouts each time, and skin disinfection was performed within 1–2 min after spraying. Afterward, the standard puncture was performed according to the conventional unified and standardized operation procures: strictly disinfect; wear sterile gloves; fix the injection port with the thumb, index finger, and middle finger of the left hand; merge the two wings of the butterfly wing needle with the thumb and index finger of the right hand and hold it steady; then, insert the needle vertically, slowly, and gently; when there was a feeling of empty space, slowly insert the needle downward for about 0.5 cm, withdraw the needle, accompanied by blood returning, which confirmed that the needle reached the reservoir; immediately flush the TIVAP with 20 mL physiological saline in a pulsed manner, clamp the extension tube, separate the syringe, connect the needle-free airtight connector, and then connect the infusion device for infusion.Before routine skin disinfection, the lidocaine spray was applied twice at about 10 cm away from the puncture point, with an interval of 1–2 min, 3 spouts each time, 4.5 mg per spout, and a total amount of 27 mg. After spraying, skin disinfection was performed in 1–2 min, and then, the standard puncture was carried out according to the conventional unified and standardized procedures. The puncture method was the same as that of the control group.The two groups of patients received puncture with a 20 G non-coring needle  in the prone position. The operating nurses were all specialized intravenous therapy nurses with more than 5 years of work experience.The primary outcome measure was the patient’s pain evaluated using the visual analogue scale (VAS) of 0–100 mm from no pain to severe pain. Patients were asked to mark with a vertical line on the 100 mm horizontal scale amount of pain they experienced during the puncture: 10–30 mm mild pain, 40–60 mm moderate pain, and 70–100 mm severe pain. When using, the graduated side of the pain scale was facing away from the patient, and the patient was asked to mark the corresponding position on the scale that represented their own pain degree. The nurse gave a score based on their marked position. Compared to the verbal description scale, the VAS has proven to be more sensitive to small differences in pain intensity and pain discomfort, with higher test repeatability . Notes fThe patient was inquired whether he was willing to continue to choose this spray when conducting a non-coring needle puncture at the TIVAP in the future, and the answer options were yes, not sure, and no.The numerical rating scale  was used for assessing the self-reported comfortability of patients after maintenance: with 0 representing very uncomfortable and 10 representing very comfortable. Moreover, the numerical rating scale has also been widely used in patient comfortability assessment .The proportion of patients with successful puncture at the first time was calculated.After the puncture, a follow-up of 1 week was conducted to observe the occurrence of adverse reactions such as local skin redness, whitening, itching, and allergy.All the above indicators were designed as paper questionnaires. With the exception of adverse skin reactions observed and recorded by the quality controller, other indicators were reported by the patients themselves. The quality controller used unified guidelines to explain the requirements for completing the questionnaire and explain questions. The questionnaires were retrieved and checked for omissions or obvious logical errors.t-test; those not conforming to normal distribution were expressed as median and quartile range [M (QR)] and compared using the Mann-Whitney U test. The count data were expressed as number of cases and composition ratio [n (%)] and compared using the χ2 test. A value of P < 0.05 was indicative of statistical significance.The SPSS 21.0 software was used for statistical analysis. The measurement data were tested for normal distribution using Kolmogorov-Smirnov test, and those conforming to normal distribution were expressed as mean ± standard deviation (n=42) and the control group (n=42), as shown in Fig. P>0.05), as shown in Table The 84 patients recruited were randomly allocated to the intervention group (Table To our knowledge, this is the first study on the analgesic effect of lidocaine spray on non-coring needle puncture. We found that lidocaine spray was effective in relieving pain due to TIVAP puncture in patients, with high patient acceptance and low incidence of adverse reactions. In addition, although the median comfortability score of patients in the intervention group was the same as that of the control group, but there was a significant difference in comparison between the two groups; the successful puncture rate of the first time puncture was 100% as in the control group.Compared to conventionally used injection needles, non-coring needles contain a folding point and have a slightly longer bevel with a smaller angle, which puncture at a 90-degree angle to the injection seat with only a portion of the force acting on the needle tip, making the needle slower to pass through the skin and easily causing pain to the patient. Our results showed that the pain score of patients