Objective: The objective of this study is to investigate the postoperative position of the patella and its relationship with anterior knee pain in patients operated with infrapatellar reamed tibia intramedullary nailing (IMN).Materials and methods: Patients who underwent tibia IMN between 2019 and 2022 and who had anterior knee pain in their postoperative follow-up at least two outpatient clinic controls with an interval of at least one month were examined. Patellar height indices  and sagittal angulation (patella-patellar tendon angles) were measured on the lateral direct radiographs of the patients in semi-flexion. As a control group, measurements were made on the contralateral intact extremity radiographs of the same patients.Results: There was no significant difference in patellar height indices between the fractured and intact sides in any of the patients . When the sagittal angulations were analyzed, a significant difference was found between the fractured and intact sides of the patients (p = 0.048), resulting in an approximate three-degree change.Conclusion: Patellar sagittal balance has been identified as one of the contributing factors to the development of anterior knee pain following reamed tibial IMN. Further biomechanical and comprehensive clinical studies are needed on this subject. Tibial intramedullary nailing (IMN) has been shown to achieve an 80% success rate in treating tibial shaft fractures . IMN mayKnee stability and extensor mechanism are significantly impacted by patellar height and the patellofemoral sagittal relationship -10. AlthThe present study aimed to investigate the relationship between the postoperative positioning of the patella concerning height and sagittal angulation as well as the incidence of anterior knee pain following tibial IMN.Medical records of 57 patients who underwent IMN of the tibia between May 2019 and January 2022 were examined, with the approval of the ethics committee . All participants aged 18 or over, who were able to move without pain before surgery, who underwent a minimum follow-up period of one year post-surgery, and who experienced ongoing anterior knee pain during at least two outpatient clinic appointments one month apart were eligible for inclusion in the study. Patients with tibial shaft fractures extending to the proximal or distal articular surface, those who received treatment with external fixator or plate osteosynthesis, those with polytrauma, those undergoing staged surgery, those with Gustillo-Anderson type 3 open fractures, those who reported anterior knee pain at postoperative follow-up, and those who declined to participate in the study were excluded. Type 3 fractures were not included in the study due to their distinctive follow-up and treatment mechanism in comparison to other types as well as the varied complication rates. A total of 57 patients received intramedullary nailing for fractures of the tibial shaft within the specified date range. Among them, considering the inclusion and exclusion criteria, 19 patients who persisted with associated anterior knee pain at least one month apart during their follow-up outpatient appointments were evaluated.Surgical techniqueAll patients received spinal anesthesia without a tourniquet while lying in the supine position. Following the recommended literature ,2,13, wePost-surgery, patients started with weight-bearing as tolerated and gradually increased it according to tolerance. If a lateral malleolus fracture was fixed simultaneously, load initiation would be delayed for a maximum of one month. Postoperative follow-up of all patients was performed without plaster/splint, and active-passive range of motion and quadriceps exercises were started on the first postoperative day with the help of physiotherapists.For patients with Gustillo-Anderson type 1 and 2 open fractures, reamed tibial intramedullary nails were used after antibiotherapy and washing in the emergency department . GustiloClinical and radiological examinationThe study collected demographic data, the mechanism of injury , the type of open fracture , the location of the fracture , and geometric fracture features  of the patients. Subsequently, the patients were contacted by telephone, using the contact details provided, to attend the outpatient