Despite advances in surgical techniques and peri-operative care, pain is a significant symptom post-operatively. The purpose of this study was to examine the attitudes, social norms, and behaviors of a cohort of nurses of various ethnic and cultural backgrounds regarding pain and pain assessment and management. The design was a descriptive qualitative study guided by Theory of Planned Behavior and the Theory of Transcultural Nursing. The sample included six registered nurses (RNs) , along with patients of the same and different cultural and ethnic backgrounds in the post-operative unit within 48 h of surgery. The nurses’ results indicated that nurses assess pain severity and patient treatment preferences yet do not conduct a comprehensive pain assessment and have limited knowledge of non-pharmacologic and complementary pain therapies. Despite knowledge of the patient’s pain history, tolerance, and cultural background, the nurses believed that “all patients should be treated the same” and were concerned about the use of opioids beyond the first 24–48 h post-operatively due to the risk of addiction and professional ramifications related to opioid administration. The conclusions are that ongoing education is needed regarding comprehensive pain assessment and pharmacologic, non-pharmacologic, and complementary pain therapies during the post-operative period. Discussion is needed regarding the importance of diversity and equity as it relates to cultural competence within the context of pain assessment and management to provide patient-centered individualized care. Pain, which is one of the oldest and most complex health problems, is an unpleasant sensory and personal experience with physical, emotional, social, and cultural characteristics that adversely affect the patient’s functioning and quality of life ,2. DespiAs pain management is a fundamental right of the patient , patientSince pain is a subjective experience, if a person says that he or she has pain, it should be accepted as true . Yet, itIn qualitative research, a research question states the phenomenon of interest and the population of interest. In this study, the research question was posed not as a declarative statement but as an interrogative question, specifically “What are the attitudes, social norms, and behaviors of culturally diverse nurses related to pain and pain management who are caring for patients during the post-operative period?”.This study was guided by the Theory of Planned Behaviors , which iGiven that there were no instruments with published reliability and validity to measure the concepts of this study, it was decided that the study design would be a descriptive qualitative study. This design may be guided by a conceptual framework which informs the development of structured interview questions. In this study, the interview guide asked about attitudes, social norms, and behaviors related to pain and pain management. As a qualitative study, the Standards for Reporting Qualitative Research (SRQR) informed the research process and critical appraisal criteria .The principal investigator (PI), as an international doctoral student, was funded by the Republic of Turkey Ministry of National Education. The Republic of Turkey Ministry of National Education stipulated that the study was to involve surgical patients, with the recommendation to study some aspect of pain and pain management. Both the PI and second author had surgical nursing experience, which informed the development of the research question and the study proposal. Their clinical expertise on post-operative units also informed the development of the interview questions and interpretation of the data.The nursing manager of the post-operative unit introduced the PI to the nursing staff to discuss the study. A flyer with the contact name of the researcher was distributed and posted to the unit to promote study recruitment. The purposive sample consisted of a cohort of 6 registered nurses (RNs)  who cared for patients within 48 h of surgery in the post-operative observation unit of a large tertiary medical system. Although the inclusion of Asian nurses was sought, there were no Asian nurses employed in the post-operative unit. The nurses’ inclusion criteria were the following: registered nurses (RNs) of identified ethnic or cultural backgrounds who worked in a post-operative unit, spoke English, and worked 12-h day shifts. The exclusion criteria included RNs who did not provide direct post-operative care. The ethnic groups identified in this study aligned with the ethnic groups identified by the National Institutes of Health in the US. Ethnicity refers to groups of people depending on their ancestry, social and cultural identity, race, language, country of birth, or other special characteristics of the society in which they were born, while culture is a social phenomenon that is generally based on the morals, values, beliefs, and characteristics of a particular group [This study was conducted in accordance with the Declaration of Helsinki. Study approval was obtained from the Institutional Review Board (IRB) of Florida International University  and the IRB of Baptist Hospital .Informed consent was obtained from all subjects involved in the study. Upon signing the informed consent, the participants completed a Demographic and Professional Data Form. Digitally recorded interviews were conducted in a private office in the unit, lasting approximately 45 min. To ensure confidentiality, the participants were assigned a code number to all study materials. The study data were kept in the PI’s locked file cabinet and a password-protected computer.A structured interview guide was developed based on the conceptual framework of the study and was informed by the surgical experiences of the authors. The interview guide was reviewed and revised based on the feedback of six master’s-prepared nursing students enrolled in a research project course taught by the second author.The sample of six nurses completed the Demographic and Professional Data Form, which was analyzed using descriptive statistics, and six interviews were digitally recorded and sent electronically via secure measures to a transcription company for transcription. The transcripts, as well as the researcher logs and analytic memos, were analyzed and coded according to Carini’s principles , specifiThe nurses’ ages ranged between 20 and 39 years, with 5 out of 6 reporting being female and single. Three of the nurses were born in the US, while the others were from Haiti, Cuba, and Guyana. They were of varying religious backgrounds. All of the nurses had a bachelor’s degree, worked as an RN for between 1 to 7 years, and worked from 2 months to 5 years in the post-operative observation unit. All the nurses stated that they did not receive formal training in pain assessment and management in their BSN programs. However, post-degree, half completed continuing education courses on pain assessment and management and received ongoing training in culture competence. In reporting the findings, pseudonyms were given to the nurse participants rather than the use of their initials.“Post-operative pain is expected. I explain that they are not going to be completely absent from pain, but I will help reduce it.”All the nurses stated that they expect pain in the post-operative period and that the pain would gradually decrease. However, they emphasized the importance of assessing pain intensity and cited their responsibility to act on the patient’s behalf by giving pain medications, advocating for acceptable pain control, and educating patients about what to expect following surgery. Nurse Clara said “It’s very subjective. Some people have more tolerance for pain, while others are less tolerant. People experience pain differently, and you should not judge anyone.”The nurses emphasized that pain is a subjective feeling which indicates that something is physically or psychologically wrong and necessitates a prioritization of patients in pain. Each believed that if a patient says he or she has pain, he or she should not be judged, and individualized care should be given. The nurses knew that patients reacted differently to pain due to differences in pain thresholds and tolerance levels. The nurses recognized that some people express pain verbally or through non-verbal gestures, such as facial grimacing. Nurse Alexandra said that “It’s when patients are yelling, screaming, cursing, that kind of behavior needs to be immediately addressed.” The nurses said that patients who report frequent pain are trying to attract attention, but they do not judge them. The nurses believed that if a patient asks frequently for pain medication, they need to learn about other pain medications or ways of reducing their anxiety. Nurse Amanda said that “I try not to judge them, like if they’re in pain and they require more pain medication, but it is important to follow the orders and hospital rules.” Nurse Clara emphasized that ‘’I just try to educate them, but it’s not our job to say you’re asking for it too much, if they have it ordered.”The nurses emphasized that they are concerned if a patient screams, yells, curses, or is demanding and aggressive, as it is “rude” to the healthcare team and shows “inappropriate behavior”. Nurse Clara stated that “When patients pressure nurses to move quickly, we are at greater risk of making mistakes.”All of the nurses recognized that developing a caring relationship with a patient is important in providing post-operative care, but that time is limited when patients only remain in the observation unit for 48 h. During this time, the nurses emphasized that supportive interactions included “trying to calm the patient by giving them attention and even changing the environment by decreasing noise and increasing privacy.” In return, the nurses felt that they “gained the patient’s cooperation” and that the patients were “more likely to follow the nurse’s instruction or advice.” The nurses spoke of the “demands that were made by some patients who were not understanding of their workloads and work stress” and that some patients were “constantly on the call bell”, while others “saw how busy the nurses were with other patients who were in severe pain”. Nurse Clara was concerned that The nurses were concerned that “patients may exaggerate their pain because they have a substance abuse history and are drug seeking”. Another nurse realized that “if a patient has had an opioid addiction, they may need more pain medications because they have a higher level of tolerance”. The majority of the nurses took a “neutral” and “nonjudgmental” approach, realizing patients also have “different personalities” and nurses are “responsible for minimizing pain”.“I notice some patients are better without the family interaction, as they follow instructions better when family is not present.”All the nurses recognized that pain restricts patient functions and movements, including activities of daily living, and with limited mobility due to pain, patients are at “greater risk for post-op complications, such as pneumonia, DVT, muscle atrophy, and alterations in the overall nervous system. Such restrictions and problems can also delay the healing process and recovery.” On a psychological level, the nurses cited that “patients in pain may be agitated, anxious, withdrawn, and at times, even ‘crazy’.” Pain affects “patients’ ideals and moral function” and may lead to a “decreased mood, increased stress, depression, hopelessness, as well as less willingness to cooperate”. The nurses also recognized the various relationships between pain and interactions with family. Depending on the patient and family, their communication may differ. “Some families worry too much about the patient and this may increase the anxiety of the patient.” Nurse Alexandra stated that “I ask them to describe their pain and rate the pain severity so I get a better understanding of what they’re feeling.”All of the nurses agreed that the patients’ verbal pain reporting is an important factor in pain management, stating “When the patient reports the pain before it is too bad, it is easier to manage.” The nurses believed that “patients verbal communication may not always be consistent with the actual intensity of pain.” Nurse Bibi stated that The nurses generally felt that adequate pain management is difficult if their patient workload is beyond two patients. Additionally, if another patient’s condition is life-threatening, such as with bleeding, then the patient in pain must wait for medication. Furthermore, patients with drug addictions or drug allergies have individual needs beyond the usual treatment plan, which complicates care. Pain assessment is also difficult if there is a language barrier or the patient is unable to communicate or is disoriented, “so, you cannot use the pain scale to determine pain severity”.