in the lidocaine spray intervention group was 21.38 mm lower than that in the control group, and the proportion of patients with moderate and severe pain was significantly lower than that of the control group, indicating that lidocaine spray can effectively reduce the pain caused by the non-coring needle puncture of patients implanted with TIVAP. Our results were inconsistent with the findings of Joris Datema  that theNotably, 23.8% of the patients in the intervention group still felt mild pain during non-coring needle puncture, indicating that the lidocaine spray could not completely eliminate the pain caused by the non-coring needle puncture of the patients with TIVAP. Previous studies pointed out that lidocaine spray was not enough to eliminate the pain related to venous puncture . These rAlthough the median score of comfortability for both groups of patients was 10, the difference in the comfortability score between the two groups was statistically significant. The local anesthetic effect of lidocaine spray on the skin might reduce the stimulation to the patient’s skin during disinfection and alleviate the pain of non-coring needle puncture, thus relieving anxiety and improving the comfortability of the patient. In terms of acceptance, 78.6% of patients in the intervention group reported that they were willing to choose this spray to reduce intubation pain in the future, while the acceptance in the control group was only about 28.6%, reflecting the patient satisfaction with lidocaine spray. Firstly, patients can directly benefit from lidocaine spray, that is, reducing the pain during needle puncture. Secondly, lidocaine spray can produce a mellow aroma when sprayed out. In addition, one significant advantage of lidocaine spray in pain management related to non-coring needle puncture is that it can reduce the pain of non-coring needle puncture and has no need for injection. Moreover, the effect of alleviating pain can be achieved within 5 min after the application of lidocaine spray, while local anesthetic cream and gel usually require a waiting period of at least 30 min. Hence, the use of the spray can save a lot of waiting time for patients and medical staff.In this study, only one patient in the intervention group complained of slight itching on the skin at the puncture site after the non-coring needle puncture, but it was quickly relieved. There were no other adverse reactions during the 1 week of follow-up. Many factors lead to skin itching, and it is difficult to determine whether the itching is caused by lidocaine spray. It is reported that 27.6% of patients have white skin 5 min after non-coring needle puncture with lidocaine cream for local anesthesia . CompareThis study is a randomized controlled trial that can effectively control bias and ensure study quality. However, this study is a single-center study with insufficient sample representation. To enhance the reliability of lidocaine spray in reducing needle puncture pain in cancer patients implanted with TIVAP, a multi-center study with a larger sample size is required. Moreover, this study did not assess individual pain sensitivity and pre-maintenance anxiety, which may affect the degree of individual pain. Further intervention research is warranted in the future.This study provides evidence that lidocaine spray can reduce pain caused by non-coring needle puncture at the TIVAP, which can be used for pain management related to non-coring needle puncture. However, some patients still have mild pain, and the optimal dose of lidocaine spray for pain control remains further exploration in the future.


We appreciate your comprehensive comment  on our s® programs is on the decline due to concerns about potential adverse effect, such as delaying ambulation and discharge. We agree that epidural analgesia might still have a role in certain high-risk cases, but the overall trend of ERAS® protocol seems to be moving towards alternative analgesic techniques that balance pain relief with the goal of early recovery and ambulation. At this point, our study—though retrospective in nature and in full awareness that a prospective randomized study is necessary for high-evidence conclusions—adds novel information on possible benefits of continuous wound infiltration (CWI), as there is no higher-degree evidence comparing CWI versus TEA for open nephrectomy to the best of our knowledge.According to your citation of Joshi and Kehlet, thoracic epidural analgesia (TEA) is the gold standard for major thoracic or abdominal surgery, but their recommendations for TEA on behalf of the Procedure-Specific Postoperative Pain Management (PROSPECT) working group appears to be limited . They su® International Audit System (EIAS). Unfortunately, information is pre-defined and does not contain every interesting variable for different research topics. Nevertheless, the advantage of this databank is to provide reliable data, as the information is prospectively entered by a trained and dedicated “ERAS®” nurse. Moreover, there is a constant auditing process further adding to data quality. We thank the authors for proposing a patient-centered outcome measure, which would have added valuable information. Still, by including nausea, pain scores and mobilization in our analysis, we address at least a portion of the QoR-15 items [As stated in our methodology, data of this study were retrieved from the ERAS15 items .