Pain has become an important factor in evaluating patients' quality of life and clinical treatment. For gastric cancer (GC) patients, open radical gastrectomy (OG) causes significant trauma to the body, increases patients' pain after operation, and delays early recovery. The aim of this study was to investigate the predictive factors of acute pain after OG within postoperative 72 h.From March 2020 to September 2021, 307 patients who underwent OG were included in the study in Nanjing Drum Tower Hospital. The predictors included demographic predictors, pathological data, surgical predictors, and intraoperative predictors. The pain scores at 12, 24, 48, and 72 h after operation were evaluated by numeric rating scale (NRS). The predictors of acute pain were determined by univariate and multivariate analysis.P < 0.05), AJCC TNM stage (II) , AJCC TNM stage(III) , BMI (kg/m2) , distant metastasis , intraoperative transfusion  were significant predictive factors for acute pain after OG.The average pain score (NRS) of patients showed a downward trend over time within 72 h after OG. Multivariate analysis indicated that total gastrectomy (OR 1.823, 95% CI 1.094–3.040, Reasonable postoperative acute pain control was the prerequisite for accelerating the postoperative rehabilitation of patients. In order to reduce the occurrence of excessive or insufficient analgesia, it was necessary for patients who underwent OG to formulate appropriate analgesics according to risk factors. Gastric cancer (GC) is a common malignant tumor of the digestive system, posing a significant risk to human health. According to global cancer statistics, GC has the fifth-highest incidence rate, and was the third leading cause of cancer deaths . The onlTherefore, the study of factors affecting postoperative acute pain has important clinical significance for optimizing postoperative acute pain management . DoctorsThis study was a retrospective single-center real-world study without any intervention in the treatment. This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital, and the Ethics Committee agreed to waive the informed consent. GC patients who underwent OG at Nanjing Drum Tower Hospital from March 2020 to September 2021 were reviewed. Patients who met the following eligibility criteria were included: diagnosis of primary GC and accepted OG. All participants were Han Chinese. Patients with these conditions were excluded: remnant GC, history of other malignant tumors, quitting operation, and incomplete data.All the research predictors were from patients who were anesthetized by the same team of anesthesiologists and operated by the same team of physicians. All patients underwent general anesthesia and OG.Anesthesia information: All patients underwent total intravenous anesthesia. No premedication. The intravenous infusion pathway was established after the patient reached the operating room. Anesthesia was induced with midazolam (0.1 mg/kg), etomidate (0.2 mg/kg), cisatracurium besylate (0.4 mg/kg), and sufentanil (0.4 mg/kg). Target-controlled infusion (TCI) pump was used to maintain anesthesia with a target blood concentration of 4~6 mg/mL propofol; some patients were given patient-controlled intravenous analgesia (PCA) after surgery.All patients underwent OG. The patients were placed in the supine position as the surgical position and subjected to general anesthesia. The abdominal region of the patients was routinely disinfected. The 15–20 cm around the navel in the middle of the upper abdomen was taken as the surgical incision. The subcutaneous tissue of the patients was stripped layer by layer to expose the lesions. The anatomical position of the organs in the abdominal cavity was carefully explored. The ultrasonic knife was used to complete the operation of gastric dissociation. The operator should strictly abide by the principle of tumor-free operation. At the same time, the corresponding lymph tissue should be cleaned according to the specific position of the tumor tissue. After the operation, the bleeding was completely stopped, and the abdominal cavity was thoroughly rinsed with sterile distilled water. The incision was sutured after the operation and covered with sterile dressing. Finally, the drainage tube was placed on the abdominal wall.Postoperative patients received standard postoperative analgesia. PCA was given 10 min before the end of the operation. Fentanyl (adult: 15–20 mg/kg) was continuously infused, dexamethasone 10 mg, ondansetron 8 mg, diluted with normal saline, and the total volume was 100 ml. Dexamethasone and ondansetron prevent nausea or vomiting. The program was used for continuous infusion of background speed of 2 mL/h, a bolus dose of 0.5 mL, and lock for 15 min. Flurbiprofen axetil (50 mg b.i.d), parecoxib (40 mg b.i.d), or dezocine (10 mg b.i.d) as analgesics alleviate inflammation. If the patient complained of unbearable pain, intravenous pethidine was used as a rescue analgesic needed.Pain monitoring during hospitalization. The measurements were assessed using the American Society of Pain Guidelines for Postoperative Pain Management and the Chinese Society of Anesthesia Guidelines for Postoperative Pain Management. Pain measurement was performed at multiple time points  after the operation. The pain intensity was measured by NRS. NRS pain intensity score ranged from 0 to 10, 0 was painless, 10 was the most painful. Due to the implementation of postoperative acute pain management in our hospital, only 29.3% of patients after OG with NRS score ≥3 under the joint action of medical care and pharmacists. NRS = 3 as the cut-off value was not suitable for this study. Therefore, the NRS <2 was classified as a good analgesic effect (no pain), NRS ≥ 2 was classified as a poor analgesic effect (pain). Evaluating and recording NRS scores at multiple time points. Postoperative vomiting was recorded during follow-up. All the administrations were completed by the same postoperative acute pain management team composed of trained pharmacists.The predictors included demographic predictors, pathological data, surgical predictors, and intraoperative predictors. We collected the participants' age, gender, BMI, diabetes, hypertension, previous abdominal surgery, pre-operative hemoglobin (g/L), pre-operative albumin (g/L), carcinoembryonic antigen, and pre-operative chemo- or radio-therapy before operation. We also recorded intraoperative information, such as American Society of Anesthesiologists physical status (ASA) score, total gastrectomy, or not intraoperative blood loss (ml), intraoperative fentanyl dosage (mg), intraoperative dexmedetomidine dosage (mg), and duration of operation (min). According to postoperative pathological data, we recorded tumor location, tumor size (cm), Lauren's histology, pathological grading, lymph node metastasis, depth of invasion, distant metastasis, lymphovascular invasion, and perineural invasion. Pathologic staging was evaluated according to the 8th American Joint Committee on Cancer (AJCC) staging system of GC.IBM SPSS Statistics software  was used for statistical analysis. All continuous predictors were expressed by mean ± SD or median and quartiles . All classification predictors were represented by percentages.t test or Mann- Whitney U test was used for univariate analysis to evaluate the related factors of patients. Categorical predictors were analyzed using the chi-squared test. In order to determine the risk factors for predicting poor analgesic effect, binary logistic regression was performed for multivariate analysis. Values of P < 0.05 were considered statistically significant.According to the distribution characteristics of data, Student A total of 354 patients were close to participate in this study. 15 patients with gastric stump cancer, 10 patients who abandoned surgery, 14 patients with other malignant tumor histories, and 8 patients who had incomplete data were excluded from the study. Therefore, 307 patients were available for analysis .Demographics information, underlying diseases, data on surgery, and ASA classification were collected by researchers. Descriptive statistics for the patient characteristics are presented in P < 0.05), and AJCC TNM stage (P < 0.05) was related to postoperative acute pain after OG. At postoperative 48 h, BMI (P < 0.01), diabetes (P < 0.05), hypertension (P < 0.05), Lauren's histology (P < 0.05), intraoperative blood loss (P < 0.05), and duration of operation (P < 0.05) were related to postoperative acute pain. At postoperative 72 h, BMI (P < 0.05), diabetes (P < 0.05), pre-operative hemoglobin (P < 0.05), intraoperative blood transfusion (P < 0.01) were related to postoperative acute pain. BMI and diabetes were both associated with postoperative acute pain at 48 and 72 h. In addition, there was a difference in the patient sources between groups, but this difference did not reach statistical significance. We used these predictors in the multivariate analysis.Our study assessed the pain scores at 24, 48, and 72 h after surgery. P < 0.05) in the univariate analysis (P < 0.05), AJCC TNM stage (II) , and AJCC TNM stage (III) . After operation 48 h, the significant predictors included BMI (kg/m2) . After operation 72 h, the significant predictors included distant metastasis , intraoperative transfusion .To determine the risk factors of pain after OG, binary logistic regression was used to investigate the predictors that showed a significant difference . Binary logistic regression analysis used backward conditional, eliminated non-local variables step by step, and finally got 5 significant predictive factors (P < 0.05). It could not only explain the correlation between variables and postoperative acute pain after OG, but also reflect the strength of the correlation through OR value. In this study, total gastrectomy, AJCC TNM stage (I), BMI≥21 kg/m2, distant metastasis, intraoperative blood transfusion (≥100 ml) were risk factors for postoperative acute pain.To determine independent predictors of pain after OG within 72 h, we used binary logistic regression models after univariate analysis. There were so many variables included in this study, including demographics information, pathological data, and surgical data. Univariate analysis was carried out to screen out some variables which may be meaningful. And then binary logistic regression analysis was performed on variables with differences (N-methyl-D-aspartic acid (NMDA). These receptors specifically recognized the corresponding inflammatory mediators, enhancing the excitability nerve fibers, and improving the