“If the patient never had pain medicines I am okay with giving them a strong medication, but those with a drug dependency, I am concerned.” Nurse Charlotte emphasized that “Even with a substance abuse history, patients need their pain controlled. Short-term use is not a concern, but long-term use is a worry.”Five of the six nurses were concerned about the side effects of opioids after surgery. They believed that adverse effects could be life-threatening, such as impaired breathing, impaired renal function, electrolyte imbalances, GI bleeding, falling, or coma. They were also concerned about minor side effects, such as drowsiness, constipation, dizziness, nausea, and vomiting. They emphasized the importance of “educating patients about side effects, particularly of opioids”. In general, the nurses agreed that opioids are needed in the first 2 days following surgery, but after 2 days, the emphasis should be on the use of non-steroidal anti-inflammatory medications and non-pharmacologic treatments. Some nurses try not to give patients with substance abuse histories opioids and make an effort to try all other alternatives for pain management. Nurse Bibi explained that “I could dig into their previous problems to know if they are pain related.”The nurses wished they “knew in more detail the medical history and diagnosis” of the patients. They also wished to “learn more about different cultures about how to manage pain, so that they could try to put themselves in the patient’s shoes”. One nurse felt that “at times they were only second guessing”. Nurse Alexandra wished “I’m more understanding of someone from my culture because I understand why they feel that way.” Nurse Brandon, in contrast, stated “I’m Haitian and just because I don’t feel the need to express my pain does not mean that another Haitian person reacts the same way. So, I would treat the pain as it is presented to me.” The nurses recognized that the expression and reaction to pain may be different based on a patient’s cultural background and that a patient’s age may make a difference. It was emphasized that nurses should “talk to their patients to understand their culture and their preference for pain treatment.”Each of the nurses stated that regardless of the culture they were from, they gave the “same treatment and the same approach to the patients” and “treated them without discrimination based on their culture”. Yet, several of the nurses were more comfortable with patients who shared their culture or ethnicity because they had “a greater understanding of a patient from their own culture”. However, one nurse also emphasized that “despite coming from the same culture as the patient, it does not mean that all patients from a particular culture express pain or behave in the same way or feel pain the same way.” Nurse Bibi stated that “I won’t let them go with pain for a long time, but I have to prioritize patients.”The nurses reported that they “act quickly when the patient has severe pain”, “communicate with the doctor”, and “give the patient the medicine as soon as possible”. However, the nurses “have to prioritize the care of other patients if there is a crisis situation”. Nurse Clara said, All the nurses preferred pharmacological pain management for the first post-op day, but by day 2, they preferred not to administer opioids but give “a lower level of medication”. All the nurses asked the patients about their pain management preferences. The nurses reported that when a patient is in moderate to severe pain, they “take vital signs”, “check the patient’s position”, “evaluate the patient visually”, “ask about the cause of the pain”, “evaluate pain intensity using the pain scale”, and “check to see what is ordered to relieve pain”, as they do not want the patient to “suffer”. The nurses reported that depending on the severity of the pain, commonly used drugs are Toradol, Tramadol, Dilaudid, Morphine, and NSAIDS.“Patients should participate 100%. They should be taught how to manage the pain when they go home and, of course; whenever we give the pain medication, we tell them exactly what we’ve given them and how long it may start working.”The nurses felt that patients should actively participate in their care. They emphasized that patients “should know how to recognize pain” as well as “what has worked for them in the past” and “tell nurses their preferences for pain management”. The nurses believed that patients need to be educated about “when they can expect pain relief after receiving pain medication”, as well as other “non-pharmacologic treatments, such as a warm shower, repositioning or lowering lights to reduce pain”. Nurse Brandon said that “Sometimes, I may believe that certain treatments and complementary therapies are not effective. However, if patients believe that the treatment helps them, they should be allowed.”The nurses preferred to use non-pharmacological methods, such as heat or ice and repositioning, with pharmacologic methods, as “non-pharmacologic methods have no side effects and risk of addiction”. The nurses mentioned the value of a calm environment with decreased noise and light. Although one nurse mentioned the use of distraction, there was no discussion on the use of music, prayer, meditation, or other complementary therapies. Nurse Clara shared that “All MDs and NPs need to be better educated about pain assessment and management and work closely with nurses to ensure holistic pain management.”The nurses expressed several challenges, including “lack of orders for pain medications”, “physicians not seeing patients themselves after surgery”, “not being able to reach a doctor in a short time particularly on the night shift”, “lack of coordination between nurse practitioners who cover surgical practices”, and “the workload of the nurse which limits response time to patients”. The nurses also expressed challenges when they felt the “patient is being undertreated”. Sometimes, “patients’ medications may be insufficient”, while “some providers may not accept the nurses’ assessment and expressed concerns as they advocate for the patient”. The nurses indicated the importance of “developing pain protocols so that they could administer appropriate medications based on the pain assessments”. Nurse Amanda’s recommendation is that All the nurses in this study agreed that pain is a subjective experience, and a patient’s report of pain should be believed, as purported by Özveren et al. (2018) . The nurThe nurses believed that establishing a personal relationship with the patient was also important and wished there was more time to get to know the patient. They realized that the way a patient reacts is also different depending on the family involvement. The nurses did express distress when patients reacted to pain by screaming or being demanding or aggressive. Yet, the nurses often felt that the patients were not understanding of their workload. The nurses wished for potentially lower nurse-to-patient ratios to decrease their own work burden and respond more quickly to patients. Patients with substance abuse histories were also of concern, as they realized that the patient may have a different level of pain tolerance and require a higher dose of medication. Yet, addiction was of serious concern, with worry about negative work outcomes if the patient was overmedicated. The nurses in the post-operative setting did wish they had a greater understanding of the disease process and patients’ pain histories to guide their assessments and treatment of pain. They understood that a patient’s level of pain was also related to the extensiveness of the surgery. However, the nurses reported that their assessments focused on visually assessing a patient, and they depended on a patient’s rating of pain on the assessment scale. The nurses did not speak about conducting a comprehensive pain assessment, which includes documentation of the location of pain, quality of pain, duration, relieving and exacerbating factors, associated factors, or the meaning of the pain as per the patient . They diThe nurses did ask the patients about their preference for pain medications. However, they expressed significant concern if a patient had a strong preference, given the possibility of addiction. The nurses realized that in the first post-operative day, most patients experience moderate-to-severe pain and need IV pain medication. However, on post-op day 2, the nurses preferred to administer weaker medications by mouth, such as NSAIDS, to prepare patients for discharge home. The nurses expressed a preference for relieving pain using non-pharmacologic methods, such as positioning, walking to relieve gas, and creating an environment with minimal stimulation. However, they had limited knowledge of other non-pharmacologic pain treatments and the use of complementary therapies, such as music or distraction. Although these complementary therapies may be used in their personal or family context, this knowledge did not transfer to informing complementary therapies they could offer to their surgical patients. Midilli et al. (2019)  stated tConsistent with the nurses’ concerns, Şenyüz and Kocaşlı (2017) discussed the side effects of opioids used for moderate and severe pain, specifically the effects on respiration and bowel function . The nurWith regard to social norms, such as culture, the nurses expressed greater comfort in caring for patients of their same cultural or ethnic backgrounds, as they were more “familiar” with their expectations and behaviors. These results suggest that culture does play a role in nurses’ experiences when caring for patients of the same and different cultural backgrounds, which will be addressed more fully in another manuscript. Narayan (2010)  believedThe nurses expressed concern regarding overprescribing opioids, which could “get us into trouble” if the patient experienced negative outcomes related to opioid use. In contrast, the nurses indicated that physicians and nurse practitioners needed more education on prescribing appropriate doses of pain medication. An additional challenge expressed was the medical coverage of the unit, as there was often difficulty reaching practitioners post-operatively. The nurses were upset themselves when the pain medications ordered did not sufficiently relieve pain, and the provider did not come to see the patient but questioned the nurses’ judgement. Similar to Costello (2015) , who empThe nurses spoke of the importance of individualized care, recognizing differences in patients’ pain experiences and levels of pain tolerance, the extent of the surgical procedure, and differences in pain perceptions and preferences based on a patient’s cultural background. Yet, juxtaposed to this perspective, each of the nurses mentioned that they were taught to “treat all patients the same”. This potentially reflects a cognitive dissonance between patient-centered individualized care verses diversity and equity. “Treating all patients the same” may lead to a “one size fits all approach”. Access to adequate pain medications is important for all ethnic and cultural groups, but in the process of “standardizing” care, there may be a risk of jeopardizing patient-centered, individualized care. In addition, given that the nurses expressed greater comfort in caring for a patient of the same cultural background, it is unclear how this may negatively impact care offered to patients of differing cultural backgrounds from the nurse. For example, if vocalization of pain is culturally accepted, a nurse from a culture that has a stoic approach to pain may interpret “screaming” as an inappropriate pain response. Therefore, further understanding of cultural differences related to pain and pain responses needs to be discussed in educational offerings related to pain assessment and management.In reviewing the information shared by this cohort of nurses in a post-operative observational unit, several important issues have been raised: (1) the need for nurses to conduct a comprehensive pain assessment, (2) identifying the personal attitudes and preferences of nurses related to pain and pain management in comparison to patients, (3) exploring the impact of patients’ and nurses’ cultural backgrounds on pain management, (4) offering appropriate pain management in accordance with the level of pain severity, (5) using pharmacologic treatments, including opioids, non-opioids, and adjuvant therapies, and reassessment of pain following the administration of pain medications and other treatments, (6) increasing nurses’ and patients’ knowledge regarding the use of non-pharmacologic and complementary pain therapies, and (7) lastly, in consultation with pain management experts and unit management, determining the availability of non-pharmacologic and complementary therapies available during the post-operative hospitalization period.This study was approved by the institutional review boards during the first 3 months of the COVID-19 pandemic, a time when all hospitals were closed to visitors and on-site research could not be conducted. Data