® protocol setting, it remains, however, purely speculative that the maximal pain score corresponds to the pain score at mobilization. Concerning further effects of TEA, our results showed that the CWI group was mobilized earlier, and patients had less nausea and earlier gut mobility despite the rationale of hemodynamic assessment and visceral analgesia. Nevertheless, the retrospective design does not permit to study the causative link, but the results are similar to the randomized controlled trial investigating continuous transversus abdominal plane (TAP) block versus TEA in donor nephrectomy patients [We thank you for the opportunity to specify some issues, notably on the pain scores used. The reported pain scores in this study correspond to the maximal pain score documented, most probably during mobilization. This explains the higher pain scores in the CWI group while patients were presumably mobilized. Due to the ERASpatients . Althougmax) while using CWI devices [max was 0.71 µg/mL (SD ± 0.11 µg/mL). It is worth noting that the generally accepted threshold for neurological toxicity associated with ropivacaine is commonly cited as being around 2.2 µg/mL [max levels reached up to 3 µg/mL yet failed to induce any discernible toxicity. Particularly noteworthy among these studies is the work by Petterson and colleagues [Regarding the potential of systemic toxicity of Ropivacaine, several key points emerge from the existing literature. To begin with, the study conducted by Bianconi et al. sheds light on the peak concentration of ropivacaine , we switch to buprenorphine or fentanyl. Furthermore, to compensate for the absence of postoperative renal function in our study, we reexamined our dataset. We found that the mean creatinine value at hospital discharge was 85.7 mmol/L (SD 28.9 mmol/L). The mean GFR was calculated to be 78.9 mL/min/1.73 m2. Among these patients, only 3.1% had a severe renal impairment (GFR < 30 mL/min/1.73 m2). These values indicate a largely sufficient renal function in general for this type of surgical patient in our series. In summary, these data underscore the potential safety of CWI utilization, even in the presence of varying degrees of renal dysfunction. This serves to fortify our stance that CWI can be safely embraced in clinical practice without precipitating undue toxicity concerns.Moreover, we would like to provide reassurance that according to our local pain management protocol, strong opioid prescriptions are adapted according to renal function, though not stated in our methodology. For a glomerular filtration rate (GFR) between 30 and 60 mL/min/1.73 m® center for urology in Switzerland [As a matter of conclusion, while we acknowledge your concerns about the lack of specific details in the paper supporting the 40% overall cost reduction, we want to clarify our rationale behind this finding. The cost reduction we reported correspond to the true cost as charged to health insurance and considers the assessment of various factors including not only the differences in operating room time but also other resource-related aspects that contribute to the overall cost. While it is true that the difference in total OR time between the two groups may not appear substantial, our analysis considered all additional factors that contribute to cost reduction such as reduced nursing workload, no extensive monitoring for CWI, and reduced postoperative care. We also want to emphasize that our study took place in a specific institutional setting with established protocols and resource allocation practices. The cost reduction may be influenced by unique dynamics of our institution, to date the only true certified ERAStzerland . We valuWe hope that this clarifies our position to promote CWI and provides a better context for it. We remain committed to communicating our findings and addressing any concerns raised by reviewers.


Pain is an underappreciated symptom of atopic dermatitis that can affect the health-related quality of life (HRQL) of patients.The aim of this study is to understand the effect of pain on patients with atopic dermatitis and their family members and to recognize how this symptom affects HRQL.We conducted focus groups and interviews with patients with atopic dermatitis and their family members. Researchers independently coded the transcripts and reached a consensus on the major themes.A total of 33 adult participants, consisting of 21 patients with atopic dermatitis  and 12 family members , attended either focus groups  orinterviews , where we assessed their experiences of pain. Four themes emerged in our study. Itchiness and pain can be intertwined: pain was often caused by or otherwise associated with itchiness and could result from open sores and excoriated skin. Characteristics of pain: pain was most often described as burning. Other descriptors included mild, persistent discomfort; stinging; and stabbing. Effects of pain: pain negatively affected various aspects of daily life, including choice of clothing, sleep, social activities, and relationships. The