sensitivity of injury receptors to injurious stimuli  after OG. Most studies from Asian Centers used BMI value of 25 kg/m2 as the critical value for dividing patients into obesity, which was inconsistent with the current definition of obesity by the WHO  level  could predict the long-term prognosis of radical gastrectomy . Saito eAccording to the 8th AJCC TNM classification system, no matter the depth of tumor penetrating the gastric wall (T) and the number and state of lymph nodes (N), distant metastasis is divided into stage IV. Patients at the IV stage usually suffer from a long and painful illness. Postoperative patients in our hospital would use non-steroidal anti-inflammatory drugs combined with opioids analgesia. Opioids play an analgesic effect by simulating the physiological role of endogenous opioid peptides . PatientIn our study, blood transfusion was an independent predictor of postoperative acute pain. Blood transfusion could save a life in many cases but had a negative influence on immune regulation, postoperative infection, and tumor metastasis, and recurrence . ImmunomOur study also had some limitations. We only evaluated and explored the possible factors affecting pain within 72 h after surgery. There was no study on the influencing factors of pain 3 days and long-term after surgery. At the same time, our research was limited to OG, and there was no study on the influencing factors of pain after LRG and robotic radical gastrectomy for GC. In addition, postoperative acute pain was affected by genetic polymorphism related to pharmacokinetics, pharmacodynamics of analgesics  and psycPain has become an important factor in evaluating patients' quality of life and clinical treatment. Medical staff should predict the influencing factors of postoperative acute pain, formulate reasonable analgesic schemes, and reduce the occurrence of excessive analgesia and insufficient analgesia. Reasonable postoperative pain control was the prerequisite for accelerating the postoperative rehabilitation of patients.2), distant metastasis, and intraoperative transfusion (≥100 ml) were significantly associated with pain after OG within postoperative 72 h. To reduce the occurrence of excessive analgesia and insufficient analgesia, formulating appropriate analgesics according to these risk factors was necessary for patients who underwent OG.Total gastrectomy, AJCC TNM stage (I), BMI  and Special Fund for Clinical Research of Nanjing Drum Tower Hospital (No. 2021-LCYJ-PY-07). HX was responsible for the overall content of these funding as guarantor. The guarantor accepted full responsibility for the finished work and the conduct of the study, had access to the data, and controlled the decision to publish.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients with lung cancer. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. In this study, we aimed to assess the effect of transcutaneous electrical nerve stimulation (TENS) therapy on the pain intensity and the quality of life of patients with cisplatin-induced neuropathy. Material and Methods: A prospective cohort study was performed from 2013 to 2018, at the Clinical Center of Serbia. After the initial evaluation of 106 newly diagnosed patients with lung cancer, 68 patients did not have peripheral neuropathy. These 68 patients continued in the study and started the cisplatin chemotherapy. Forty of these patients developed cisplatin-induced neuropathy, which was manifested by neuropathic symptoms and proven by ENG examination. All patients with cisplatin-induced neuropathy were treated with TENS therapy. Their neuropathic pain and quality of life were evaluated using the following questionnaires at diagnosis, after cisplatin therapy and after four weeks of TENS use: DN4, VAS scale, EORTC QLQ-C30 and FACT-L. Results: Two thirds (68%) of the patients with cisplatin-induced neuropathy were male and the majority were smokers (70%). Adenocarcinoma was the most common (38%), followed by squamous (33%) and small-cell carcinoma (28%). The application of TENS therapy had a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy. The VAS and DN4 scores significantly decreased after TENS therapy, in comparison to its values after cisplatin therapy (p < 0.001). After TENS therapy, patients had significantly higher values in most of the domains of EORTC QLQ-C30 and FACT- L, in comparison with the values after cisplatin therapy (p < 0.001). Conclusion: The application of TENS therapy has a positive effect on reducing neuropathic pain and increasing the quality of life for patients with lung cancer and cisplatin-induced neuropathy. Lung cancer is the second leading malignant disease in the world. It is estimated that approximately 2.2 million new cases of lung cancer are diagnosed annually. Lung cancer is the most common cause of death from malignant tumors in men, and, after breast and colorectal cancer, it is the leading cause of death from malignant tumors among women . Neurolo2. At a cumulative dose of 500 to 600 mg/m2, almost all patients have objective evidence of neuropathy. However, a significant inter-individual variation persists as a consequence of the genetic polymorphisms of the enzymes related to cisplatin metabolism . A greater intensity of the cisplatin dose per unit of time does not affect the severity of neuropathy [Cisplatin-induced peripheral neuropathy is a common complication of cisplatin therapy, which develops in most patients. There are no effective preventive measures and once it occurs there is no effective therapy, except symptomatic. Cisplatin causes axonal neuropathy that predominantly affects large myelinated sensory fibers. The primary site of damage is the dorsal root ganglia, but peripheral nerves can also be affected. Unlike the central nervous system, the peripheral nervous system does not have a blood–brain barrier, and, therefore, allows contact with chemotherapeutics and other neurotoxins. The lack of the lymphatic system and cerebrospinal fluid surrounding the peripheral nerves allows harmful substances to build up around the nerve tissue, worsening the neuropathic damage . Cisplaturopathy ,8.When a mild neuropathy occurs, the continuation of therapy at the full dose is recommended. In the case of more severe neuropathy, a change in the therapy is considered, e.g., replacement of cisplatin with carboplatin. Even when cisplatin is stopped, in 30% of patients the symptoms of neuropathy worsen over the following months. Patients usually experience coldness, tingling, itching, burning, numbness and pain. Moreover, symptoms can be so intense that they are perceived as electric shocks or burns, which worsen when a part of the patient’s body in which neuropathic symptoms are present is touched ,10. The Some patients improve over time, although only partially ,15. The The study was conducted from December 2013 to January 2018 at the Clinic of Pulmonology, the Clinic of Physical Medicine and Rehabilitation and the Clinic of Neurology at the University Clinical Center of Serbia. The research protocol was approved by the Ethics Committee of the Clinical Center of Serbia, and written informed consent was obtained from each patient. The inclusion criteria were as follows: newly diagnosed histopathologically confirmed lung cancer, ECOG performance status ≤ 3 and patients over 18 years of age. Patients with any intoxication (ethylic etiology or elevated blood sugar levels), diabetes, increased levels of nitrogen substances in renal failure, increased levels of thyroid hormone in hyperthyroidism, associated systemic diseases, sarcoidosis, hematological diseases, hepatitis, HIV, previous radiotherapy, trauma or surgical intervention (up to 6 months), vitamin B12 deficiency and gammopathy were excluded from the study.The initial evaluation of 106 newly diagnosed patients with lung cancer showed that 68 patients did not have peripheral neuropathy . They coThe following tests and questionnaires were used in the study:Sociodemographic questionnaire. The following sociodemographic characteristics were assessed: gender, age, smoking habits , cancer stage and histopathology.Neurological symptom survey. Neurological symptom survey consisted of 26 questions assessing the presence of unilateral or bilateral sensory and/or motor neurological symptoms on the upper and lower extremities. Possible answers were “yes” or “no”, and the presence of bilateral neurological symptoms suggested the diagnosis of neuropathy.Medical Research Council (MRC) sum score. MRC sum score is a quantitative muscle strength assessment tool used to assess the strength of the muscles of the upper and lower extremities. The assessment of the gross muscle strength of the muscles is conducted bilaterally, whereby the ranking is from 0 (absence of movement) to 5 . The sum score ranges from 0  to 80  [muscles) .Douler Neuropathique in 4 questions (DN4). DN4 is a survey questionnaire that consists of two parts and is used in the diagnosis of neuropathic pain. In the first part, patients were interviewed using two questions, with 7 items that describe the quality of pain and sensitive symptoms felt by the patient. The second part was based on a clinical examination and had two questions with 3 items that examined a reduced sensation to touch or needle prick (hypesthesia) and whether pain increased or appeared when the brush was lightly pressed over the skin . All affirmative answers were scored with one point, and all negative answers were scored with 0 points. The results were added up and a score ≥ 4 indicated pain of neuropathic origin [c origin .Electrophysiological examination (ENG). Peripheral nerve conduction studies, both conventional and standardized, were performed bilaterally for the upper (median and ulnar nerves) and lower extremities , using surface stimulation electrodes, and with the registration of evoked responses using the Sinergy EMG device . The filter settings were 3 Hz–10 kHz for motor conduction studies and 20 Hz–2 kHz for sensory conduction studies. The filters for the F-wave were set between 30 Hz–10 kHz, with the application of the built-in notch filter (50/60 Hz) function in the EMG machine. During stimulation and monitoring, the following electrophysiological indicators were recorded and then analyzed: compound muscle action potentials (CMAPs) in the m. abductor pollicis brevis, m. abductor digiti minimi, m. extensor diggitorum brevis and m. flexor hallucis brevis. Furthermore, distal and proximal muscle latencies, motor nerve conduction velocity (MNCV) and late latencies response (LLR) were