collection was therefore delayed until a COVID Mitigation Plan could be submitted, indicating measures to limit transmission of the virus. The time frame for data collection was also shortened, as only emergency surgeries were being performed in the first few months of the pandemic. As a further limitation, the researcher was working within a specified time frame to complete her research as stipulated by the Republic of Turkey Ministry of National Education, which funded the study. The nurses were also working under the stress of the pandemic, and the recruitment of nurses was challenging as they had time constraints related to time availability for interviews. Although the sample for this study included a cohort of six nurses of varying cultural backgrounds , no Asian nurses were working on the unit at the time of data collection, which was an identified limitation. Furthermore, the study consisted of nurse–patient dyads, with 6 nurses and 12 patients, 1 of the latter representing the same cultural background as the nurse and 1 patient being of a different cultural background from the nurse. Although a sample size of 18 participants was satisfactory for a qualitative study, the sample size of nurses was limited. Given the usual small sample sizes of 10–30 participants in qualitative studies, the results are not generalizable. However, the results provide a contextualized understanding of the human experience through intensive study of a few cases. Rather than the term generalizability often associated with quantitative studies, qualitative research speaks of transferability, which is known as case-to-case translation [Based on the results of this study, it is suggested that nurses on the post-operative unit have a greater understanding of the medical history and prior pain history of patients. In addition, nurses should receive education regarding conducting a comprehensive pain assessment, including visualization of the pain site. In continuing education seminars, perhaps in “unit huddles”, a nursing staff could discuss the challenges to pain assessment and management and discuss “case studies” representing patients who had significant pain management issues.Further consideration should be given to the nurses’ concerns about the use of opioids and opioid addiction. Nurses should be instructed regarding the use of the World Health Organization pain model, which indicates the importance of using non-steroidal medications, as well as adjuvant medications for mild pain (0–3 intensity), then adding opioids to this regimen in the face of moderate-to-severe pain . Given tGiven the nurse-to-patient ratios and consideration of emergencies other than pain management, the nurses expressed distress about workloads and feeling pressured when patients were extremely demanding, which may lead to an increased risk of medication error. This suggests the need for consideration of the nurse-to-patient ratios during a 12-h shift, given the types of surgeries scheduled. Written pain protocols may also be important in treating patients during the post-operative period, particularly if the prescription providers are not immediately available to write pain orders. NP coverage of the unit may ensure the availability of providers to write pain orders.Based on the results of this study, there remains concern that differences in the cultural backgrounds of the nurse and patient may influence the quality of care offered, specifically pain management. “Treating all patients the same” may result in stereotyping, in which the attitudes, norms, and behaviors of a person are contextualized primarily by culture. Nurses should be educated about assessing a person’s degree of assimilation in American culture and their individual perspectives regarding pain and pain management. In this study, the nurses expressed the importance of being non-judgmental, non-discriminatory, and accepting of diversity, yet juxtaposed to these ideas were the comments from the nurses to “treat everyone alike”. This negates the importance of diversity of needs, attitudes, preferences, involvement in deciding care options, and providing individualized care to meet the unique needs of patients. The implications and recommendations are for an emphasis on the importance of discussions between nurses and their patients in understanding health concerns, preparing patients for the surgical and post-operative experience, and offering guidance in a range of treatment options for pain.What does this paper contribute to the wider global clinical community? (1) It identifies the concerns of culturally diverse nurses in providing pain management for post-operative patients; (2) it indicates nurses’ challenges and recommendations regarding pain assessment and management; and (3) it highlights the issue of culture and cultural competence as it relates to standardization of pain management of patients verses individualized, patient-centered care.


The present research project is aimed at elucidating the application value of evidence-based care (EBC) in patients with lung cancer (LC) chemotherapy.  Ninety-four advanced LC patients visited between March 2019 and February 2021 were retrospectively selected. Based on the type of care, 44 cases who used routine nursing were set as the control group (CG), and 50 patients who received EBC were included in the research group (RG). The pain degree, adverse mood, and individual fatigue of patients were assessed, using the Visual Analogue Scale (VAS), Self-Rating Anxiety/Depression Scale (SAS/SDS), and Cancer Fatigue Scale (CFS), respectively. Besides, patients were assessed for treatment compliance, self-efficacy, and life quality using the treatment compliance questionnaire, General Self-Efficacy Scale (GSES), and Quality of Life Questionnaire Core 30 (QLQ-C30), respectively.  The VAS, SAS, and SDS scores were lower in RG versus CG after nursing intervention. RG scored lower in the dimensions of physical, affective, and cognitive fatigue in terms of individual fatigue assessed by the CFS and higher in various domains of the QLQ-C30 score after nursing intervention. Besides, higher treatment compliance and self-efficacy were determined in RG as compared to CG.  In addition to improving the treatment compliance, self-efficacy, and life quality of patients with LC chemotherapy, EBC can effectively alleviate their pain, adverse psychological mood, and individual fatigue, which deserves to be promoted in clinical application. Lung cancer (LC) is a fatal cancer represented by non-small-cell lung cancer (NSCLC), which causes approximately 2 million deaths worldwide every year . The disRoutine nursing intervention for LC patients undergoing chemotherapy often neglects psychological support, comfort care, pain threshold management, etc., which is difficult to mobilize patients' confidence to overcome the disease, resulting in a treatment outcome far from satisfactory . EvidencP > 0.05). The subjects not only knew the research purpose but also signed and provided the informed consent form.This research was conducted after obtaining approval from the Affiliated Hospital of Jiangnan University Ethics Committee. Ninety-four advanced LC patients visited between March 2019 and February 2021 were retrospectively selected and grouped according to different nursing patterns, with 44 cases receiving conventional care included in the control group (CG) and 50 cases receiving EBC assigned to the research group (RG). CG included 24 males and 20 females, with an average age of 59.86 ± 8.37 years and a disease course of 4.66 ± 2.03 years, while RG was composed of 29 males and 21 females that averagely aged 60.18 ± 10.68 with a disease course of 4.84 ± 2.24 years. The two cohorts were comparable in gender, age, disease course, and other general data  , with a Adverse mood: the Self-Rating Anxiety/Depression Scale (SAS/SDS) , both wiIndividual fatigue: the Cancer Fatigue Scale (CFS) , which iTreatment compliance: patients' treatment compliance was evaluated by the questionnaire of treatment compliance. Complete compliance was indicated if the patient was highly cooperative with the guidance of nurses and completed the guidance on time; basic cooperation with the guidance of nurses was regarded as partial compliance; failure to cooperate fully with the nursing staff and avoidance of nursing guidance is considered noncomplianceSelf-efficacy: patients' self-efficacy was assessed by the General Self-Efficacy Scale (GSES) , a measuLife quality: the Quality of Life Questionnaire Core 30 (QLQ-C30) was used to evaluate patients' quality of life from five domains : role, pAmong the above measures, the degree of pain, adverse mood, and individual fatigue were primary endpoints, while the others were secondary endpoints. In addition, all the above indicators were tested before and 6 months after nursing.n (%)), and a chi-square test was employed for intergroup comparisons. Denoted by mean ± SD, the measurement data were compared by independent sample t-test between groups and by the paired t-test among different time periods. A significance level of P < 0.05 was used in all analyses.GraphPad Prism 6  was used for data analysis and image export. The counting data were represented as case/percentage (P > 0.05), while significant pain relief was observed in both cohorts after intervention (P < 0.01), with lower VAS scores in RG as compared to CG (P < 0.01).We compared and analyzed the pain levels of two groups of patients after nursing intervention by the VAS , in ordeP > 0.05) and decreased notably in both cohorts after that (P < 0.01). The postintervention SAS and SDS scores were statistically lower in RG versus CG (P < 0.01).SAS and SDS scores in both groups were recorded before and after nursing intervention . SimilarP > 0.05), while after intervention, the scores of physical, emotional, and cognitive fatigue in terms of individual fatigue assessed by the CFS were lower (P < 0.05) and the GSES score was higher in RG (P < 0.01), with statistical significance as compared to CG.We evaluated patients' individual fatigue level and self-efficacy after nursing intervention by using CFS and GSES, respectively . The twoP < 0.05).Patients' compliance with treatment was evaluated through the compliance questionnaire . RG usinP > 0.05), while the score of each domain of the QLQ-C30 in RG after intervention was significantly higher than that before intervention and CG (P < 0.01).The QLQ-C30 scores were measured before and after intervention to analyze the impact of the two models of care on patients' life quality . The datLC is one of the prime reasons for global cancer-related deaths, with most patients being not diagnosed at an early stage due to the presence of nonspecific clinical manifestations . The comLC patients will experience physiological pain caused by chemotherapy during the treatment process. In addition, chemotherapy will kill a large number of healthy cells while destroying cancer cells, which will lead to decreased immunity, organ dysfunction, nausea, vomiting, fatigue, hair loss, and other adverse events , 26. In Still, there are some limitations to be addressed in this study. First, the analysis of sleep quality and respiratory function of patients with LC chemotherapy should be supplemented to help further understand the potential advantages of EBC. Second, the sample size of the experimental subjects is small, and increasing the sample size will help to further improve the universality of research results. Finally, the evaluation indexes of pain degree, individual fatigue, treatment compliance, self-efficacy, and quality of life of LC patients undergoing chemotherapy are relatively single. The nursing strategy can be further optimized if we can supplement relevant analysis of influencing factors on the treatment compliance of patients with LC chemotherapy. Future studies will be gradually refined from the above angles. In addition, the contribution of this study to the subject area and its novelty is as follows: first, starting from the common negative states of LC patients undergoing chemotherapy, such as pain, adverse mood, and individual fatigue, it is confirmed that EBC has a significant inhibitory effect on the above aspects; that is, it can significantly reduce patients' pain, bad mood, and individual fatigue. Second, in terms of self-efficacy, treatment compliance, and quality of life, it is proved that EBC has a significant positive impact on the above aspects; namely, it can significantly enhance patients' self-efficacy and treatment compliance, contributing to improved life quality of such patients. The above provides a new theoretical basis for the nursing choice of patients with LC chemotherapy.All in all, EBC is effective in the treatment of patients with LC chemotherapy, which can significantly reduce their pain and discomfort, relieve adverse mood and individual fatigue, and improve their treatment compliance, self-efficacy, and quality of life.