location of painful areas could also limit physical activity, including sex. Pain management: pain from atopic dermatitis could be managed to varying degrees with different over-the-counter and prescription treatments. Systemic agents that cleared the skin also resolved the pain associated with atopic dermatitis.Pain can be a significant factor in the HRQL of patients with atopic dermatitis and should be considered by clinicians when caring for patients with atopic dermatitis. Atopic dermatitis is a chronic inflammatory skin disease with a highly symptomatic clinical course . The halSeveral studies have analyzed the effect of chronic pain on the lives of patients, highlighting the strong correlation between pain and the deterioration of health-related quality of life (HRQL) -8, and aDue to the time constraints of clinical practice, dermatologists are often unable to gain an in-depth understanding of all symptoms that the patient has and how they affect the HRQL of a patient. Dermatologists’ assessment of the frequency of primary symptoms of a patient (often itchiness with atopic dermatitis) may not accurately reflect the perspectives of the patient. For diseases in which symptoms become debilitating, the primary goal of treatment is symptom control. Failure to understand how debilitating symptoms are for patients may leave them undertreated. We aimed to document the qualitative experience of atopic dermatitis from the perspectives of patients and their families, specifically focusing on the understudied symptoms of pain with atopic dermatitis.We conducted a qualitative study using focus groups and interviews to understand the effect of pain on HRQL in patients with atopic dermatitis and their family members. Our study was approved by the University of Utah institutional review board (#98441).Participants were recruited either by recommendation from their dermatologist or by identifying patients with a diagnosis of atopic dermatitis in the electronic medical record with an upcoming appointment and having the study coordinator ask them about participating in the study at the time of the appointment. To be included, patients had to be aged ≥18 years, speak English, and have atopic dermatitis diagnosed by a University of Utah dermatologist. Family members had to be a partner or first-degree relative of a patient with atopic dermatitis, be aged ≥18 years, and speak English.We attempted to recruit a sufficiently large sample to achieve thematic saturation. In total, 21 patients and 12 family members participated in the focus groups or interviews. Each participant provided demographic data via a written survey and written informed consent before the focus group or interview. One family member also had atopic dermatitis, so they contributed data from both family member and patient perspectives.Semistructured interview guides with open-ended questions were developed regarding experiences with itchiness, pain, sleep quality, and personal relationships because of atopic dermatitis . The priInterview guide questionsPlease tell me more about the pain associated with the eczema.What words would you use to describe the pain of the eczema?Prompts: burning, stinging, pins and needles, aching, stabbing, tingling.What time of day is the eczema most painful?What are things that cause pain with eczema?Prompts: scratching too much, putting creams/lotions on your eczemaWhat helps when the pain is worst, what provides relief?How does eczema’s pain affect your sleep? The sleep of your significant other?How often is pain affecting sleep? How does it affect your bedroom relationship?How does eczema’s pain affect your mood? The mood of your loved ones?How does pain from eczema affect relationships?What other areas of your life are affected by the pain of eczema?A thematic analysis approach was used to assess transcripts ,13. Two Participants attended either focus groups  or interviews , where we assessed the experiences of 21 patients with atopic dermatitis and 12 family members. Most participants identified as female and non-Hispanic White . Four thinducing pain led to physical consequences for some, such as open sores and denuded skin:Scratching was a necessity for some patients with atopic dermatitis, and pain was sometimes an unfortunate consequence of scratching to try to relieve itchiness. The urge to provide relief from itchiness could be more powerful than the desire to avoid further consequences. This behavior of [That] is probably where the pain is coming from [...] he’s scratched it raw and then it, especially on the inner crooks of his elbows and stuff like where he’s bending them a lot, it just kind of opens those wounds back up.Conversely, scratching was not always viewed as a negative as scratching could provide relief from the pain:[Sometimes] you get the pain, but sometimes if you scratch it, now you have the sensation of scratching and now it’s not hurting like it did in that moment before the scratch. You jarred it up a little bit so your body can get a break from the pain, some relief.painful itch phenomenon experienced by some patients appeared to be a significant component of the effects of the condition. One patient explained:Itchiness and pain were sometimes difficult