clinic. Lateral direct X-rays were taken with the knee flexed at 30° to assess the sagittal angulation and patellar height. A comparison of preoperative and postoperative measurements for changes would have been desirable, but such measurements were not feasible, given the sudden nature of the injuries sustained by trauma patients. Hence, notwithstanding controversy in the literature, it was assumed that the patient's anatomy was equivalent on both sides, and comparisons were made with the whole extremity on the opposite side ,16. MeasThe Insall-Salvati (IS) index is calculated by dividing the length of the patellar tendon extending from the distal pole of the patella to the tuberositas tibia by the maximum length of the patella extending from its distal to proximal poles ,8 Figur, Panel AStatistical analysisThe statistical analysis was conducted using IBM® SPSS® program version 26.0 . To check for normal distribution conformity, both visual methods (histogram and probability plots) and analytical methods (Kolmogorov-Smirnov test) were utilized. Descriptive statistics were presented as mean and minimum-maximum values for normally distributed variables, median and minimum-maximum values for non-normally distributed variables, and percentage frequency values for categorical data. The paired samples t-test was utilized to compare fractured and intact side values of normally distributed data , whereas the Wilcoxon signed-rank test was employed to compare fracture and intact side values of non-normally distributed data (MIS and BP). Statistical significance was considered significant when the "P" value was less than 0.05.Of the 57 patients who underwent tibial IMN surgery at our clinic, 19 patients (33.3%) experienced anterior knee pain, with 15 (78.9%) being male and four (21.1%) females. The average follow-up period was 19.2 months (range: 12-28 months) from the date of measurement. No patients with anterior knee pain displayed any fracture in the proximal third region of their tibia or type 2 open fractures. None of the complex, irregular-shaped fractures were open fractures. No intraoperative observation of patellar tendon injury or rupture occurred in any patients. Table No statistically significant differences were observed in patellar height indices  between the fractured and intact sides of the patients . However, a statistically significant difference was found in P-PT angles between the fractured and intact sides of the patients when evaluated in terms of sagittal angulation (p = 0.048) Table .Anterior knee pain after tibial IMN is a common postoperative complication that significantly affects patients' quality of life ,3,5. IdeAnterior knee pain following IMN is a common complication, with a prevalence ranging from 30% to 50% according to existing literature ,3,5. ObrPatella alta poses a considerable risk for patellofemoral instability ,20, whicA statistically significant decrease in the postoperative P-PT angle was observed in our study (p = 0.048), resulting in an approximate three-degree change. The literature indicates that even slight declines in this angle value hold clinical significance due to the association between patellar tendon strain, imbalanced load anterior to the knee, and tendinopathy with P-PT angle values ,10,23,24Our study has various limitations. First, the control group used was the opposite knee of the patients. While literature reports anatomical similarities of both sides ,16, obtaAnterior knee pain is a common postoperative complication after IMN of the tibia, significantly impacting patients' quality of life and comfort. Our research found no conclusive evidence demonstrating the correlation between patellar height and anterior knee pain following reamed IMN of the tibia using the infrapatellar patellar tendon split technique. Nonetheless, we detected a notable relationship between alterations in sagittal angulation and anterior knee pain. Patellar sagittal balance has been identified as one of the contributing factors to the development of anterior knee pain following reamed tibial IMN. Further biomechanical and comprehensive clinical studies are necessary to fully investigate the correlation between the three-degree increase in sagittal patellar angulation and the occurrence of anterior knee pain.