Parkinson's disease (PD) is commonly known as a disorder that affects the smooth performance of body movements. In addition to the motor impairments, patients with PD often experience pain. Both motor impairments and pain can occur throughout the body, hence including the orofacial region. However, currently, there is a lack of knowledge on the orofacial manifestations. Since orofacial pain and dysfunction can, amongst others, reduce the quality of life of patients with PD, it is important to explore the prevalence of these symptoms in the PD population.To provide a broad overview of the relevant literature on orofacial pain and dysfunction in patients with PD. Furthermore, we aim to generate hypotheses for future research on this topic.Embase.com, Web of Science [Core collection], and Cochrane Library) was performed on 20 January 2022, in collaboration with a medical librarian. In total, 7180 articles were found, of which 50 were finally included in this scoping review.A literature search  and temporomandibular disorder pain (N = 2)), orofacial motor dysfunction (e.g. limited jaw movements (N = 10), reduced maximum muscle output (N = 3), chewing difficulties (N = 9), unspecified TMD (N = 3), sensory disturbances (N = 1)), and bruxism (N = 3) were observed more often in patients with PD than in healthy controls.In the included studies, pain (e.g. orofacial pain (Patients with PD experience more pain in the orofacial area and more dysfunction of the masticatory system than their healthy peers.This scoping review can increase health care providers' awareness of the problems that can be encountered in the orofacial area of PD patients, especially pain syndromes also occur in the orofacial region and not only in the extremities. Besides, dysfunction of the orofacial area is elaborated in this scoping review, which helps to understand that this limits PD patients' quality of life. Further, the outcomes of this scoping review can assist in encouraging collaboration between medicine and dentistry. Finally, this scoping review suggests new research areas, based on the gaps identified in the current literature on this topic. Ultimately, this will improve individualized strategies for reducing orofacial pain and/or dysfunction in PD patients. Furthermore, we aimed to see which patient‐related characteristics are associated with orofacial pain and/or dysfunction in PD patients. Finally, we aimed to generate hypotheses for future research on this topic.22.1www.prisma‐statement.org) , and Wiley/Cochrane Library from inception to 20 January 2022, in collaboration with a medical librarian. The following terms were used (including synonyms and closely related words) as index terms or free‐text words: ‘Parkinsonian Disorders’, ‘Oral health’, ‘Oral functioning’ and ‘Quality of Life’‐statement (2.2Studies were included if they met the following a priori formulated criteria: (i) inclusion of patients with a diagnosis of PD; (ii) information on oral health‐related factors ; (iii) written in English or Dutch language. In addition, we excluded studies based on the following criteria: (i) the full text could not be retrieved, or it was not available; (ii) information on oral health‐related factors other than orofacial pain or dysfunction  independently screened all potentially relevant titles and abstracts for eligibility. Upon completion of the screening of all titles and abstracts, two reviewers (DE and ST) independently screened the full‐text articles of the included abstracts. Disagreements or doubts were dissolved through a consensus procedure with the third reviewer (MV).2.4All included studies were analysed using descriptive statistics, mainly percentages and means, including the standard deviations. In addition, all results were divided into: (i) within‐group results, to analyse the results for all PD patients; (ii) between‐group results, when a control group was included and comparisons could therefore be made. As part of this procedure, the following assumptions and choices were made , 33.1embase.com, 2860 in PubMed, and 2263 in Web of Science. After removing duplicates, 7180 references remained. Following the study‐selection procedure, 50 studies performed in 18 different countries and published between 1970 and 2022 were included: 5 RCTs, 27 case‐control studies, 14 cross‐sectional studies, and 4 case reports. The flow chart of the search and selection procedure is presented in Figure In total, 10,315 articles were found: 497 in Cochrane Library, 4695 in 3.23.2.1In total, nine studies reported unspecified pain in the orofacial area  and performance  in patients with PD Table . The witIn conclusion, in studies in which no distinction was made between pain or dysfunction, unspecified TMD is more prevalent in patients with PD than in controls.3.3.5Only three studies examined non‐painful TMD , fewer orofacial pain and/or dysfunction complaints, such as the presence of BMD, limited jaw movements, slower jaw movements and masticatory performance, seem to be present Table .4This scoping review aimed to give a broad overview of the relevant literature on the prevalence of orofacial pain and/or dysfunction in patients with PD and, when available, the comparison with controls. Furthermore, we aimed to see which patient‐related characteristics are associated with orofacial pain and/or dysfunction in PD patients and to generate hypotheses for future research on this topic. The majority of the studies showed that orofacial pain and/or dysfunction in the orofacial area are more common in PD patients than in healthy persons. Moreover, some studies found a correlation between, on the one hand, disease severity and other disease‐related factors (e.g. medication usage) and, in contrast, orofacial pain and/or dysfunction.In this scoping review, orofacial pain and TMD pain were more common in PD patients than in healthy controls. Pain, in general, is a common problem in patients with PD. Various types of pain have been described in PD patients , and several classifications and diagnostic tools have been proposed . Hence, because PD is a life‐long condition and because of the progressive nature of PD, the severity of the disease was probably relatively mild. Because suggestions are made that the severity of PD could be associated with pain and dysfunction in the orofacial area, one could reason that the reported findings represent an underestimation. Second, although this scoping review did not include a quality assessment, the majority of the included studies were of low to mid quality and were hampered by various sorts of bias . Third, the methodology of the papers, their outcome variables and the amount of included articles per subject prevented us from performing a meta‐analysis. Therefore, this scoping review presented the data descriptively. Fourth, not every article described how PD patients received a PD diagnosis (i.e. which criteria were taken into consideration to set the PD diagnosis). To be able to compare research on PD patients, uniformity is recommended. Fifth, when PD was present unilaterally, none of the articles mentioned which side was affected. Because the affected side reflects the pathophysiology of the degeneration in the involved hemisphere, it is possible that orofacial pain and/or dysfunction are present on that affected side as well. The prime strength of this scoping review is that it was performed in collaboration with a medical librarian who performed a systematic and extensive search in multiple databases. Therefore, this review provides a comprehensive overview of the relevant literature on this topic and thus on the gaps in the literature to be filled by future research. Sixth, limited data are available on the influence of therapeutic options for PD patients on orofacial pain and dysfunction complaints. Therefore, in the current article, we chose to only focus on the presence of orofacial pain and dysfunction, and the possible influence of disease‐related factors.4.2Limited high‐quality studies are available on orofacial pain and dysfunction in PD patients. Notwithstanding, this literature review can serve to increase the awareness of health care providers of the problems that can be encountered in the orofacial area of PD patients. Further, it can assist to encourage collaboration between medicine and dentistry. Finally, based on the outcomes of this scoping review, new research can be designed, based on the gaps identified in the current literature on this topic.5In conclusion, orofacial pain and/or dysfunction is more prevalent in PD patients than in controls. Furthermore, in some studies, a correlation was found between, on the one hand, disease severity and other disease‐related factors (e.g. medication use) and, on the other hand, orofacial pain and/or dysfunction. Based on our findings, a number of hypotheses could be formulated: (i) orofacial pain and/or dysfunction is more prevalent in PD patients than in controls; (ii) disease duration and severity are associated with a higher prevalence of orofacial pain and worse orofacial function in patients with PD as compared to controls; (iii) medication, for example, dopaminergic therapy, reduces the prevalence of pain, raises pain thresholds (temporarily) and improves orofacial dysfunction in patients with PD. To test these hypotheses, we recommend designing a study that includes PD patients with a wide range of disease stages, from disease onset to advanced stages of the disease, to study whether disease duration and severity are associated with more orofacial pain and worse orofacial function. In addition, disease‐related factors (e.g. dose of dopaminergic medication) should be included in future studies to establish whether or not these factors can influence orofacial pain and/or dysfunction in PD patients. Furthermore, using validated and internationally approved diagnostic criteria (e.g. for TMD diagnosis the Diagnostic Criteria for Temporomandibular Disorders [DC/TMD]) is highly recommended to be able to, for example, compare the results of different studies. Finally, an interdisciplinary approach is recommended to overcome bias related to the field of interest (Lobbezoo & Aarab, The researchers did not receive any grant from a commercial, public or not‐for‐profit funding agency to perform this study.MV, MK and FL conceived of the present idea. RdV performed the search. MV, ST and DE screened the results and extracted the data from the papers. All authors contributed to the clinical perspective and final review of this manuscript.The authors declare no conflicts of interest.Table S1Click here for additional data file.