to distinguish from each other. This [It] doesn’t feel like it’s just itching on top of the skin; it itches down in the skin [...] if you rub it and scratch it, feels almost like a thrill going through your body but it’s a hurting thrill or [...] it’s like you’re having sex or something and you get that climax. It is like that but the only thing is it’s pain.coming from deep within, might not be stopped simply by scratching an itch. Patients in our study generally struggled with itchiness, but coexistent pain worsened daily struggles with atopic dermatitis.This pain, described as burning pain was a somewhat common description of the pain experienced:Itchiness was not always a part of the pain sensation for patients; instead, some patients felt a burning sensation that could be just as irritating. A [It’s] amazing how there aren’t any scars from it, because it’s like a fire. I mean it’s like you got burnt.One patient explained:There are times that my skin just feels like it’s on fire and there is nothing [that] will put it out.hot and burning, stabbing, dull, sharp, sunburn, sting, needle-like, or even a persistent discomfort . In addition, systemic agents could clear atopic dermatitis while also resolving the pain associated with this condition. The effects of pain from atopic dermatitis are relatively understudied but deserve further attention, both to identify the effects of pain on HRQL and to determine how to appropriately measure and potentially manage this symptom .Increased frequency and intensity of pain from atopic dermatitis leads to worse HRQL, and for some, pain can affect relationships and numerous daily activities . A studySome expressed having regained control over symptoms through medications. The use of systemic treatments, such as dupilumab, greatly improved both symptoms and HRQL outcomes for some participants, an observation supported by the literature . HoweverOne of the most challenging aspects of pain is defining it. The root cause of pain from atopic dermatitis can be difficult to identify; one study found that about 17% of patients with atopic dermatitis thought pain was part of itchiness, whereas 72% thought it was part of both scratching and itchiness . This isHelping patients express concerns and how symptoms affect their daily lives is a necessity when addressing HRQL, and we believe that appropriate methods of identifying and defining pain are needed to further address this concern with patients. One approach to measuring pain is through pain-specific patient-reported outcome (PRO) measures . PROs caOur study is limited in generalizability because it took place at a single academic medical center in a high-altitude, low-humidity environment conducive to increased atopic dermatitis severity. Expanding to other institutions and other geographic locations outside Utah may produce different results. Furthermore, our study only included adults, and thus our results might not be generalizable to the experiences of children and adolescents with atopic dermatitis. Although investigators used open-ended questions to capture the participants’ voices, it is possible that the way the questions were worded influenced participant responses. In using prompts to aid discussion, the interviewers may have directed a conversation toward those specifics, and some aspects were talked about more than others due to how questions were worded. This study is also limited in its interpretability because of its qualitative nature. Qualitative research provides an opportunity to learn about patient experiences and produce ideas for future research . HoweverThis study presents the experiences of patients and their family members in dealing with the effects of pain caused by atopic dermatitis. We found that many aspects of daily life can be affected by this symptom, and although pain can be very bothersome and significantly impact HRQL, it can be difficult for some patients to explain what they are experiencing. Clinicians must be aware that atopic dermatitis can cause pain and should ask patients about the presence and effects of pain when treating patients with atopic dermatitis.


Herpes zoster (HZ) is an infection caused by the varicella-zoster virus reactivation, often leading to peripheral nervous system infection and pain. This case report aimed to present 2 patients with damaged sensory nerves originating from the visceral neurons of the lateral horn of the spinal cord.Two patients presented intractable, severe lower back pain and abdominal pain, but without rash or herpes. A female patient was admitted 2 months after symptom onset. She was presented with paroxysmal, acupuncture-like pain in the right upper quadrant and around the umbilicus without apparent incentives. A male patient was presented with recurrent episodes of paroxysmal and spastic colic in the left waist and left middle abdomen for 3 days. Abdominal examination showed no tumors or organic lesions in their intra-abdominal tissues or organs.After excluding organic lesions on the waist and in abdominal organs, patients were diagnosed with herpetic visceral neuralgia without rash.The treatment for herpes zoster neuralgia or postherpetic neuralgia was applied for 3 to 4 weeks.Antibacterial and