recorded for the same CMAPs. Sensory nerve action potentials (SNAPs) were examined with antidromic stimulation for the median, ulnar and sural nerves bilaterally, using ring electrodes on the 2nd and 5th fingers for the median and ulnar nerves, as well as on the big toe for the sural nerve. MNCVs were registered between the wrist and the cubital fossa (for the median nerve); the wrist and the elbow (for the ulnar nerve); the ankle joint  and the popliteal fossa ; and between the ankle joint and the proximal position below the head of the fibular bone . The sensory nerve conduction velocities were calculated for the distal segments of the extremity using the antidromic method. Amplitudes of the CMAPs and SNAPs were measured from the initial deflection (deviation from the isoelectric line) to the first negative peak. Lower reference limits were defined as mean values, reduced by two standard deviations in relation to the normative data of the laboratory, registered in the same way. For each nerve, we defined typical electrophysiological patterns of abnormalities, as follows: demyelinating pattern, axonal pattern, and combined axonal/demyelinating damage pattern. The presence of abnormalities in at least two peripheral nerves was considered as electrophysiological impairment.Visual Analogue Scale (VAS). VAS scale is an instrument used to measure the subjective feeling of pain intensity. It is designed as a horizontal line, containing indicators for the absence of pain, through medium intensity to the maximum sensation of pain. The patient marks their perception of pain at that moment, at a certain point on the scale. The numerical value of pain corresponds to the patient’s subjective feeling of pain [ of pain .Questionnaire on assessment of quality of life of patients suffering from malignant disease (EORTC QLQ-C30). EORTC QLQ-C30 is a questionnaire used to assess the quality of life in patients with a malignant disease [ disease . The queQuestionnaire for assessing the quality of life of patients undergoing lung cancer therapy (FACT-L). FACT-L is used for the assessment of the quality of life in patients undergoing therapy for lung cancer [g cancer . The queTENS use. All patients with cisplatin-induced neuropathy were treated with TENS for 4 weeks, 5 days a week and each session lasted 30 min. No patient underwent TENS more than once a day during the study. The characteristics of electrical currents used were as follows: 2 channels, 4 outputs, pulse frequency 80 Hz/s, pulse duration 200 µs, and electric current strength approximately 60 mA. The electric current strength was adjusted according to the patients’ subjective feelings, until the feeling of tingling without pain or discomfort was felt. TENS electrodes were positioned diagonally, with the center in the zone of pain, so that electric current passed through the target zone. The patients felt a pleasant tingling sensation that masked the sensation of pain. During the study period, patients did not receive gabapentinoids or any analgesic drug therapy for neuropathic pain.Statistical analysis. Baseline characteristics and sociodemographic data were stratified by the presence of neuropathy in patients, as well as the diagnosis of neuropathy before and after cisplatin therapy. Numerical data were presented as mean, with 95% confidence interval, or with minimum and maximum value. Categorical variables were summarized as absolute numbers with percentages. Changes in examined variables from baseline (time at diagnosis) to after cisplatin and after TENS therapy were evaluated by repeated measures ANOVA. Interactive line graphs for presenting changes during time in examined variables were created using an interactive graph tool [aph tool . In all aph tool .A total of 106 patients with newly diagnosed lung cancer were initially included in the study. The majority were male, with a mean age of 64 (47–83) years. Most patients were diagnosed with the third stage of the disease (53%), a squamous type of lung cancer (37%) and a non-small-cell carcinoma (70%). The characteristics of the patients without and with neuropathy on initial evaluation are shown in Out of 106 patients with lung cancer, 38 had neuropathy at the time of diagnosis and were excluded from further evaluation. After four months, 40 patients developed cisplatin-induced neuropathy. Two thirds of the patients with cisplatin-induced neuropathy were male (68%). The youngest patient was 47 years old, while the oldest was 82 years old. The majority of the patients with lung cancer and cisplatin-induced neuropathy were smokers (70%). Adenocarcinoma was the most common type of lung cancer in patents with cisplatin-induced neuropathy (38%), followed by squamous (33%) and small-cell carcinoma (28%) .All patients with cisplatin-induced neuropathy underwent TENS therapy for their neuropathic pain, and their quality of life, using different questionnaires, was measured at diagnosis, after cisplatin therapy and after TENS therapy.In The EORTC QLQ-C30 questionnaire and its domains were evaluated at the time of diagnosis, after cisplatin therapy and after TENS therapy, and the results are presented in p < 0.001). In comparison to the VAS score after cisplatin therapy, the value of the score significantly decreased after TENS therapy (p < 0.001).The value of the VAS score changed during the follow up . The VASp < 0.001).The neuropathic pain in the patients, measured using DN4 questionnaire, was at its highest level after cisplatin therapy . After aWe performed a prospective cohort study to assess the effects of TENS therapy on patients with cisplatin-induced neuropathy and concluded that the application of TENS therapy has a positive effect on reducing the neuropathic pain and increasing the quality of life for patients with painful cisplatin-induced neuropathy.The etiology of neuropathies in malignant patients is considered to be multifactorial, including the metabolic and nutritional deficits, but also including unrecognized factors, which typically appear in the advanced stage of the underlying disease ,29. The Patients with lung cancer often develop chemotherapy side effects that can impair further therapy implementation. Previously published studies reported that 30% of peripheral neuropathies are due to the neurotoxicity of oncological drugs ,34,35.n = 31), case series (n = 30) and 10 retrospective studies. One hundred and forty-two cases of lung cancer were associated with neurological symptoms and diagnosed as sensory neuropathy [2 and that, with a cumulative dose of 500 to 600 mg/m2, almost all of the patients had objective evidence of neuropathy [2 cisplatin.Differentiating acquired sensory neuropathies from other neuropathies is important for the selection of adequate therapy. The systematic literature review published by Ruelle et al. in 2017, included case reports . The peripheral neuropathic pain group (PNP) showed more complete improvements than the central neuropathic pain group (CNP). The mean pain intensity in the PNP group was reduced by 38%, and in the CNP group by 15%. Studies have reported that improvements in terms of pain reduction are significant when the improvement is greater than 30% [Although a large number of cancer patients develop chemotherapy-induced neuropathy, there is still insufficient data in the literature regarding the use of TENS for the treatment of neuropathic pain in this patient population. Studies have been conducted in patients with diabetic polyneuropathy, peripheral mononeuropathy of traumatic origin, in painful cervical radiculopathy, and in patients with chronic pain that includes a neuropathic component ,44,45,46than 30% . The resthan 30% . An incrthan 30% ,49,50.p < 0.001). The effectiveness of TENS therapy was also confirmed in our study by measuring the VAS score. The value of the VAS significantly decreased, from a mean value of 4.3, to one of 3.0 after TENS therapy. Additionally, most of the domains of the EORTC QLQ C30 questionnaire showed significant improvement in the quality of life for our study group after TENS therapy.A study by Siemens, published in 2020, evaluated the efficacy and safety of TENS therapy as an additional therapy for cancer patients. To assess the patients’ quality of life, the EORTC QLQ C30 questionnaire was used in a placebo and intervention group, as well as the DN4 for the assessment of neuropathic pain. Their results imply that TENS therapy is a safe treatment method but the difference in the analgesic effect between the intervention and the placebo group was not significant . AccordiFiorelli et al. reported that TENS treatment created a greater reduction in the postoperative pain intensity of lung cancer patients who had undergone a thoracotomy, than it had in the placebo group . FereiraIn a study by De Santana et al., high and low frequency TENS therapy was used for a reduction in postoperative pain. One group was treated with 100 Hz (high), the second with 4 Hz (low) frequency, and the third group with a placebo. TENS therapy was applied for 20 min, at a pulse duration of 100 ms. Electrodes were placed around the incision. The pain intensity was measured by the numeric rating scale. The pain was significantly reduced, in comparison to the placebo group, immediately after the TENS treatment . To attaThe mixed results of TENS therapy’s effectiveness for reducing neuropathic pain presented in the literature can be explained by the differently applied duration of the TENS therapy, as well as by the variations in the TENS pulse widths, rates, frequencies and electrode site positions. Establishing field-wide methodological and analytical standards may allow researchers to gain additional insights into the role of TENS therapy in reducing pain for patients with lung cancer and cisplatin-induced neuropathy.This study has some limitations. These include the small sample size, having patients recruited from a single center and the absence of a control group. In addition, the fact that we did not monitor the long-term effects (beyond more than 4 weeks) of TENS therapy in reducing the patients’ neuropathic pain can be considered as another limitation of the study and an opportunity for future research. Further studies investigating the use of TENS therapy in patients with chemotherapy-induced neuropathy are needed in order to confirm the results obtained in our study.The findings of this study support the role of TENS therapy in reducing neuropathic pain and in improving the quality of life for patients with lung cancer and cisplatin-induced neuropathy.