To examine outcomes and complications following microdiscectomy for recurrent lumbar disc herniation.Prospectively collected data for patients operated at the Department of Neurosurgery, St. Olavs University Hospital, Norway, were obtained from the Norwegian Registry for Spine Surgery from May 2007 through July 2016. All patients underwent lumbar microdiscectomy. The primary outcome was change in the Oswestry Disability Index (ODI) at one year. Secondary endpoints were change in quality of life measured with EuroQol 5 Dimensions (EQ-5D), back and leg pain measured with numerical rating scales (NRS), complications, and duration of surgery and hospital stays.276 patients were enrolled in the study. A total of 161 patients (58.3%) completed one-year follow-up. The mean improvement in ODI at one year was 27.1 points . The mean improvement in EQ-5D at one year of 0.47 points , representing a large effect size (Cohens D = 1.3). The mean improvement in back pain and leg pain NRS were 4.3 points  and 3.8 points , respectively. Nine patients (3.3%) experienced intraoperative complications, and 15 (5.5%) out of 160 patients reported complications within three months following hospital discharge.This study shows that patients operated for recurrent lumbar disc herniation in general report significant clinical improvement. •Sciatica due to lumbar disc herniation (LDH) is the most common indication for spine surgery.•There are currently limited and conflicting data on what patients can expect when undergoing repeated surgeries for recurrent LDH.•The aim of this observational study was to investigate patient reported outcomes and complications following microdiscectomy for recurrent LDH.•At one year we found a significant improvement in ODI-score one year after surgery. We also found significant improvements in EQ-5D-scores, leg pain NRS and back pain NRS.•The major strengths of this study are a large number of patients, high external validity, prospective data collection, and widely applied outcome measures. RecurreThe aim of this observational study was to investigate patient reported outcomes and complications following microdiscectomy for recurrent lumbar disc herniation.22.1Data were collected through the Norwegian Spine Registry (NORspine), a comprehensive nationwide registry for quality control and research . Follow-2.2American Society of Anesthesiologists (ASA) grade, image findings, and surgical approach and procedure. The surgeons provided data on the following possible complications and adverse events to the NORspine registry: intraoperative hemorrhage requiring blood transfusion, postoperative hematoma requiring repeated surgery, unintentional durotomy, nerve injury, cardiovascular complications, respiratory complications, anaphylactic reactions, and wrong level surgery. Patients reported the following complications if they occurred within three months after surgery: wound infection, urinary tract infection, pneumonia, pulmonary embolism, and deep venous thrombosis. A questionnaire was distributed to patients by regular mail at three months and one year after surgery, completed at home by the patients, and returned. The patients who did not respond received one reminder with a new copy of the questionnaire. The patients completed preoperative questionnaire data and postal follow-up questionnaires without any assistance from the surgeon or other staff from the treating hospital.On admission for surgery, the patients completed the self-administered baseline questionnaire, which included questions about demographics and lifestyle issues in addition to the outcome measures. During the hospital stay, using a standard registration form, the surgeon recorded data concerning diagnosis, previous lumbar spine surgery, comorbidity, Information about previous or future surgery not originally registered in NORspine were collected from electronical patient journals.The study was evaluated and approved by the regional committee for medical research in Central-Norway (2016/840), and all participants provided written informed consent.2.3The primary outcome measure was change in disease specific functional outcome between baseline and one-year follow-up was measured with the ODI which has been translated into Norwegian and tested for psychometric properties . ODI con2.4Changes in health-related quality of life were measured with the Euro-Qol-5D (EQ-5D) instrument . An indeIntensities of back and leg pain were assessed on 0 to 10 numerical rating scales (NRS), with response options ranging from 0 (no pain) to 10 (worst imaginable pain) . The min2.5Lumbar microdiscectomy is the favored surgical strategy for recurrent LDH at our center regardless of earlier surgery for recurrent LDH in the index level and was performed on all patients. The procedure involves preoperative fluoroscopy for detection of the target level, paramedian or median skin incision of about 3 cm, straight or curved opening of the paravertebral muscular fascia, and subperiosteal release of the paravertebral muscles from the spinous process and basal lamina above and occasionally below the target disc-level. Self-retaining retractors, typically Caspar retractors, are introduced and an operating microscope is used for magnification. Following removal of scar tissue, flavectomy, and required bony decompression , the dural sac and nerve-root are carefully mobilized medially and the herniated disc evacuated. Removal of the disc herniation might involve entering the disc space or just removing a free sequestrated disc fragment (sequestrectomy).2.6t-test for normally distributed data.Statistical analyses were performed with SPSS version 25.0 . Statistical significance level was defined as p ≤0.05 on the basis of a two-sided hypothesis test with no adjustments made for multiple comparisons. Central tendencies are presented as means when normally distributed and as medians when skewed. We used the Chi square test for categorical variables. Baseline and one-year scores are compared with one-samples 2.7Missing data for ODI, EQ-5D, NRS back and leg pain was handled with mixed linear models. This strategy is in line with studies showing that it is not necessary to handle missing data using multiple imputations before performing a mixed model analyses on longitudinal data .33.1In total, 276 patients were enrolled in the study. A total of 161 patients (58.3%) completed the one-year follow-up period. Baseline characteristics, surgical treatments, and comorbidities are summarized in 3.2Changes in ODI between baseline and one year after surgery are presented in 3.3Changes in EQ-5D, back pain NRS, and leg pain NRS at one year are presented in There was a significant difference between mean preoperative EQ-5D score and mean EQ-5D score at 1 year . An effect size of 1.3 was found for change in EQ-5D at one year, indicating a large clinical difference between the two time points.The mean difference between the mean baseline value and one-year value in back pain NRS was 4.3 points (95% CI 2.2–3.2 P <0.001). Among patients with one-year follow-up, 94.3% experienced a clinically significant improvement (≥2 points).The mean difference between the mean baseline value and one-year value in leg pain NRS was 3.8 points , and 95.6% of the patients experienced a clinically significant improvement (≥2 points).Mixed linear model analyses showed similar results for all patient-reported outcomes.Complications are presented in A total of 37 reoperations were performed within 90 days of the initial surgery, and 23 of these (62.2%) were due to residual LDH. One reoperation was due to hematoma.4This study shows that microdiscectomy for recurrent LDH was associated with significant improvement across a wide range of patient reported outcome measures. Still, approximately one out of three patients did not achieve the desired improvement following surgery. The results from our study can be used to better inform patients about the likelihood of a successful surgical outcome and risks associated with repeat microdiscectomy.In total, 65.2% experienced a clinically significant improvement defined as an improvement of at least 13 ODI points. Among the patients with complete one-year follow-up, 54 (33.5%) experienced a change in ODI score of less than 33%. In addition, 25 patients (15.5%) had a raw ODI score of 48 or more or more after surgery. These have been suggested as criteria with high accuracy for defining failure of surgery for lumbar disc herniation . SeriousAmong the patients with complete follow-up, 42% experienced no or minimal disability at one year . This is a lower proportion than previously reported in a study that excluded patients who had undergone previous spine surgery and found that 69.4% experienced no or minimal disability .The mean improvement in ODI score of 27.1 points is less than what has been reported in both the SPORT trial  and prevStudies utilizing the Japanese Orthopaedic Association score have reported a percentagewise improvement ranging between 52 and 65% . These sPrevious studies have explored whether factors such as older age, obesity, duration of pain, and smoking influence outcomes following lumbar microdiscectomy . In pati4.1Our study is strengthened by prospective data collection, high external validity, and widely applied and validated outcome measures  Although5This study shows that microdiscectomy for recurrent LDH was associated with significant improvement across a wide range of patient reported outcome measures. Still, approximately one out of three patients did not achieve the desired improvement following surgery. The safety profile of lumbar microdiscectomy for recurrent LDH seems to be acceptable.