anti-inflammatory analgesics were not effective in either patient. The therapeutic effects of herpes zoster neuralgia or postherpetic neuralgia treatment were satisfactory.Herpetic visceral neuralgia can be easily misdiagnosed due to the absence of a rash or herpes, resulting in delayed treatment. When patients have severe, intractable pain but no rash or herpes, and the biochemical and imaging examinations are normal, the treatment method for HZ neuralgia can be used. If the treatment is effective, HZ neuralgia is diagnosed. If not, shingles neuralgia can be ruled out. Further investigations are required to elucidate the mechanisms of pathophysiological changes in varicella-zoster virus-induced peripheral HZ neuralgia or visceral neuralgia without herpes. More than 90% of the cases with HZ have a concomitant occurrence of erythema, papules, small vesicles, or blood herpes on the skin innervated with sensory nerve endings and are accompanied by spontaneous sensations of burning, pricking, cutting, electric shock, throbbing, numbness, and itching, as well as hyperalgesia.–4Herpes zoster (HZ) is an infection caused by the reactivation of the varicella-zoster virus (VZV). It commonly occurs in patients with severe diseases of the heart, lung, brain, liver, or kidney, with malignant tumors, or undergoing immunosuppressive therapy. VZV reactivation in the sensory ganglia leads to peripheral nervous system infection, which subsequently causes a band of rash and spontaneous pricking and burning sensations.Very few patients have shingles neuralgia accompanied by skin sensation or hyperalgesia but no rash. It is called rash-free shingles and can be treated as cases with shingles. However, when VZV invades the splanchnic neurons/splanchnic nerve fibers and causes pain in visceral organs, it is characterized by a wide range of pain and inaccurate localization on the body surface. As the skin sensory nerves are not involved, there is only intractable, paroxysmal colic, acupuncture, or distending pain in the chest or abdominal cavities, especially at night.In this case report, we aimed to present 2 patients with damaged sensory nerves originating from the visceral neurons of the lateral horn of the spinal cord. They showed no clinical symptoms or imaging features of visceral neuralgia, making the VZV diagnosis challenging. The treatment for HZ neuralgia was applied to the patients.Case 1: A 55-year-old female patient experienced spontaneous pricking and burning sensations and severe pain in the right upper quadrant and around the umbilicus for 2 months without obvious incentives. The Visual Analogue Scale (VAS) score was 7 to 8 at admission and was 4 to 5 in remission. The pain was more severe at night. The patient had no nausea, vomiting, acid reflux, belching, chills, fever, cough, expectoration, diarrhea, or constipation, and the urine was normal. After the onset of symptoms, the patient was treated for hepatobiliary disease and acute gastroenteritis in other hospitals. The medications included oral amoxicillin capsules for antibacterial infection, diclofenac sodium enteric-coated tablets for anti-inflammation and analgesia, and rabeprazole to inhibit gastric acid secretion; however, none of them was effective. The patient had a Pittsburgh Sleep Quality Index (PSQI) score of 17, indicating poor sleeping quality. Oral tramadol sustained-release tablets (100 mg) were ineffective when the patient had severe pain. The pain was significantly relieved 15 minutes after intramuscular injection of 100 mg of tramadol or 50 mg of pethidine, with a VAS score of 0 to 1. After each intramuscular injection of analgesics, analgesia was maintained for approximately 3 hours. Then, severe pain recurred, with a VAS score of 7 to 8. The pain could only be relieved by repetitive intramuscular injections of tramadol or pethidine hydrochloride. The patient suffered from nausea, vomiting, dizziness, and poor appetite after using analgesics. She was also distressed and depressed.After being admitted to our hospital, the patient did not develop a rash since the onset of symptoms. Physical examination showed no signs of skin erythema, rash, herpes, or skin pigmentation on the head, neck, chest, back, waist, abdomen, or limbs. There was no tenderness in the intervertebral, thoracic paravertebral, lumbar paravertebral, or thoracic intercostal spaces. The patient experienced tenderness in the right upper quadrant, the subxiphoid process, and the umbilicus. There was no paresthesia or hyperalgesia at the site of the pain. Fiberoptic gastroscopy showed that the structures of the esophagus, fundus, antrum, gastric angle, pylorus, duodenal bulb, and the descending part were normal. In the lesser curvature of the upper gastric body, a 0.3 × 0.2 cm mucosal concave and whitish structure was observed. Three polyps (0.2 × 0.1 × 0.1 cm) were also detected. There was no erosion or tumor growth in other sites. Histopathological biopsy showed moderately active gastritis in the gastric body, mucosal erosion, and inflammatory polyps. The 64-slice computed tomography (CT) with 3-dimensional imaging of the whole abdomen (including the stomach) showed no abnormality in the