Digital therapeutics are growing as a solution to manage pain for patients; yet, they are underused in primary care where over half of the patients with chronic pain seek care. Little is known about how to successfully engage primary care providers in recommending digital therapeutics to their patients. Exploring provider motivations in chronic pain management would potentially help to improve their engagement and inform the development of digital therapeutics.This study examined primary care providers’ motivations for chronic pain management, including their strategies and challenges, to inform the future development of chronic pain-related digital therapeutics tailored to primary care settings.We conducted qualitative semistructured interviews with health care providers recruited from 3 primary care clinics in Washington and 1 clinic in Colorado between July and October 2021. The sample (N=11) included 7 primary care physicians, 2 behavioral health providers, 1 physician assistant, and 1 nurse. Most providers worked in clinics affiliated with urban academic health systems. Guided by the human-centered design approach and Christensen’s Job-to-be-Done framework, we asked providers their goals and priorities in chronic pain management, their experiences with challenges and strategies used to care for patients, and their perceptions of applying digital therapeutics in clinical practice. Transcripts were analyzed using a thematic analysis approach.We found that primary care providers were motivated but challenged to strengthen the patient-provider alliance, provide team-based care, track and monitor patients’ progress, and address social determinants of health in chronic pain management. Specifically, providers desired additional resources to improve patient-centered communication, pain education and counseling, and goal setting with patients. Providers also requested greater accessibility to multidisciplinary care team consultations and nonpharmacological pain treatments. When managing chronic pain at the population level, providers need infrastructure and systems to systematically track and monitor patients’ pain and provide wraparound health and social services for underserved patients. Recommendations on digital therapeutic features that might address provider challenges in achieving these motivations were discussed.Given the findings, to engage primary care providers, digital therapeutics for chronic pain management need to strengthen the patient-provider alliance, increase access to nonpharmacological treatment options, support population health tracking and management, and provide equitable reach. Leveraging digital therapeutics in a feasible, appropriate, and acceptable way to aid primary care providers in chronic pain management may require multimodal features that address provider motivations at an individual care and clinic or system level. Chronic pain is defined as persistent or recurrent pain for 3 or more months . About 2As pharmacologic treatments of pain have limited efficacy and potential side effects and harms, most chronic pain guidelines include nonpharmacologic and complementary therapies to treat and manage chronic pain . EvidencDigital therapeutics, evidence-based high-quality software products that deliver therapeutic interventions to treat, manage, and prevent a broad spectrum of diseases , are groA human-centered design approach, which grounds the development of any innovations, technologies, and products based on the needs of the people and the settings in which they will use it, was used to develop the study . The goaWe recruited physicians, nurses, physician assistants, and behavioral health providers, who work in primary care clinics and have treated patients with chronic noncancer pain. We used convenience and snowball sampling for the recruitment of participants within the WWAMI  region Practice and Research Network (WPRN), a regional primary care practice-based research network, and among primary care providers with whom study team members collaborated with in the past. Study outreach focused on recruiting a broad range of provider specialties and roles within primary care clinics and a breadth of practice types and locations. Providers including 10 clinic champions from 11 clinics located in Washington, Idaho, Alaska, Montana, Kansas, and Colorado were invited to participate via email and asked to recruit other providers within their clinics and professional networks. These clinics represented a mix of urban or rural serving, residency training, and nontraining sites. We were not able to collect data on the total number of invitations that were subsequently sent by initial invitees, but everyone who agreed to participate completed their interviews. This study followed the Consolidated Criteria for Reporting Qualitative Research guideline .The study was approved by the University of Washington Human Subjects Division (#STUDY00012442). Participants provided informed consent prior to their interviews. To protect participants’ confidentiality, no direct identifiers were used in the interviews and the participants were assigned with subject codes. Participants received a US $100 gift card for their participation in the study.Semistructured interviews with providers in primary care were conducted remotely between July and October 2021. The interview guide see  was deveTranscripts were coded using Dedoose   and analWe completed individual interviews with 11 providers from 4 primary care clinics in Washington and Colorado see . Most prParticipants shared numerous experiences of strategies and challenges when caring for patients with chronic pain. Using the Job-to-be-Done theoretical framework , we summProviders believed that the patient-provider alliance in chronic pain management requires empathizing with patients about their lived experiences, eliciting patients’ goals, and providing education on chronic pain and treatment options. A participant said:The first part is just trying to understand what they enjoy doing. [...] to see if I can find out what they like. Then, when did they last do that, what have been some of the barriers that they can think of, and then just talking about the cycle of psychoeducation about what happens with depression [...] Just try to validate that, even though it's seemingly simple, it's one of the hardest things in the world to get started doing something.Behavioral health providerSome providers took notes about patients’ personal details  as reminders for future visit discussions. Other providers asked patients their favorite pastime that they have avoided due to pain and found ways to help patients re-engage in activities that are meaningful to them. Providers emphasized the importance of educating patients on the biological, psychological, and social components of pain and the variety of treatment options that are evidence-based, safe, and appropriate to patients. These conversations discussed the benefits and risks of pharmacological treatments and normalized nonpharmacological treatments.What providers found challenging was the brevity of 15- to 20-minute appointments that typically did not allow them to do all of the things mentioned above and to gain trust and mutual understanding with patients. Providers felt pressured to see a high volume of patients, which made conversations with patients about their lives, goals, and treatment plans difficult to achieve.Providers reported lacking the time, skills, and resources needed to process patients’ distress and repair their alliance when there is misalignment between patients and their expectations. A participant described it this way:[The health system] wants me to be productive as a PCP and see so many patients per day, which limits the amount of time that I can spend per visit with each patient. So having adequate time to provide this education, to sit and to listen to the tears and the fear, and then try to manage that with the patient in a patient centered, compassionate way is hard. So, time is a big issue.Primary care providerProviders relayed that they occasionally feel conflicted about maintaining boundaries with opiate prescribing  when time constraints do not allow for comprehensive education and realistic goal-setting conversations with patients for a shared decision-making process.Considering the complexities of chronic pain diagnosis and management, primary care providers relied on support from pain specialists, physical therapists, behavioral health providers, and pharmacists. Providers described seeking consultations from multidisciplinary team members for diagnostic clarification and ideas on managing patient’s pain. In addition, they referred patients to work with certain specialists for specific treatment goals in order to provide whole person care. Primary care providers noted that their ability to use multidisciplinary team support was limited by the availability of in-clinic consulting specialists and structured time for consultation. Only a few providers reported access to social work, behavioral health, and pharmacy services in their clinics. One participant mentioned that their clinic used to have allotted time for in-person consultation with a pain specialist on a monthly basis:We had a pain consult guy come to [clinic] for a while. He would come about once a month, and it was a set thing on the schedule. The front desk would often try to schedule your chronic pain patients for that spot. He really thought of all the angles, he was a nice resource to have, but that's not a thing anymore, I don't know what happened with that.Nurse practitionerProviders desired regular interdisciplinary team meetings to review complex cases and gain new perspectives and suggestions on how to support their patients.Multiple providers raised concerns about the lack of standardized clinic processes and structures in identifying, tracking, and monitoring patients’ progress along a care trajectory. Providers shared that they relied on patients to self-monitor their pain symptoms, changes in activity, and factors impacting those changes over time. A participant said:Ideally, I use scales. I have done that in the past, but in practicality that doesn’t always happen, doesn’t always fit in. So a lot of it’s just kind of freeform conversationPrimary care providerSome providers mentioned they had experiences recommending mobile apps to patients for tracking and self-monitoring health conditions such as blood pressure, glucose levels, and menstrual cycles and used the data for follow-up visits; however, none of them knew about apps specific for chronic pain. Few providers also expressed their concerns about how to educate patients to use apps for self-monitoring. Rarely did providers use standardized assessments for pain in visits because they think pain conversations needed to be tailored to each patient. However, at the population level, providers were aware of the potential pitfalls of not tracking patients’ symptoms in a standardized way.In addition, providers said there were no support structures or streamlined processes in the clinics to coordinate follow-up care for patients with chronic pain. Many providers developed “workaround” solutions to track patients’ appointments and remind themselves of scheduling follow-up visits with patients. For instance, some providers described scheduling patients themselves for follow-up at the end of a visit or providing a direct hand-off to the schedulers with instructions on the timeframe for the patient’s next visit. Other providers manually reviewed their patient panels from time to time and reached out to patients who missed appointments or required follow-up. The nurse practitioner said:I have an inbox, and I keep things there if there's results or a person that I want to follow up on, or I don’t want to forget about. I will go through that every once in a while.Although the process of monitoring and tracking patients and visits was individualized to provider preferences, providers considered this to be time-consuming and burdensome for themselves and the patients, and left much room for compromising patients’ care. Providers added that the electronic health record (EHR) systems were not user-friendly to providers for documentation and tracking, which further complicated their panel management.Providers considered the overall impact of social determinants of health on the chronic pain experience for patients. As part of treatment planning, almost all providers inquired about potential factors and