To study the changes in the intestinal flora and its relationship with nutritional status for patients with cancer pain.  A prospective research method was adopted. One hundred twenty cancer patients with cancer pain were selected as the research objects, who were treated in our hospital from June 2019 to June 2020, and 120 cancer patients without cancer pain were selected as the control group, who were treated in the same period. The differences of the intestinal flora and nutritional status of patients with different severity between the observation group and the control group were compared to analyze the changes of intestinal flora in patients with cancer pain and its correlation with nutritional status. t = 17.141, p ≤ 0.001), albumin (ALB) , prealbumin (PAB) , and total protein (TP)  in the observation group were significantly lower than those in the control group. There were statistically significant differences in HB , ALB , PAB , and TP  among patients with cancer pain of different severity. Through these two comparisons, their nutritional indicators showed a significant downward trend with the increase in the severity for cancer pain patients; the levels of Lactobacillus , Bifidobacterium , Enterococcus , and Eubacterium  in the observation group were significantly lower than those in the control group. There were statistically significant differences in the levels of Lactobacillus , Bifidobacterium , Enterococcus , and Eubacterium  among patients with cancer pain of different severity. After pairwise comparison, their beneficial intestinal bacteria were significantly lower than those in the control group with the increase in pain in cancer pain patients. Nitric oxide (NO) , galectin-3 , occludin (OCLN) , galectin-1 , zonula occludens protein 1 (ZO-1) , and cingulin  in the observation group were significantly lower than those in the control group. There were statistically significant differences in NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin for patients with cancer pain of different severity. By comparison, the NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin of the patients showed a significant downward trend with the aggravation of cancer pain symptoms. Through correlation analysis, the nutritional indicators of patients were positively correlated with intestinal microorganisms and intestinal barrier function.  Hemoglobin (HB) ( There was a significant correlation between the changes in intestinal flora and nutritional status for patients with cancer pain, which could be used as an important basis for improving the treatment of cancer pain. According to the survey of the World Health Organization , the gloMeanwhile, the stress response caused by pain would also cause the secretion of catechol, adrenergic hormone, glucagon, and cortisol to decrease, further affecting the metabolism of intestinal glycogen, protein, and lipid. The intestinal flora of the body presented a corresponding disorder with the influence of metabolic disorder, thus affecting the nutritional status of patients . This st2, and an average length of education of 14.65 ± 2.51 years. There were 25 cases of gastric cancer, 41 cases of lung cancer, 34 cases of liver cancer, and 20 cases of colorectal cancer. According to the numerical scoring system (NRS), 1-3 points were mild pain, 4-6 points were moderate pain, and 7-10 points were severe pain; there were 35 cases with mild pain, 40 cases with moderate pain, and 45 cases with severe pain. In addition, 120 cancer patients without cancer pain treated in the same period were selected as the control group. There was no significant difference between the general data of the two groups (p > 0.05), as shown in A prospective research method was adopted for this study. One hundred twenty cancer pain patients treated in our hospital from June 2019 to June 2020 were selected as the research objects, including 57 male patients and 63 female patients aged 45-59 years, with an average age of 55.69 ± 2.47 years, an average body mass index of 24.55 ± 5.41 kg/mThe inclusion criteria were as follows: (1) all patients met the diagnostic criteria for cancer pain ; (2) allThe analysis of nutritional indicators was performed: 5 ml of fasting blood was collected after all patients were enrolled in the group. The levels of hemoglobin (HB), albumin (ALB), prealbumin (PAB), and total protein (TP) were detected with an automatic biochemical instrument.Then, intestinal microbiota was analyzed: all patients were tested for feces after enrollment. The NEB DNA assay was used to compare the number of Bifidobacteria, Enterococcus, Lactobacillus, and Eubacterium.At last, the detection of intestinal barrier function was carried out: the colon epithelial tissue of the patient was taken as the research object by colonoscopy, and the abrasive treatment solution of the above samples was lysed with RIRP lysate. At the same time, after centrifugation at 1000 r/min for 10 min, the upper liquid was taken, and the above liquid was subjected to nitric oxide (NO). Meanwhile, galectin-3, occludin (OCLN), galectin-1, zonula occludens protein 1 (ZO-1), and cingulin were analyzed.There was a comparison of nutritional indexes between the observation group and the control group. The levels of Hb, ALB, PAB, and TP in the observation group and the control group were compared.There was a comparison of nutritional indicators for patients with cancer pain of different severity. The levels of Hb, ALB, PAB, and TP in patients with mild, moderate, and severe cancer pain were compared.There was a comparison of intestinal microorganisms between the observation and control groups. The numbers of Bifidobacterium, Enterococcus, Lactobacillus, and Eubacterium in the observation group and the control group were compared.There was a comparison of intestinal microorganisms in patients with cancer pain of different severity. The numbers of Bifidobacterium, Enterococcus, Lactobacillus, and Eubacterium in patients with mild, moderate, and severe cancer pain were compared.There was a comparison of intestinal barrier function between the observation and control groups. The levels of NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin in the observation and control groups were compared.There was a comparison of intestinal barrier function in patients with cancer pain of different severity. The levels of NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin in patients with mild, moderate, and severe cancer pain were compared.There was a correlation analysis. Linear correlation was used to analyze the correlation between intestinal flora, intestinal barrier, and nutritional status.n (%). The difference was statistically significant when p < 0.05.The data in this paper were collected and analyzed by SPSS 20.0 software. All the research data were positive distribution, where the measurement data were expressed as t = 17.141, p ≤ 0.001), ALB , PAB , and TP  in the observation group were significantly lower than those in the control group, as shown in HB , ALB , PAB , and TP  among patients with cancer pain of different severity. Through pairwise comparison, the nutritional indicators showed a significant downward trend with the increase in cancer pain severity, as shown in There were statistically significant differences in HB , Bifidobacterium , Enterococcus , and Eubacterium  in the observation group were significantly lower than those in the control group, as shown in Lactobacillus , Bifidobacterium , Enterococcus , and Eubacterium  among patients with cancer pain of different severity. After pairwise comparison, their beneficial intestinal bacteria were significantly lower than those in the control group with an increase in pain in cancer patients, as shown in There were statistically significant differences in Lactobacillus , galectin-3 , OCLN , galectin-1 , ZO-1 , and cingulin  in the observation group were significantly lower than those in the control group, as shown in NO (There were statistically significant differences in NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin in patients with cancer pain of different severity. By comparison, NO, galectin-3, OCLN, galectin-1, ZO-1, and cingulin showed a significant downward trend with the aggravation of cancer pain symptoms, as shown in Through correlation analysis, the nutritional indicators of patients were positively correlated with intestinal microorganisms and intestinal barrier function, as shown in Malnutrition was one of the common clinical complications. Some research reports showed that , in treaIn this study, through the analysis of the nutritional indicators and intestinal microbial conditions of the patients between the observation group and the control group, the nutritional indicators and intestinal microbial conditions of the patients in the observation group were significantly lower than those in the control group. At the same time, the nutritional indicators and intestinal microbial conditions of the patients showed a significant downward trend with a significant increase in cancer pain. During the invasion of tumor cells into surrounding tissues, it was bound to cause a significant increase in the level of inflammatory response and oxidative stress response in the above regional tissues , 19. In There are also some shortcomings in this study. The patients in this study are all from the same hospital, which is not representative of the patient's overall situation and will lead to some bias in the results. This study only found that changes in the gut microbiota of cancer pain patients are related to nutritional status, but which type of flora plays an important role, how does it work, and whether it is metabolites or other pathways have not been studied in depth. In addition, this study only studies several microbiotas. With the development of the microbiome, sequencing into an effective method can detect the various flora changes in the patient's body; through sequencing, there will be more accurate detailed results.In conclusion, there was a significant correlation between the changes in the intestinal flora and nutritional status for patients with cancer pain, which could be used as an important basis for improving the treatment of cancer pain.


Before treatment, the Kellgren–Lawrence (K-L) grade; minimum joint space width (mJSW); pressure pain threshold (PPT) and temporal summation of pain (TSP) at the affected joint, tibia, and forearm; Central Sensitization Inventory-9; and painDETECT questionnaire (PDQ) were assessed. Cluster analysis was based on the pretreatment NRS and change in NRS with exercise therapy to identify the subgroups of pain reduction. The pretreatment characteristics of each cluster were compared. According to the results of the cluster analyses, patients in cluster 1 had severe pain that did not improve after exercise therapy, patients in cluster 2 had severe pain that improved, and those in cluster 3 had mild pain that improved. The patients in cluster 1 exhibited lower PPT at all measurement sites, higher TSP at the affected joint, and higher PDQ scores than those in other clusters. There was no difference in the K-L grade and mJSW among the clusters. The subgroup with severe pain and pain sensitization or neuropathic pain-like symptoms at pretreatment, even with mild joint deformity, may have difficulty in achieving improvement in pain after 12 weeks of exercise therapy. These findings could be useful for prognosis prediction and for planning exercise therapy and combining with other treatment.Pain sensitization and neuropathic pain-like symptoms are some of the common pain symptoms in patients with lower limbs, including hip and knee, osteoarthritis (HOA/KOA). Exercise therapy has been the first-line treatment; however, the effects differ for each patient. This prospective cohort study investigated the relationship between the effectiveness of exercise therapy and pretreatment characteristics  of patients with HOA/KOA. We assessed the pain intensity using a numerical rating scale (NRS) before and after 12 weeks of exercise therapy in patients with HOA/KOA ( Lower limbs, including hip and knee, osteoarthritis (HOA/KOA) is the most common form of arthritis and a major cause of chronic musculoskeletal pain and disability worldwide , 2. OsteOA pain was found to be provoked by both nociceptive mechanisms and pain sensitization in the pain pathways of the central nervous system . NocicepThe goal of OA management is to control and improve pain, physical function, and health-related quality of life . NonpharPrior studies in OA have shown that pain reduction was divided into several types (based on a slow or rapid reduction in pain) and that pretreatment physical and psychosocial health factors predict the response to exercise therapy . HoweverThe present study aimed to identify the subgroups of patients with HOA/KOA who showed similar types of pain reduction with exercise therapy and to explore the associations between the types of pain reduction and the pretreatment characteristics of pain sensitization and neuropathic pain-like symptoms. We hypothesized that pain sensitization and neuropathic pain-like symptoms would influence the effectiveness of exercise therapy.This study used a prospective cohort design. Patients with HOA/KOA, who were newly referred for physiotherapy by an orthopedic surgeon, were identified at the Maehara Orthopedic Rehabilitation Clinic in Obu, Japan, between December 1, 2019, and March 31, 2021. The inclusion criteria were as follows: a diagnosis of HOA/KOA confirmed by radiographic findings (K-L grade ≥ 1), clinical pain as the primary musculoskeletal complaint, 40 years of age or older, and chronic joint pain for at least 6 months. The exclusion criteria were rheumatoid arthritis, lumbar spinal diseases with neurological deficits and radicular pain, presence of other pain types , previous hip and knee replacement, any type of surgery within the past 6 months, cognitive impairment, and severe medical comorbidities . In case of bilateral symptomatic OA, the more symptomatic hip or knee was defined as the affected joint. Patients were asked to refrain from normal exercise on the day they participated in the study procedure.Demographic data, radiologic findings, pain intensity within the last 24 hours , 0 to 10) , PPT andThe patients were interviewed to assess demographic characteristics . Pain symptoms and pain-related disability were assessed using subscales of pain and function in activity of daily living in the Hip Disability and Osteoarthritis Outcome Score (HOOS) , 24 or tPosteroanterior radiographs of the hip and knee with weigh bearing were assessed. The K-L grade  and miniQST was assessed at the affected joint, the tibialis anterior , and the extensor carpi radialis longus  , 29. The2 probe, in the following order at 5-minute intervals: affected joint, tibia, and forearm. The pressing rate was 30 kPa/s; two assessments were performed at each site, and the mean PPT value was used. The PPT of the affected joint was defined as the lowest PPT of the four sites in the affected joints [PPT and TSP were measured by a physiotherapist using a handheld pressure algometer  with a 1 cmd joints , 16.TSP is a method for assessing central sensitization by repeated pain stimulus . PressurCSI-9 was used to assess the central sensitization-related symptoms . The CSIThe PDQ was used to identify factors related to neuropathic pain . The PDQThe participants received standard exercise therapy that was individualized and supervised by physiotherapists at the participating clinic. Physiotherapists who participated in the study had joined a workshop on the pathogenesis of pain in OA and the recommended nonpharmacological treatments based on clinical practice guidelines. The recommended treatment included exercise programs that were individualized and progressive, considering the preferences and ability of the patients . The exeR” as calculated by Z translation to evaluate the magnitude of the effect size (r = Z/√N) [R (version 3.3.0). The significance level was set at P < 0.05.Data were presented as mean ± standard deviation (SD). Patient subgroups were formed using hierarchical agglomerative cluster analysis. Hierarchical agglomerative cluster analysis (Ward's method) was performed using the pretreatment NRS and the amount of change in the NRS from pretreatment to after 12 weeks to identify the pain reduction subgroup according to the distribution of pretreatment pain intensity and amount of change. The number of clusters was determined using gap values . Followi = Z/√N) . As an an = 46; KOA, n = 64) who received a diagnosis of HOA/KOA, 9 patients  were excluded because they did not attend the follow-up visit owing to personal reasons (n = 6), total hip replacement (n = 1), or total knee replacement (n = 2). There were 101 patients in this study, and the participant flowchart is shown in P = 0.608), sex (P = 0.680), BMI (P = 0.257), pain intensity (P = 0.624), or pain duration (P = 0.204). There were no adverse events due to this exercise therapy. Of the 110 patients  who were assessed at 12 weeks after pretreatment, 28  were categorized into cluster 1, 19  into cluster 2, and 54  into cluster 3. There was no significant difference in the proportions of HOA and KOA (P=0.135). The pretreatment NRS in clusters 1  and 2  were higher than those in cluster 3 (3.1 ± 1.1). The pretreatment NRS in clusters 1 and 2 were not significantly different (P=0.280). The posttreatment NRS after exercise therapy in cluster 1 (6.8 ± 0.4) was higher than those in clusters 2  and 3 . There was no significant difference in the posttreatment NRS between clusters 2 and 3 (P=1.000).Cluster analysis using the pretreatment NRS and amount of change in the NRS between pretreatment and after 12 weeks yielded three clusters. The demographic data are shown in R = 0.559, P < 0.001, rate of pain reduction: 73.7%) and 3  after exercise therapy, while cluster 1 did not show any significant reduction . The amount of change in the NRS from pretreatment to after 12 weeks in cluster 1 (0.4 ± 1.0) was lower than the amounts in clusters 2  and 3 . In addition, the amount of change in the NRS in cluster 2 was higher than that in cluster 3 . According to the results of the cluster analyses, patients in cluster 1 had severe pain that did not improve after exercise therapy; patients in cluster 2 had severe pain that improved, and those in cluster 3 had mild pain that improved.A significant reduction in pain was observed in clusters 2 (P=0.629) in the percentage of patients with each K-L grade. There were no significant differences in the mJSW among clusters 1, 2, and 3 (P=0.477). Additional analysis showed that radiographic findings in each cluster were not significantly different between HOA and KOA.The results of radiographic assessments are shown in R = 0.433, P < 0.001) and 3 . The mean PPT values at the affected joint in clusters 2 and 3 were not significantly different (P = 1.000). The PPT at the tibia in cluster 1 (198.5 ± 91.0) was lower than the values in clusters 2  and 3 . The mean PPT values at the tibia in clusters 2 and 3 were not significantly different (P = 1.000). At the forearm, the mean PPT in cluster 1 (189.8 ± 85.3) was lower than the values in clusters 2  and 3 . The mean PPT at the forearm were not significantly different between clusters 2 and 3 (P = 1.000).The PPT values for each cluster are shown in R = 0.261, P < 0.05) and 3 . The mean TSP in cluster 2 was higher than the values in cluster 3 . At the tibia, the mean TSP between clusters 1 (22.6 ± 15.8) and 2 (11.1 ± 9.3) were not significantly different (P = 0.058). Moreover, the mean TSP in cluster 3 (4.6 ± 7.5) was lower than that in cluster 1  and was not significantly different from that in cluster 2 (P = 0.058). At the forearm, the mean TSP in clusters 1 (14.4 ± 14.8) and 2 (9.5 ± 9.9) were not significantly different (P = 1.000). The mean TSP in cluster 3 (5.7 ± 6.1) was lower than that in cluster 1  and was not significantly different from that in cluster 2 (P = 0.362).The TSP values for each cluster are shown in According to additional analysis, the mean PPT and TSP at the affected joint, tibia, and forearm were not significantly different between HOA and KOA in clusters 1 and 3. In cluster 2, mean PPT  and TSP  at all measurement sites were approximately the same level in both HOA and KOA. However, PPT and TSP could not be statistically analyzed due to the small sample size.P=0.882) and was significantly higher than that in cluster 3 . CSI-9 levels were not significantly different between clusters 2 and 3 (P=0.174). In cluster 1, 10 patients (36%) were classified as subclinical, 12 (43%) as mild, and 6 (21%) as moderate/severe. In cluster 2, 12 patients (63%) were classified as subclinical, 5 (26%) mild, and 2 (11%) moderate/severe. In cluster 3, 39 patients (72%) were classified as subclinical, 14 (26%) mild, and 1 (2%) moderate/severe. CSI-9 scores in each cluster were not significantly different between HOA and KOA in the additional analysis.The CSI-9 scores for each cluster are shown in R = 0.350, P < 0.01) and 3 . Moreover, the mean PDQ scores were not significantly different between clusters 2 and 3 (P=0.117). In cluster 1, 16 patients (57%) were classified as nociceptive, 9 (32%) as unclear, and 3 (32%) as neuropathic. In cluster 2, 18 patients (95%) were classified as nociceptive, 1 (5%) was classified as unclear, and none (0%) was classified as neuropathic. In cluster 3, 53 patients (98%) were classified as nociceptive, 1 (2%) as unclear, and none (0%) as neuropathic. PDQ scores in each cluster were not significantly different between HOA and KOA, according to additional analysis.The PDQ scores for each cluster are shown in In this study, pain reduction by exercise therapy in patients with HOA and KOA was divided into several types. Patients with severe pain had a longer pain duration and more severe pain symptoms, as well as more severe pain sensitization, central sensitization-related symptoms, and neuropathic pain-like symptoms than patients with mild pain. Moreover, the patients with severe pain that did not improve after exercise therapy had lower PPT values at all measurement sites, facilitated TSP at the affected joint, and higher PDQ scores. These findings indicate that pain sensitization and neuropathic pain-like symptoms are associated with the effectiveness of exercise therapy.Exercise therapy is recommended as a first-line treatment for painful OA , 19. HowOA is a chronic pain disorder involving nociceptive pain and structural joint damage. However, cross-sectional studies have shown that pain is not necessarily related to radiologic severity in patients with HOA/KOA , 5. The Several studies have reported that pain sensitization is associated with OA pain , 16. LowAdditionally, our study found differences in neuropathic pain-like symptoms at pretreatment, according to the type of pain reduction between each cluster. Recent studies have reported that neuropathic pain-like symptoms were quite prevalent in patients with HOA and KOA; respectively, 37% and 46% experienced at least one neuropathic phenotype –14. ThesOur study showed that while the CSI-9 in cluster 1 was higher than that in cluster 3, it did not differ from that in cluster 2. Central sensitization-related symptoms are a characteristic of chronic pain disorders, such as fibromyalgia, chronic widespread pain, and low back pain . Howevern = 32,599) has shown similar effects of exercise therapy on pain reduction in HOA and KOA patients [This study has several limitations. First, the participants in this study were HOA/KOA patients for whom physiotherapy was prescribed by orthopedic surgeons; this may have led to selection bias. Second, although our results showed no difference in the distribution in each subgroup, HOA and KOA may exhibit different characteristics. However, in this study, there were no significant differences in characteristics between HOA and KOA patients among the clusters. Furthermore, a recent cohort study (patients . Therefopatients . Thus, ipatients , it is pOur findings suggest that pain did not improve in HOA and KOA patients with severe pain symptoms, pain sensitization, and neuropathic pain-like symptoms after exercise therapy for 12 weeks despite mild joint deformity. However, exercise therapy may be effective in improving pain in patients who have severe pain without prominent pain sensitization and neuropathic pain-like symptoms. Thus, assessment of pain sensitization and neuropathic pain-like symptoms is required for adequate treatment selection and prognosis prediction. Future studies are needed to examine the effectiveness of pharmacotherapy and exercise interventions that primarily address pain sensitization and neuropathic factors in patients with OA who exhibit a low response to treatment.