liver, gallbladder, stomach, pancreas, spleen, appendix, kidneys, calyces, ureter, bladder, abdominal aorta, abdominal cavity, or retroperitoneal cavity. The coagulation function was normal. The D-dimer was 0.58 µg/mL. Electrocardiogram and coronary CT angiography showed no abnormality. The blood, stool, and urine were also normal.This patient underwent gastroscopy, during which several gastric polyps were removed. However, the pain in the right upper quadrant and the subxiphoid gastric was not relieved after the operation. Multidisciplinary treatment was performed after 4 days of hospitalization. Although this patient had recurrent, spontaneous, burning, acupuncture-like paroxysmal pain for 8 weeks, laboratory examinations suggested no organic diseases in the abdomen, chest, spine, or spinal canal and no pain caused by cardiopulmonary diseases. The above examination results suggest that the visceral pain might be caused by HZ infection of the splanchnic nerve. Therefore, the treatment for shingles neuralgia was applied. The following medications were given to the patient: oral gabapentin, 300 mg/time, 3 times per day (t.i.d); pregabalin capsules, 75 mg, every night (q.n.); methylcobalamin tablets, 1.0 mg, t.i.d; vitamin B1, 20 mg, times per day (t.i.d.) Tramadol was discontinued on the treatment day. The pain was significantly relieved after 12 hours of treatment, with a VAS score of 2 and a PSQI score of 7, which significantly improved compared to those before treatment. On the second day of treatment, the VAS score was 1, and the PSQI score was 6. On the third day of treatment, the VAS score was 0 to 1, and the PSQI score was 5. After 7 days of treatment, the patient stopped taking gabapentin and pregabalin capsules. That night, she developed subxiphoid burning pain in the upper abdomen, with a VAS score of 5. The patient was immediately given 300 mg of gabapentin and 75 mg of pregabalin. The pain was significantly relieved 2 hours later, with a VAS score of 1 and a PSQI score of 5. After 2 weeks of treatment, the VAS score of the patient was 0, and the PSQI score was 3. All medications were discontinued after 3 weeks of treatment. The patient had no abdominal pain, and the sleep quality was improved. She experienced no pain during 2 months of follow-up.Case 2: A 66-year-old male patient was admitted to our hospital with recurrent episodes of paroxysmal and spastic colic in the left waist and left middle abdomen for 3 days for unknown reasons. He had a history of type 2 diabetes and took oral hypoglycemic medications to maintain fasting blood glucose levels of 6.0 to 8.0 mmol/L and glycated hemoglobin levels of 10.5%. The pain lasted 2 to 4 hours after the onset and recurred 2 hours after the relief. The VAS score was 7 to 8 when the pain occurred and was 4 when the pain was relieved. The pain severely affected the patient’s sleep quality, with a PSQI score of 17. Ureteral calculi were considered the cause of the pain at admission. The patient was given analgesics  either orally or via intramuscular injection to relieve spasms. The pain was relieved after an intramuscular injection of pethidine.Physical examination showed no signs of skin rash or herpes. There was no percussion pain in the bilateral renal regions. The entire abdomen was soft, and the mass was not palpable. The deep left lower quadrant tenderness was evident, with no rebound tenderness. There was no tenderness at McBurney point or in the right abdomen. The color Doppler ultrasound of the abdomen showed a normal liver, gallbladder, pancreas, spleen, kidneys, adrenal glands, ureters, and bladder. The blood, urine, and stool, as well as liver and kidney function, were normal. The 64-slice CT of the whole abdomen showed that the gastrointestinal tract, mesentery, appendix, retroperitoneum, abdominal aorta, inferior vena cava, intraperitoneal liver and biliary tract, pancreas, and spleen were normal. Also, there was no sign of a tumor in the abdominal cavity or intra-abdominal organs.The patient showed no rash or herpes on the body on the 6th day of admission. According to the characteristics of the pain and examination results, this patient might have herpetic visceral neuralgia. He was given the following medications: oral acyclovir tablets, 0.4 g, 4 t.i.d. for 7 days; oral gabapentin tablets, 300 mg/time, t.i.d; oral pregabalin capsules, 75 mg/time, q.n.; methylcobalamin tablets, 1.0 mg/time, t.i.d; vitamin B1, 20 mg, t.i.d. The pain was significantly relieved at night, with a VAS score of 3 and a PSQI score of 7. After 8 days of treatment, the pain was significantly relieved, with a VAS score of 1 to 2. The sleep quality was also greatly improved. After discharge, the patient continued to take gabapentin tablets , pregabalin capsules , and mecobalamin tablets . After 4 weeks of treatment, the patient stopped all medication. He was completely recovered with no obvious discomfort and high-quality sleep.,3The annual incidence of HZ is 3 to 5% worldwide, and approximately 9% to 34% of the HZ patients will develop postherpetic neuralgia (PHN). The incidence and prevalence of both HZ and PHN tend to increase with age. Therefore, HZ and PHN can be clinically diagnosed based on the pain characteristics and the appearance of rash or herpes without the