barriers that impact patients’ access to care. Once barriers were determined, providers reached out to other clinic members and the patient’s support system  to find ways to address the barriers. For instance, a provider shared they connected patients with in-clinic social workers for referrals to community resources meeting basic needs. Another provider sought interpreter services for multilingual patients to overcome language barriers during treatment. Despite the initiatives, providers recognized some social and systemic barriers remain persistent and difficult to address. Providers specified the lack of health insurance coverage and access to reliable transportation as common barriers for patients in accessing nonpharmacological treatments. A participant said:Then also sustainability, like how realistic is this practice for this patient. Especially at [clinic] a lot of our patients don't have access to adjunct chronic pain things like acupuncture, or even getting to physical therapy, or swimming, or things like that. So really kind of considering the socioeconomic status and resources [of] that patient.Physician assistantThey also mentioned factors like being unhoused and inadequate access to nutritious foods exacerbate chronic pain and delay treatment. When the idea of using digital technologies to augment care was discussed, some providers raised concerns about the inequitable access of these technologies for underserved patients, including those who speak a primary language other than English, have low digital literacy, and have unstable internet access.Drawing upon providers’ reported experiences of strategies and challenges, this qualitative, human-centered design study revealed provider motivations in chronic pain management that would have implications to the development of digital therapeutics tailored to primary care settings. We found that primary care providers were motivated to (1) strengthen patient-provider alliance, (2) provide team-based care, (3) track and monitor patient’s progress, and (4) address social determinants of health in chronic pain management. Specifically, providers desired additional resources to improve patient-centered communication, pain education and counseling, and goal setting with patients. Providers also requested greater accessibility to multidisciplinary care team consultations and nonpharmacological pain treatments. When managing chronic pain at the population level, providers need infrastructure and systems to systematically track and monitor patients’ pain and provide wraparound health and social services for underserved patients. Given these findings, this study underscored the importance of designing digital therapeutics that would engage and support primary care providers in overcoming challenges to fulfill their various motivations when caring for patients with chronic pain. Below, we offer 4 digital therapeutic feature areas supported by the findings and literature that might address provider challenges in meeting those motivations.First, patient-provider alliances can be strengthened through the inclusion of patient-generated data and the development of communication interfaces in digital therapeutics . The incSecond, digital therapeutics that integrate seamlessly with care delivery systems are crucial to population health management for chronic pain ,38. Our Third, the emerging evidence on digital therapeutics that are developed using evidence-based behavioral interventions for chronic pain could be a promising alternative to providing patients with more support and treatment options, especially when a shortage of pain specialists and health care workers who deliver nonpharmacological pain treatments limit access to care ,18,19,22Fourth, our findings suggested that chronic pain is complicated by social determinants of health, and reducing disparities in access to care for under-resourced populations is a top concern for primary care providers. One study has demonstrated the feasibility of mobile apps and fitness trackers to engage disadvantaged and multilingual patients to collect patient-generated data that can be integrated into the EHR to improve chronic disease management in primary care . AlthougIn addition to designing features that could meet providers’ motivations, special attention should also be given to the implementation of digital therapeutics in health care systems. Prior studies have suggested possible logistical and workflow challenges, such as training providers to use digital apps with patients in clinical visits, creating a workflow to assist patients in enrolling and setting up digital app programs, and designating personnel and time to review patient-generated data from the digital therapeutics ,45. ThesDespite our outreach attempts, multiple challenges arose for health care providers to participate in research during the COVID-19 pandemic. Many providers who were unable to participate in the study responded that the reasons for their inability to participate included a lack of time due to clinical duties from COVID-19, provider shortages in their clinics, and other competing priorities. The small sample size of 11 participants who were recruited from 4 clinics in urban and academic health systems in the states of Washington and Colorado may not be generalizable to all primary care providers, and there might be bias in participants who volunteered to join the study. Also, many of our participants were female, non-Hispanic, and middle-aged—provider characteristics that have shown influences on some pain management decisions and opioid-prescribing patterns ,46. NeveBased on our findings, to engage primary care providers, digital therapeutics for chronic pain management need to support and strengthen the patient-provider alliance, team-based care, systematic tracking and monitoring, and addressing social determinants of health. Leveraging digital therapeutics in a feasible, appropriate, and acceptable way to aid primary care providers in chronic pain management may require multimodal features that address provider motivations at an individual care and clinic or system level.


N-palmitoylethanolamine (PEA), N-oleoylethanolamine (OEA), and their endogenous precursor and breakdown product, arachidonic acid (AA), were analyzed using liquid chromatography/tandem mass spectrometry in 83 chronic OFP patients and 43 pain-free controls. The chronic OFP patients were divided according to diagnosis into musculoskeletal, neurovascular/migraine, and neuropathic pain types. Results: chronic OFP patients had lower levels of OEA (p = 0.02) and 2-AG (p = 0.01). Analyzing specific pain types revealed lower levels of AEA and OEA in the neurovascular group , and 2-AG in the neuropathic group compared to controls (p = 0.05). No significant differences were found between the musculoskeletal pain group and controls. Higher pain intensity was accompanied by lower levels of AA (p = 0.028), in neuropathic group. Conclusions: lower levels of eCBs were found in the saliva of chronic OFP patients compared to controls, specifically those with neurovascular/migraine, and neuropathic pain. The detection of changes in salivary endocannabinoids levels related to OFP adds a new dimension to our understanding of OFP mechanisms, and may have diagnostic as well as therapeutic implications for pain.Background: the endocannabinoid system (ECS) participates in many physiological and pathological processes including pain generation, modulation, and sensation. Its involvement in chronic orofacial pain (OFP) in general, and the reflection of its involvement in OFP in salivary endocannabinoid (eCBs) levels in particular, has not been examined. Objectives: to evaluate the association between salivary (eCBs) levels and chronic OFP. Methods: salivary levels of 2 eCBs, anandamide (AEA), 2-arachidonoylglycerol (2-AG), 2 endocannabinoid-like compounds N-arachidonoylethanolamine [anandamide (AEA)] and 2-arachidonoylglycerol (2-AG). Both ligands have a high affinity to cannabinoid-1 and 2 receptors , which are also activated by Δ9-tetrahydrocannabinol (Δ9-THC). This psychoactive component found in marijuana has pain reducing effects  AEA. Sample levels of AEA, 2-AG, AA, PEA, and OEA were measured against a standard curve and then expressed as fmol/mg proteins.The extraction, purification, and quantification of saliva eCBs was performed by stable isotope dilution liquid chromatography/tandem mass spectrometry (LC-MS/MS) as previously described by us ,40,41,42t-tests and one-way analysis of variance were performed, additional post-hoc Scheffe tests were performed when differences were significant. Spearman coordinator was used to examine the specific categories that made up the differences. The differences between eCBs types and specific background variables were examined for each diagnosis separately by using the non-parametric Mann Whitney and Kruskal–Wallis test.To examine the differences in eCB levels for nominal and categorical background variables, Of the 126 participants in the study, 83 had chronic OFP , 21 25.A. The re64 chronic OFP patients used pain medication including: Tricyclic antidepressants—Amitriptyline, Nortriptyline (27 patients), Pregabain (10 patients in the neuropathic group), Carbamazepine (10 in the neuropathic group), Topiramte (10 patients in the neurovascular group), Duloxetine (3 patients), Clonazepam (10 patients in the neuropathic group), Valporic Acid (1 patient in the neurovascular group), Tripans . Some of the patients used more than one medication (for details see: p < 0.001) , women had lower levels of 2-AG and AA than men in the neuropathic group —data not shown.Mean salivary levels (fmol/mg protein) of eCBs: AEA, 2-AG, OEA, PEA, and AA are summarized in < 0.001) . Specifip = 0.02), and 2-AG (p = 0.01) in the control group compared to the pain groups. The lower part of the table summarizes the differences in salivary eCBs in the three pain groups  compared to controls. p = 0.02, 0.04, respectively), 2-AG was lower in the neuropathic group (p = 0.05). No significant difference was found between the musculoskeletal group and controls.p = 0.028) between those with mild versus moderate and severe pain.1Rs within the CNS [1Rs and CB2Rs peripherally [1R expression was lower in mice with neuropathic diabetes compared to controls [2R levels are lower in chronic versus acute pain patients [2R. The effect was unrelated to the CNS level, as sensation and acute pain threshold were unchanged [In this study, we highlight, for the first time, the significant reduction in salivary eCB levels in chronic OFP patients. Consequently, we suggest salivary eCB levels may be utilized as biomarkers for OFP. The ECS is involved in a number of physiological and pathological processes. Its anti-nociceptive effects appear to be mediated by CB the CNS ,44 and vpherally ,46. Paincontrols . Similarpatients . In contnchanged .1R, and CB2R signaling, and by serving as a prostaglandin precursor, thereby modulating inflammation and pain [Data on cannabinoid treatment for headache and OFP are of poor quality and based on case series, case reports, anecdotal reports or retrospective analysis . We hypoand pain . OEA levand pain  suggestsand pain . OEA mayand pain ,55.1R and CB2R experienced neuropathic pain, while overexpression of CB2R prevented pain [The neuropathic pain patients in the current study had significant reductions in salivary 2-AG levels. Indeed, decreased plasma 2-AG levels have been measured in neuropathic pain patients with optic neuromyelitis  Donvito ted pain .Consistent with this notion, we found that those with higher pain intensity had lower eCB levels  confirm the accuracy of these results for specific pain diagnoses and at different time points; (ii) investigate the effects of successful pain treatment on eCB levels; (iii) identify high-risk groups in order to enable early diagnosis, screening and therapeutic follow-up; and (iv) determine if salivary eCB levels are indeed related to central eCB ‘tone’.In conclusion, the findings of the current study, that salivary eCBs levels are lower in chronic pain patients than in pain-free individuals, may help select the best therapeutic interventions for these patients. For instance, specific medications or formulations may alter the enzymes involved in the breakdown/synthesis of eCBs, and indirectly affect eCB ‘tone’. Moreover, salivary eCB levels can be used as a diagnostic tool and predictor of success before medical cannabis is used in this patient population.