Breast cancer (BC) is the highest frequent malignancy in women globally. Approximately 25–60% of BC patients with chronic neuropathic pain (CNP) result from advances in treating BC. Since the CNP mechanism is unclear, the various treatment methods for CNP are limited. We aimed to explore the brain alternations in BC patients with CNP and the relationship between depression and CNP utilizing resting-state functional magnetic resonance imaging (rs-fMRI).n = 20) and healthy controls (n = 20) underwent rs-fMRI. We calculated and compared the functional connectivity (FC) between the two groups using the thalamus and periaqueductal gray (PAG) as seed regions.To collect the data, the female BC survivors with CNP . Moreover, the Hospital Anxiety and Depression Scale-Depression (HADS-D) and pain duration were linked positively to the strength of FC from the thalamus to the SI. Furthermore, the thalamus-SI FC mediated the impact of pain duration on HADS-D.In BC patients with CNP, the ascending pain regulation mechanism is impaired and strongly associated with chronic pain and accompanying depression. This research increased our knowledge of the pathophysiology of CNP in patients with BC, which will aid in determining the optimal therapeutic strategy for those patients. Breast cancer (BC) is the highest prevalent malignancy affecting women globally . With inFunctional MRI (fMRI) is a commonly recognized method to examine brain function, especially in pain research. CNP involves morphological changes and functional adaptations of brain processing , 18. DamHerein, we utilized fMRI to evaluate neural changes in ascending and descending pain mechanisms in BC patients with CNP and to assess the link between CNP and depression in depth. We speculated that the FC between the thalamus, PAG, and other brain areas in BC patients with CNP was disrupted and that a defective FC may be associated with pain features and depression. If the hypotheses are confirmed, our study will enhance the understanding of the CNP in BC, which will greatly benefit the development of new treatments for BC.Our research complied with the recommendations of the Declaration of Helsinki, and the Local Ethical Institutional Review Board accepted the procedures. Before each procedure, all subjects signed informed consent. This research involved 20 right-handed patients with BC (20 women: mean age 52.25I ± 6.55 years) and 20 ideally suited healthy right-handed controls (20 women: mean age 49.95 ± 6.06 years).The inclusion criteria included (1) patients with BC survived 1-year or more post-therapy and experienced CNP for at minimum 3 months, (2) 18 years of age or older, and (3) a pain rating equal to or exceeding 3 out of 10. Exclusion criteria included (1) cognitive decline; (2) brain metastases; (3) past psychiatric disorders; (4) receiving central pain treatment throughout 1 month; (5) concurrent illnesses, like severe infection or systemic illness ; (6) past events of neural disorders or dementia, psychiatric illnesses, or failure to accomplish the test methods and MRI scans; and (7) an unwillingness to participate in the study.At admission, demographics  and clinical data  were acquired through self-reports and electronic health records.Peripheral painkillers were stopped 1 week before the fMRI scan, and no painkillers were given during the scanning to ensure the accuracy of the data. We recorded the duration of CNP for each patient as pain duration. The CNP of patients with BC was evaluated using the visual analog scale (VAS) score . Subjects indicated their current and historical pain levels by pointing to a spot on the line between the two faces. One experienced pain specialist measured the VAS (past) and VAS (during scanning) of patients to evaluate the pain intensity.The hospital anxiety and depression scale (HADS) is a 14-item self-reported survey with anxiety and depression subscale scores . HADS pet-tests, age and educational years variations between patients with BC and healthy controls were determined. A Chi-square test was utilized to examine gender disparity between the two groups.Using two-sample A Philips Ingenia 3T MR scanner  was employed to obtain 3T fMRI results. Subjects were asked to maintain their heads steady throughout scanning, and a sponge pad was utilized to limit unconscious head motion. Also, subjects were instructed to stay awake and close their eyes, and refrain from engaging in specific or intense thinking.3. Concurrently, high-resolution T1-weighted structural photos were acquired using a 3-dimensional magnetization prepared rapid acquisition gradient echo sequence (MPRAGE) with the next scanner metrics: TR = 7.44 ms, TE = 3.46 ms, flip angle = 8°, sagittal slices = 301, slice thickness = 1.2 mm, slice spacing = 0.6 mm, image matrix = 240 × 240, volume = 1, and voxel size = 1 × 1 × 1 mm3.BOLD signals were acquired utilizing a gradient-echo-planar imaging sequence (EPI) with the next metrics: TR (repetition time) = 2,000 ms, TE (echo time) = 30 ms, flip angle = 90°, slices = 36, slice thickness = 4 mm, slice spacing = 4 mm, matrix = 128 × 128, volumes = 200, volume interval = 2 s, and voxel size = 2 × 2 × 2 mm3; (4) the liner-drift, Friston-24 criteria, the white matter signal, and the CSF signal were retrieved as covariates and regressed to lessen non-neural signals; (5) a scrubbing action was also conducted for high motion time points; and (6) eventually, a band pass filter (0.01–0.08 Hz) was used to eliminate high-frequency noise influences and smoothed with an 8 mm full-width-half-maximum isotropic Gaussian kernel. Therefore, the collected finding was analyzed deeper.A brief description of preprocessing pipeline was as follows: (1) the initial 10 volumes of each functional scan matching every subject acclimation to the scanning setting and magnetization stabilization were neglected; (2) movement adjustment was conducted to lessen the impacts of head movement; and (3) functional photos were co-registered to structural photos and spatially normalized to the Montreal Neurological Institute template. Each voxel was resampled to 3 × 3 × 3 mmhttp://www.restfmri.net/forum/DPARSF) pipeline.Considering that the thalamus and PAG are important nodes in the ascending and descending pain mechanisms, they were selected as the starting points for the FC analysis of resting-state fMRI (rs-fMRI) data. To ensure homogeneity among all participants following standard fMRI analysis pipelines, the thalamus seed was derived from the Harvard Oxford subcortical structural atlas (90% threshold), a population-based probability atlas in MNI-152 standard space . The PAGp ≤ 0.001 was corrected for multiple comparisons using familywise error correction at the cluster level, matching to an adjusted p ≤ 0.05, using statistical parametric mapping . Subsequently, the mean value within the resultant cluster was extracted and linked to the clinical indicators in patients with BC.The mean time series of the thalamus and PAG were extracted, and voxel-wise FC was calculated between the thalamus and the remaining voxels within the brain. The same method was used to calculate the FC of PAG. The differences in the seed-based FC in patients with BC and HC were assessed using a general linear model within the gray matter masks. The grouping information was set as contrast while age, gender, and educational years were set as covariables to regress their linear effect on FC. http://processmacro.org, vs. 2.16.3) in statistical product service solutions , 95% confidence intervals (CI) for model parameters were determined. The objective of the mediation analysis was to examine if a significant variation existed between the total effect (path c) and the direct effect (path c′) that the mediator (M) accounts for. Two models were evaluated using the thalamus-SI FC as the mediator: (1) pain duration to be the independent variable and HADS-D ratings to be the dependent variable and (2) HADS-D ratings to be the independent variable and pain duration to be the dependent variable. A mediation was considered significant when bootstrapped upper as well as lower 95% CIs showed a number except zero.A bootstrapped mediation analysis was employed to evaluate the mediatory link among pain duration, HADS-D, and seed-based FC. Using 2000 bootstrap samples and the PROCESS macro , age , and educational years  demonstrated a non-significant variation between the two groups. Therefore, the quantified depression condition using HADS-D scales showed significant elevation in the BC group contrasted with the healthy group  vs. HADS-D: r = 0.49, p = 0.02; r = 0.60, p = 0.005; For patients with BC, Pearson correlation analysis demonstrated that pain duration and VAS (past) scores were positively linked to HADS-D scores  than healthy controls when the thalamus was set as the seed p < 0.05; 95% CI: , The thalamus-SI FC mediated the pain duration effect on HADS-D  40% of patients with BC with CNP had depression, and the HADS-D score was significantly linked to pain duration and VAS (past). (2) Contrasted to the control group, the BC with CNP group exhibited higher FC between the thalamus as well as SI, correlating with the HADS-D score and pain duration. (3) The thalamus-SI FC mediated the impact of pain duration on depression.Breast cancer is the highest frequent malignancy in women globally and accounts for 25% of female cancer cases . CNP andThe neuroimaging study of chronic pain has always focused on the study of pain modulation effects, including pain-associated brain areas and their pain regulation , 37. SinHerein, the raised FC of thalamus-SI showed probable function impairments in the ascending pain regulation mechanism in CNP-affected patients with BC. The overloaded input of spontaneous pain in the thalamocortical network might strengthen the association between the thalamus and SI , represeAs the main node in descending pain regulation, PAG is involved in many chronic pain disorders –53. UnfoWe further found that HADS-D and pain duration positively linked to FC between the thalamus and SI through linear regression analysis. This indicated that the malfunction of ascending pain regulation system was strongly linked to CNP and depression. We agreed with prior studies that the thalamus increased resting-state FC with the SI when the intensity and duration of pain increased . To explAccordingly, the present results demonstrated that patients with BC had impairment in ascending pain modulation pathways; pain duration can cause depression through the thalamus-SI connection, which would suggest that even if the relationship between pain and depression is reciprocal, causative effects on one another could be achieved through different neural systems. Indeed, the detailed neural mechanisms responsible for the causative effects need further investigation.The ascending pain regulation mechanisms exhibited deficits strongly linked to chronic pain and depression in patients with BC. This research boosted our knowledge of the pathophysiology of CNP in BC, helping to determine the optimal therapy for the patients. The clinical treatment of early pain in patients with BC should be emphasized to prevent the development of CNP. If the patient has developed CNP, paying attention to the depression and dealing with it in time while treating the pain is necessary.This study has some drawbacks. First, our investigation of the acute association between clinical symptoms and subcortical/cortical dysfunctions was hampered by the limited sample size of individuals with various disease severity and duration. Second, the thalamus has heterogeneous subregions, limiting the illustration of other detailed mechanisms. Third, this study is a complete analysis of the FC method in rs-fMRI, excluding other indicators ; we will do further research. Accordingly, we unselected the fMRI data of BC patients with CNP after medication and unexplored the functional differences of the brain after medication. In the future, we will use fs-fMRI to observe brain function changes after medication. Finally, we unexplored peripheral nerve conduction, which may require further clarification using fMRI of the spinal cord.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board of Affiliated Hospital of North China University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.