results of laboratory examinations.,6 VZV is latent in the splanchnic neurons in a small group of patients after primary infection. Reactivation of VZV in patients with low resistance or damage in the splanchnic sensory nerves leads to splanchnic neuralgia, which is different from rash or herpes in peripheral sensory nerve fibers originating from the dorsal root ganglia or cranial ganglia. Visceral sensory neurons originate from the lateral horn of the spinal cord. The characteristics of visceral neuralgia and splanchnic neuralgia are different. Injuries to splanchnic nerve function may cause dull pain, referred pain, slowed gastrointestinal motility, and endocrine abnormalities, while somatic nerve injury may cause motor dysfunction and body surface pain. When VZV invades the visceral neurons and damages the sensory nerve fibers that innervate the visceral organs, intractable visceral pain may be caused. It is difficult for patients to localize the pain, which may lead to misdiagnosis and mistreatment of herpetic visceral neuralgia and postherpetic visceral neuralgia, eventually imposing a heavy economic burden on patients and resulting in a waste of medical resources.VZV is latent in the spinal dorsal root ganglia, brain ganglia, and splanchnic neurons. In most patients, reactivation of VZV results in a banded distribution of skin erythema, blisters, or pustules on the skin innervated by sensory peripheral sensory nerves. Shingles often occur on the chest, back, head, neck, face, waist, abdomen, and upper and lower limbs. They are mostly accompanied by spontaneous needle-like, knife-like, tear-like, discharge-like, hitting-like, throbbing pain, or skin hyperalgesia and numbness.3, and traditional Chinese medicine. VZV vaccination has been considered an essential preventive treatment for HZ and PHZ in the population over 50 years old. The 2 patients presented here had severe and intractable pain before diagnostic treatment. We first excluded organic lesions on the site of the pain and in adjacent tissues or organs. Then, considering the characteristics and degree of the pain, the patient’s age, and combined primary diseases, the diagnosis of herpetic visceral neuralgia or postherpetic visceral neuralgia was made. The diagnostic treatment for HZ or PHN was applied. Case 1 had been hospitalized in our hospital for over 2 months, during which no antidote was given according to the treatment plan for PHZ. Only medications for pathological neuralgia and neurotrophic drugs were used. Case 2 had a short onset time at admission. He was given antiviral drugs for 1 week and analgesics and neurotrophic drugs during the diagnostic treatment. According to our experience, treatments for HZ or PHN with typical skin rash are complex. In some patients, the treatment effect is poor in the acute phase, and the course of the disease is prolonged. The main reason is that the pathological mechanisms of neuralgia in HZ and PHN are distinct. The therapeutic effects of the treatments on our patients were satisfactory. Further investigations into the mechanisms of the treatment are warranted.Many treatments are available for patients with shingles or postherpetic neuralgia. However, the effects vary from person to person. Early treatment methods include antiviral agents, analgesics for pathological neuropathy, nutritional medicine for nerve rehabilitation, nerve block, minimally invasive nerve intervention , OIf a patient has intractable, severe pain in the chest, waist, and abdomen without rash or herpes, and the results of physical examination, routine biochemical examination, ultrasound, and CT or magnetic resonance imaging scanning are normal, the IgG and immunoglobulin M (IgM) antibodies against VZV can be detected in serum. An increase in the IgG titer and no changes in the IgM titer indicate a history of VZV infection. An increase in both IgG and IgM titers indicates recent VZV infection, which is a diagnostic criterion for herpetic visceral neuralgia or postherpetic visceral neuralgia. As the IgM titer may increase 1 to 2 weeks after VZV infection, recent VZV infection cannot be ruled out even if the IgM titer is low.The limitation of the present study is that these patients were not tested for VZV antibodies before diagnostic treatment.In conclusion, when a patient has intractable severe visceral pain but no rash or herpes, and his/her biochemical and imaging results are normal, this patient may have visceral neuralgia due to VZV infection. The levels of IgG and IgM antibodies in serum need to be measured. When the measurements for IgG and IgM titers are not available, treatments for HZ neuralgia can be applied.We thank our colleagues in the Department of Anesthesiology, Department of Emergency, and Department of Gastroenterology for their hard work and assistance.Conceptualization: Jin Zeng, Yuanyuan Yang.Data curation: Jin Zeng, Yuanyuan Yang.Formal analysis: Jin Zeng, Yuanyuan Yang.Investigation: Jin Zeng, Yuanyuan Yang.Methodology: Yuanyuan Yang.Project administration: Yuanyuan Yang.Resources: Jin Zeng, Yuanyuan Yang.Supervision: Yuanyuan Yang.Validation: Yuanyuan Yang.Visualization: Yuanyuan Yang.Writing – original draft: Jin Zeng.Writing – review & editing: Yuanyuan Yang.