The aim of this study was to compare the correlation between preoperative quadriceps femoris muscle thickness and postoperative neuromuscular activation and quadriceps femoris strength in patients with and without patellofemoral pain after arthroscopic partial meniscectomy.A series of 120 patients were prospectively analysed in a longitudinal cohort study of patients scheduled for arthroscopic partial meniscectomy. The patellofemoral pain group included patients who developed anterior knee pain after surgery while the control group included those who had not done so. Patients with preoperative patellofemoral pain, previous knee surgeries as well as those on whom additional surgical procedures had been performed were excluded. Of the 120 initially included in the study, 90 patients were analysed after the exclusions.p = 0.008). The group of patients who developed anterior knee pain in the postoperative period did not show this correlation (n.s.).There is a direct correlation between preoperative quadriceps femoris muscle thickness and the neuromuscular activity values and the strength of the muscle at 6 weeks after surgery. These results were seen exclusively in the group of patients who do not develop patellofemoral pain (0.543, In patients without patellofemoral pain after meniscectomy, the greater the preoperative thickness of the quadriceps femoris, the more postoperative neuromuscular activation and strength they had. This correlation did not occur in those patients who develop patellofemoral pain after meniscal surgery.II. Quadriceps activation failure (QAF) occurs due to alterations in neural signalling caused by a reduction in alpha motor neuron pool recruitment and/or firing rate . It commActivation failure is the inability to completely volitionally contract the muscle due to alterations in neural signalling. It is common following any type of knee surgery , 14. If If these neural abnormalities are not targeted with specific interventions used to disinhibit an inhibited muscle, quadriceps dysfunction may persist and become a factor limiting successful postoperative knee management , 19.Quadriceps muscle hypotrophy (QMH) that occurs following knee surgery is also thought to contribute to persistent muscle weakness , 39 due Muscle hypotrophy as well as the delayed onset of electromyographic activity of the quadriceps femoris muscle after arthroscopic partial meniscectomy predispose to the development of postoperative PFP. Furthermore, these two risk factors also predispose to worse postoperative functional results .Despite the important role that the quadriceps muscle plays in this pathology, whether having greater quadriceps muscle thickness before surgery has any impact in the neuromuscular activation of this muscle in the postoperative period has not yet been studied. No prospective study investigating the development of patellofemoral pain after a knee arthroscopy has tested the electromyographic activity of the vastus medialis and vastus lateralis muscles and its relationship with the preoperative muscular thickness.The aim of this study was to compare the correlation between preoperative quadriceps muscle thickness, its postoperative neuromuscular activation and strength in patients with and without patellofemoral pain after APM.The hypothesis was that there is direct correlation between the preoperative quadriceps muscle thickness and its neuromuscular activity after an APM in patients who do not develop patellofemoral pain.Approval for the study was granted by the Ethics Committee of Clinical Research of Parc de Salut Mar Hospital, Autonomous University of Barcelona (CEIC no. 2014/5534). Between 2015 and 2017, a prospective longitudinal cohort study was carried out on consecutive patients who were scheduled to undergo APM. The inclusion criteria were that the patient be aged 18 years or older and have an acute symptomatic medial meniscal tear requiring surgery. All patients underwent the procedure at a maximum of 6 months of evolution from the meniscal tear. No differences were found in the time of evolution of the meniscal tear between the groups. The exclusion criteria included having had PFP prior to surgery, previous surgeries on the involved knee  or if there had been an associated surgical procedure  during the index procedure.For the reasons previously stated, 30 patients out of the 120 initially included in the study were excluded. Nineteen of the 30 had had PFP before surgery. The remaining 11 patients of those 30 had undergone an associated surgical procedure like meniscal repair (7), microfractures due to the incidental presence of a chondral injury (3), and there was 1 partial meniscal injury that was left untreated . As the surgery was of short duration, a tourniquet was used at a pressure of 100 mmHg above systolic pressure with prior exsanguination of the limb. In all cases, the arthroscopy was performed through routine anterolateral and anteromedial portals. None of the patients had a femoral or a sciatic nerve block subsequent to the procedure. No drains were used in any case.The patients underwent the operation on a day-case basis. The same anti-inflammatory and anticoagulant medication was given to all the patients during the postoperative period. All patients passed through a physical therapy program either in our institution or in external rehabilitation facilities after discharge. In both cases, the same postoperative guidelines were respected. It was a standardized physical therapy protocol based on immediate postoperative weight-bearing with crutches as tolerated, without bracing, until there was a normal gait pattern. Range-of-motion was not limited and progressed as tolerated.The progressive program that the patients followed included strengthening, proprioception and coordination and cardiovascular exercises. The program included targeted strengthening exercises for the lower extremity muscles . It went from isometric exercises to open chain exercises over 6 weeks. For the first 3–4 weeks after surgery, knee flexion during weight-bearing exercises  was limited to 60º. Exercise intensity, of a maximum of one repetition, ranged between 65 and 80% and the volume was three sets of 12–20 repetitions. With a focus on neuromuscular control of the operated knee, proprioception and coordination exercises included moderate intensity tasks . The 10-min cardiovascular exercise session called for cycling at light-to-moderate intensity. All patients received the same standardized physical therapy protocol after the surgery.Patients were assigned to a group depending on how they responded to a question relative to the presence of PFP at the preoperative visit and at 6 weeks after surgery . The question was then answered in writing by the patient.To quantify VM and VL muscle thickness, magnetic resonance imaging (MRI) of the thigh was taken for all patients before surgery and at 6 weeks after surgery. Those MRIs were done on both the injured knee and the contralateral knee. A high correlation coefficient exists between the quadriceps cross-sectional area and the total muscle volume . The kneLikewise, the electrical contractility of the quadriceps femoris was analysed with surface electromyography (S-EMG) (MEGAWIN), extracting muscle activity and the maximum voluntary contraction values of the VL and the VM during the preoperative period and at 6 weeks after surgery. Four Ag/AgCl surface electrodes (30 mm diameter) were distributed in the direction of the muscle fibres of the VM and VL, in accordance with the method for electrode placement in lower limb muscles S-EMG recordings described by Rainoldi et al. . Two addPatients were first informed about with electrical stimulation. Then, a single current intensity of 1-ms rectangular pulses was progressively increased in 10-mA steps (starting from 0 mA) every 3 to 5 s. Maximal current intensity was determined as the current level at which the evoked torque did not further increase despite increasing current intensity, indicating full quadriceps recruitment. Subsequently, the patients executed a standardized warm-up protocol consisting of 6 submaximal voluntary contractions and 1 maximum voluntary contraction (MVC) with 90 degrees of knee flexion. Next, patients completed 3 MVC trials separated by approximately 30 s. Standardized verbal encouragement and visual feedback were consistently provided to the patients. MVC torque was measured as the peak torque adjusted to body mass attained before or after the superimposed twitch . The actAn isokinetic test (Biodex dynamometer) was also performed both before surgery and 6 weeks after surgery to assess the muscle performance values. The tests provided data on muscular strength through range of motion at 60 degrees per second. The patients did the extension, with passive return to the starting position. Three repetitions were performed, and the median was chosen for each patient. The electrophysiological and isokinetic tests were performed on both knees by the same physiotherapist who was blinded as to whether the patient had patellofemoral pain.t tests. This was performed separately for the PFP group and the control group. The correlation between continuous variables were evaluated with Spearman’s rank correlation coefficients. STATA version 15.10  was used for the statistical analysis. p values of 0.05 were considered statistically significant.Numerical variables are expressed descriptively as mean and standard deviations. Within the groups, changes (preoperative vs. postoperative) were evaluated by means of paired A sample size calculation was made beforehand. Accepting an alpha risk of 0.05, a beta risk of 0.20 and a relative risk greater or equal to 0.10, 88 subjects were needed. The proportion of patients who developed PFP after surgery was estimated to be 0.25, the same as the incidence in healthy people , 31, 34.ResultsOf the remaining 90 patients after exclusion, 6 were lost to follow-up. The losses included 4 patients from the control group and 2 patients from PFP group. These follow-up losses were found to be non-differential for the statistical analysis of the data, because they did not affect the demographics of the two groups. Of the remaining 84 patients, 20 (23.8%) were allocated to PFP group for developing postoperative anterior knee pain, and 64 patients (76.2%) were considered controls. The mean age of the sample was 44.9 years SD 11.0 years). There were 29 women (34.5%) and 55 men (65.5%). Both groups were comparable in terms of all the preoperative variables analysed (Table 1.0 yearsp < 0.01)  Tables , 3, 4. A) Tables .Table 1SThere was a moderate positive correlation between preoperative quadriceps femoris muscle thickness and muscle activity, MVC and strength values at 6 weeks after surgery exclusively for the group of patients who do not develop patellofemoral pain. The group of patients who developed patellofemoral pain in the postoperative period did not show this correlation Table , 3, 4.The most important finding of the current investigation is that while a positive correlation exists between preoperative quadriceps femoris thickness and postoperative neuromuscular activation in patients without patellofemoral pain, this does not occur in those patients who develop patellofemoral pain after meniscal surgery. The results suggest that the delayed onset of electromyographic activity of the vastus lateralis and especially the vastus medialis muscle, regardless of muscle thickness prior to surgery, could be considered as a risk factor for the development of patellofemoral pain around the sixth week after APM.It is likely that there are a wide range of factors involved in the aetiology of anterior knee pain , 32, 33.The results indicate that patients in whom PFP appears after arthroscopic surgery experience muscular atrophy of the VL and, to a greater extent, the VM during a period of 6 weeks. This decrease in quadriceps femoris muscle size is probably related to postoperative proximity inhibition and the consequent failure of muscle activation. Then again, it might also be related to the development of PFP. This article goes further, as it shows the association between quadriceps activation failure and postoperative patellofemoral pain, even in those patients with good muscle thickness and good electrical contractility of the quadriceps muscles prior to surgery. In this line, QAF and QMH are crucial factors to target to improve the recovery of knee function following knee arthroscopy.Another interesting finding of the current work is the incidence of PFP after an arthroscopic meniscectomy in patients who did not previously have this pain. The 23.8% incidence of postoperative PFP is similar to that of patients after ACL reconstruction at the 1- and 2-year follow-up  . HoweverRecently, research has focused on developing specific disinhibitory interventions to improve voluntary quadriceps activation. Neuromuscular electrical stimulation has been shown to improve quadriceps function and strength, as well as decrease its atrophy in the postoperative period of ACL surgery , 19. EccA threshold of 6 weeks was set for the measurements. It is the moment in which the incidence of patellofemoral pain increases after knee arthroscopy , 2. In gA progressive pre-habilitation program that is mainly focused on strengthening the quadriceps femoris of subjects who have undergone meniscal surgery leads to improved knee function in the postoperative period, in the same way as happens in patients who have undergone ACL reconstruction , 19, 24.There are some limitations in the present study. One is the severity of meniscal damage and consequently the amount of meniscus removed at surgery, as they might have an impact on the degree of postoperative electrical contractility of the quadriceps femoris. Then, the definition of PFP, which is based on the presence of pain in the anterior part of the knee in a self-referral manner and not on more objective and specific measure score or patellofemoral questionnaires like the patellar diagnostic test (Felson).  Lower exIn the light of the current results, early activation of the quadriceps femoris after APM is particularly important for the prevention of postoperative patellofemoral pain, regardless of the quadriceps muscle thickness prior to the intervention.This study provide insights on the influence of neuromuscular control on anterior knee pain and how the postoperative rehabilitation protocol after meniscectomy should be approach. Those results may in turn be useful in guiding rehabilitation efforts and guide daily clinical practice after knee arthroscopy.In patients without patellofemoral pain after meniscectomy, the thicker the preoperative quadriceps femoris, the more postoperative neuromuscular activation and strength they have. This correlation did not occur in those patients who develop patellofemoral pain after meniscal surgery.


In addition, an elevated SPI at the end of surgery was able to predict moderate-to-severe pain with a sensitivity of 0.71 : 0.65–0.77; I2 = 29.01%) and a specificity of 0.58 . The overall accuracy based on the summary receiver operating characteristic (sROC) curve was 0.72. In conclusion, this meta-analysis highlighted the feasibility of the surgical pleth index to predict postoperative moderate-to-severe pain immediately after surgery. Our results from a limited number of studies warrant further investigations for verification.Despite acceptance of the surgical pleth index (SPI) for monitoring the intraoperative balance between noxious stimulation and anti-nociception under general anesthesia, its efficacy for predicting postoperative moderate-to-severe pain remains unclear. We searched electronic databases  to identify articles focusing on associations of SPI at the end of surgery with immediate moderate-to-severe pain in the postanesthesia care unit from inception to 7 July 2022. A total of six observational studies involving 756 adults published between 2016 and 2020 were eligible for quantitative syntheses. Pooled results revealed higher values of SPI in patients with moderate-to-severe pain than those without (mean difference: 7.82, 95% CI: 3.69 to 11.95,  Nociception is defined as neural encoding of actual or impending tissue damage , while pain is the subjective experience pertinent to impending or actual harm . Despitenorm) and pulse photoplethysmographic amplitude (PPGAnorm) from pulse oximetry measurements, has been proposed as a measure of the balance between noxious stimulation and anti-nociception during surgery under general anesthesia [The surgical pleth index , which is derived from the normalized heart beat interval  .We searched electronic databases, including Google Scholar, MEDLINE, Cochrane Library, and EMBASE, to identify articles focusing on the associations of SPI at the end of surgery with immediate moderate-to-severe pain in the PACU from inception to 7 July 2022. These databases were independently searched by two reviewers using the following keywords:  and . There were no limitations on gender distribution and language. We also screened for additional records through examining the reference lists of the acquired articles. The search strategies are available in Articles were considered eligible if the following PICOS criteria were met: (1) population: adults undergoing operations under general anesthesia being sent to PACU for postoperative care regardless of the type of surgery; (2) intervention: available SPI values before arousal at the end of surgery; (3) comparator: none; (4) outcomes: information about postoperative pain severity measured with reliable methods ) in the PACU; and (5) studies: observational studies with data on true-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values. For those without relevant information, adequate data for relevant calculation , and positive predictive value (PPV)) were deemed necessary. Discrepancy in opinion between the two reviewers regarding study eligibility was resolved through discussion with a third reviewer.The quality of the enrolled studies was evaluated by two independent reviewers with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) that comprised four domains, namely, patient selection, index test, reference standard, and flow and timing. While all four domains were used for risk of bias assessment, the first three were examined in terms of concerns regarding applicability . DisagreThe following items were extracted by two independent reviewers from the studies: (1) first author’s name (publication year), (2) gender distribution, (3) total patient number, (4) values of SPI at the end of surgery, (5) incidence of moderate-to-severe pain, (6) patient age, (7) area under the curve (AUC), (8) cut-off values of SPI for prediction of moderate-to-severe pain, (9) sensitivity/specificity or PPV/NPV, and (10) country. The definition of moderate-to-severe pain was based on that of individual studies. Inconsistent data were resolved by consensus-based discussion.2 statistics was used to evaluate statistical heterogeneity across the included studies based on a random effects model. The overall accuracy was assessed with the AUC derived from the summary receiver operating characteristic (sROC) curve.The statistical analysis was previously reported in our studies ,28. The p < 0.05. The MIDAS command in Stata 15.2.4. was adopted for graphic presentations of Forest plots on pooled sensitivity and specificity, sROC curve, Deeks’ funnel plot, and Fagan’s nomogram plot.Posttest probability was evaluated with Fagan’s nomogram plot analysis according to pretest probability and LR (+)/LR (-). Fagan’s nomogram plot, a graphic tool, consists of a line that is drawn from pretest probability to pretest probability through LR (+) and LR (-) in the middle of the graph with the intersection point being set as the new estimated probability. It was used to estimate the improvement in disease detection using the diagnostic approach in question as reflected by an increase in posttest probability or vice-versa for the prediction of the absence of a disease. Potential publication bias was detected with Deeks’ funnel plot asymmetry test with statistical significance set at The study characteristics are presented in The methodological quality of the included studies evaluated with QUADAS-2 is shown in p = 0.002, I2 = 46%)  .2 = 29.01%) and 0.58 , respectively  and LR (-) were 2.00 and 0.5, respectively . In our Accurate predictions of moderate-to-severe pain in patients immediately after surgery enable the implementation of prophylactic pain management strategies for improving the quality of recovery and subsequent care. Our study aimed to explore the efficacy of SPI for predicting postoperative moderate-to-severe pain in adults. We found that the values of SPI before arousal at the end of surgery were higher among surgical patients with moderate-to-severe pain compared to those without in the PACU . The pooled sensitivity, specificity, and AUC were 0.71, 0.58, and 0.72 respectively, suggesting that SPI may be a useful predictor of subjective pain perception in adult patients undergoing general anesthesia.In a large-scale retrospective study involving 92,136 surgical patients focusing on critical incidents including moderate-to-severe pain  and immediate complications in the PACU, the incidence of moderate-to-severe pain was 26.9%, which accounted for almost one-third of all patients in that study . MoreoveSPI, which is calculated based on the pulse photoplethysmographic amplitude and heart rate interval derived from pulse oximetry measurements, has been clinically used for intraoperative surveillance of the balance between nociceptive stimuli and antinociceptive drug effects . In commPostoperative pain is a subjective entity encompassing the physiologic, cognitive, and emotional aspects of a patient’s experience that cannot be objectively evaluated. In addition, other patient-specific factors  may also influence postoperative pain intensity ,43,44,45Two previous studies failed to identify a significant association between SPI and the severity of postoperative pain among awake patients ,47. SPI,A previous study reported a potential impact of age on the ability of SPI to discriminate differences in pain intensity in children at the end of surgery . In thatOur results should be judiciously interpreted in the light of several limitations in the present study. First, genetic factors, type of surgery, patient characteristics , anxiety, and other psychological stress were found to be predictors of postoperative pain and analgesic consumption ,53; howeThe results of the current study demonstrate the feasibility of using the surgical pleth index for predicting moderate-to-severe pain in the immediate postoperative period in the postanesthetic care unit. Further studies are required to investigate whether the incorporation of this monitor could improve the quality of acute postoperative care.


After propensity score matching for age and sex, 136 patients from each group were included in the study. Primary outcomes were the visual analogue scale (VAS) at rest, activity status at postoperative 6, 24, 48 h. Secondary outcomes were functional scores by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, Harris Hip Score (HHS) and rescue medications used. The postoperative VAS at 6, 24, 48 h at rest and 6 h at activity were significantly lower in the PCA + PNB group . There was no significant difference for postoperative 3-month HHS (p = 0.218), except for 3-month WOMAC index (p = 0.001). There were no significant differences for VAS between the PNB methods except femoral nerve block (FNB) and fascia iliaca compartment block (FICB) at postoperative activity 48 h (p = 0.028). There was no significant difference in the total count and amount of rescue medication  and difference in the quadriceps weakness was not noted. Therefore, PNB is beneficial for patients who undergo THA as it provides sufficient postoperative analgesia, especially during immediate postoperative resting pain without quadriceps weakness.This study aimed to evaluate the effect of a peripheral nerve block (PNB) on immediate postoperative analgesia and the early functional outcomes for patients who underwent total hip arthroplasty (THA). From January 2016 to August 2021, 353 patients who underwent THA were divided into two groups: the patient-controlled analgesia (PCA) group ( Total hip arthroplasty (THA) is the primary, most common orthopedic surgery to alleviate hip pain due to degenerative diseases by replacing pathogenic hip joint to artificial joint, resulting in improved quality of life ,2. As soA peripheral nerve block (PNB) for patients who undergo total joint arthroplasty is a recommended intervention with ERAS protocols ,12. PNBsCompared to studies about TKAs, there are fewer studies about the effect of PNBs for THAs. There are more PNB methods used for THA compared to TKA, and they are technically more demanding; FNB, quadratus lumborum block (QLB), fascia iliaca compartment block (FICB), lateral femoral cutaneous nerve block (LFCNB), and pericapsular nerve group block (PENG) ,18,19,20This study was hypothesized that adding PNB to conventional IV PCA will significantly alleviate pain after THA and improve early functional outcomes. This study aimed to compare the results of PNB administered in addition to intravenous (IV) PCA and IV PCA alone for the effectiveness of postoperative pain management, the difference in functional outcomes, and the effectiveness of various PNBs after THA.This is a retrospective study with propensity score matching to analyze the data. We reviewed the electrical medical records at a single tertiary hospital from January 2016 to August 2021 for patients aged > 20 years who underwent THA after a diagnosis of osteonecrosis of the femoral head or osteoarthritis of the hip joint . We obtained informed consent from all the participants for accessing their data before surgery and received approval from the Institutional Review Board of Severance Hospital . We included patients in this study whose data such as demographics, type of anesthesia, and American Society of Anesthesiologists (ASA) class was able to be collected by the researchers. The exclusion criteria were patients with inflammatory hip arthritis, rheumatoid arthritis, periprosthetic joint infection, history of revision surgery, patients with special devices due to severe instability, anatomical deformity, bone defects, and adverse reactions to opioids or anesthesia agents, and uncontrolled glucose levels.With these criteria, 353 patients were included and divided into 2 groups, with 217 patients who controlled postoperative pain using only intravenous IV PCA (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). Propensity score matching was performed for age and sex among these groups, and only 136 patients from each group were included in the study . FNB, QLAll THA operations were performed by a single surgeon with the patient in a lateral position. All surgeries were performed using a posterolateral hip approach and the short rotators were repaired. Thirty minutes before the end of the surgery, IV fentanyl 1 μg/kg and palonosetron 0.075 mg were administered to the patient for postoperative analgesia and antiemetic effects, respectively. All patients were administered IV PCA for 48 h postoperatively, which comprised fentanyl 7 μg/kg and palonosetron 0.075 mg , delivered as a 2 mL/h background infusion and 0.5 mL doses on patient demand with a 15-min lockout time. In the ward, all patients were administered celecoxib 200 mg orally and acetaminophen 1 g intravenously every 12 h. All patients started postoperative exercise following the same rehabilitation protocol. Alongside this, bedside exercises  were performed 0–6 h after the operation. Standing and walker ambulation was permitted on postoperative day 1 following the same protocol. Additional pain control was administered as rescue medication  through intramuscular injections.The primary outcome was pain intensity scores measured on a visual analogue scale (VAS) . VAS at rest and activity (during 45° passive flexion of the hip) were monitored for the first 48 h after surgery at 6, 24, and 48 h.Secondary outcomes included functional outcomes measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Harris Hip Score (HHS) at postoperative month 3 ,22. The t-test  or Mann–Whitney test . Categorical variables were compared using the chi-square test. The Kruskal–Wallis test was used to evaluate non-normal distribution in the continuous variables of multiple groups. The Bonferroni correction method for post-hoc tests was conducted if necessary. p-value < 0.05 was considered statistically significant in all cases. An analysis of data and propensity score matching was performed using the Statistical Package for Social Science software version 26.0 .Descriptive statistics were performed, and normality distribution analysis was assessed by the Shapiro–Wilk test. Continuous variables were analyzed using the Student’s The baseline characteristics of patients were compared for age, sex, body mass index (BMI), and ASA class between the PCA and PCA + PNB groups after propensity score matching .p = 0.000, 0.001, and 0.000, respectively, p = 0.004, p > 0.05, The VAS for THA were significantly lower in the PCA + PNB group compared with those in the PCA group at postoperative 6, 24, and 48 h during rest (p = 0.009)  .We also analyzed the total count of rescue medication prescribed during the first 2 postoperative days and converted the total dose of rescue medication within this period into a total morphine equivalent dose (mg) using converting factors ,24,25. Ap = 0.028, We conducted a subgroup analysis to review the analgesic effect of the PNB procedures. From the five PNB methods, we excluded QLB as it had been performed on a small number of patients . We combThis single-center, large-sample retrospective study investigated the analgesic effect and early postoperative functional outcomes of PNB by measuring the improvement in symptoms after the addition of PNB to conventional IV PCA. The study also investigated the effect of different types of PNB on pain control. The results showed that immediate postoperative pain in the first 48 h of surgery was significantly resolved by PCB with PNB compared with IV PCA alone. The periods studied were 0–6 h, 6–24 h, and 24–48 h, and all three subgroups at rest showed significant pain control with the PNB compared to the use of IV PCA alone. The period 0–6 h at activity also showed significant pain control with PCA + PNB compared to IV PCA alone. However, there was no difference in the analgesic effect of adding PNB during activity at 24 and 48 h postoperatively. Alleviated resting and activity pain in the immediate postoperative period after THA surgery is the most important finding of this study. As patients experience less pain after surgery, they require fewer pain medications such as opioids, which can lower adverse effects such as gastrointestinal discomfort. Moreover, this results in decreased level of delirium, which can lead to lower accidental fall rates while admitted in the hospital and unnecessary medical expenses. The results showed that the addition of PNB can decrease the total amount of opioid consumption as rescue pain medication .Patients who undergo THA experience significant postoperative pain . ProvidiPNB provides site-specific analgesia and has fewer adverse effects than epidural or intravenous anesthesia. Various studies have reported that patients administered PNB experience less urinary retention, hypotension, and nausea or vomiting than patients administered epidural anesthesia while maintaining a similar analgesic effect . All patFew studies have compared the early follow-up functional outcomes after THA. As our institute routinely measures the WOMAC index and HHS pre-operatively (one day before surgery), on postoperative day 90, and 6 months, and 1, 2, and 3 years after patients undergo THA, we were able to examine each patient’s functional outcomes after THA using these two scoring systems. We found that there were no significant differences in HHS between PCA only and PCA + PNB groups. Contrary to expectations, the WOMAC index of the PCA group at postoperative month 3 were lower than that of the PCA + PNB group. Hebl et al. (2008) reported that patients with PNB could sit up and walk significantly earlier than those who used PCA alone . The reaThe Department of Anesthesiology of our institution performed five different methods of PNB in the present study as mentioned above. Rashiq et al. 2013) conducted a systematic review of studies about randomized control trials between 1990 and 2010 to study the effects of PNB on patients undergoing hip surgery. This review concluded that a combination of an obturator and lateral femoral cutaneous block had the best analgesic effect on immediate postoperative pain, and a fascia iliaca block resulted in the lowest delirium rate . Wang et conducteThe strength of our study is in its larger patient numbers and control by propensity score matching. We investigated the effect of analgesia based on subjective pain and the functional outcomes for patients who underwent THA. Using statistics, we investigated the superiority of pain relief from the various PNB methods available. Lastly, this study addressed the analgesic effect of the combination of PNB and IV PCA, which most previous studies have not dealt with.This study has several limitations. First, this was a single-center, retrospective comparative study. We analyzed the pain management and outcomes of a large number of patients and performed propensity score matching to complement the biases. Since this study was not a randomized controlled study, there may be a patient’s selection bias. Second, several patients did not complete the WOMAC index and HHS during the surveys. Third, the bias from the pain scale and survey cannot be overlooked, as it is a subjective index. Fourth, the differences in the diagnosis of hip pathology were not included as a parameter. Fifth, the different types of THA implants by manufacturers were not considered.PNB has remarkable benefits for immediate postoperative pain control after primary THA. The analgesic effect of PNB with IV PCA was better than conventional IV PCA alone. There was no significant difference in the functional outcomes  of patients who had IV PCA and IV PCA + PNB. The analgesic effect among different PNB methods showed no significant difference. Further investigations are needed concerning the ideal, detailed regimen of PNB and various adverse effects such as in-hospital falls.