Postoperative pain occurs immediately after surgery. The most common perioperative analgesic methods are nerve block, patient-controlled intravenous analgesia, and patient-controlled epidural analgesia. However, overuse of opioid analgesics can cause many adverse reactions including excessive sedation, respiratory inhibition, postoperative nausea, and vomiting. In recent years, many clinical trials have shown that perioperative acupuncture has unique advantages in patients. Perioperative acupuncture can relieve intraoperative pain, improve postoperative pain management, reduce postoperative nausea and vomiting, and shorten the length of hospital stay. This study aimed to confirm the analgesic effect of perioperative acupuncture by reviewing studies on the different methods of perioperative acupuncture and their analgesic effects. The cited literature was searched in English and Chinese from PubMed, China National Knowledge Infrastructure, and Wanfang data, using the following keywords: “perioperative pain,” “acupuncture,” “electroacupuncture,” and “perioperative analgesia.” Studies published from 2005 to 2023 were included. All retrieved papers were read in detail. Perioperative acupuncture has benefits in reducing postoperative pain and opioid need. Although analgesic drugs are still the primary means of postoperative pain control, acupuncture provides a safe analgesic supplement or alternative. This review aimed to assist practitioners in choosing appropriate perioperative acupuncture methods by summarizing the recent literature on the role of different acupuncture approaches for perioperative pain management. Local tissue or nerve damage caused by surgery can induce an excessive stress response in the body, activate pain receptors, cause the body to release harmful substances, and cause local or systemic neuro-endocrine changes, thereby causing tachycardia, hypertension, hyperglycemia, immune inhibition, platelet stagnation, and other symptoms. When pain associated with tissue injury and inflammation lasts longer than the expected postoperative healing period (≥2 months), persistent postoperative pain develops, which affects patients’ recovery time and can lead to mental, emotional, and behavioral changes. Currently, commonly used postoperative analgesic methods include intravenous application of opioids by medical personnel, patient-controlled intravenous analgesia (PCIA), patient-controlled epidural analgesia, and nerve blocks. However, opioids may cause adverse events, such as constipation, excessive sedation, respiratory inhibition, postoperative nausea and vomiting, and depression,,4 and previously opioid-free patients have a high rate of and severe consequences from opioid-related adverse events. Though opioid analgesia remains to be the major method for postoperative pain management, the result of its use has risks for patients even after discharge. Therefore, a multimodal approach for perioperative pain management has been promoted since it reduces dependence on drugs and improves outcomes. Current research suggests that acupuncture can reduce the pain response and increase pain tolerance as a result of various biologically active chemicals related to peripheral and spinal regions. Although its perioperative analgesia mechanism is not clear, the safety and promising advantages of acupuncture as a complementary and alternative medicine in perioperative analgesia has been confirmed in several clinical trials in recent years. Perioperative acupuncture analgesia is the use of acupuncture to reduce intraoperative pain stimulation and opioid need, improve postoperative pain management, reduce postoperative nausea and vomiting, and shorten hospitalization time. This is achieved by selecting acupoints along meridians, local acupoints, syndrome differentiation, and symptomatic acupoints according to different diseases and surgical sites. This review aimed to describe the postoperative analgesic effects of different perioperative acupuncture methods in recent years and to suggest a multimodal approach for perioperative pain management by using acupuncture for further research.Postoperative pain is a common type of clinical postoperative acute pain, including pain as a result of an operation, visceral trauma, and inflammatory stimulation around nerve endings following traumatic pain. An evaluation of 1490 surgical inpatients in the Netherlands showed that 41% of patients experienced moderate to severe pain on the day of surgery despite the presence of acute pain treatment regimens, and approximately 15% noted moderate to severe pain on the fourth day postoperatively.A search was conducted manually in English and Chinese using PubMed, China National Knowledge Infrastructure, and Wanfang data, using the following keywords: “perioperative pain,” “acupuncture,” “electroacupuncture,” and “perioperative analgesia.” Studies published from 2005 to 2023 were included. All retrieved papers were read in detail.Since this is a narrative review, ethical approval was not required.In all the typical cases analyzed, 22 studies confirmed that perioperative acupuncture had a significant analgesic effect, fifteen studies stated that it reduced or delayed the need for analgesic drugs, and 5 studies concluded that there was no significant pain reduction in the acupuncture group compared with the control group. Perioperative acupuncture has benefits in reducing postoperative pain and opioid need. Although analgesic drugs are still the primary means of postoperative pain control, acupuncture can provide a safe analgesic supplement or alternative. Due to the lack of multi-center and large-sample trials, the effect of perioperative acupuncture is still unclear.There are many methods of acupuncture commonly used for pain management, but few cases explored different acupuncture methods for the same type of operation. Therefore, we only classified acupuncture methods in this review to explore the analgesic effect of the different perioperative acupuncture methods.Traditional filiform needle acupuncture refers to the use of different acupuncture techniques to insert filiform needles into the patient’s skin causing mechanical stimulation of acupoints to produce anesthetic and analgesic effects. Unlike using sterile press needles, the filiform needles are not kept in place for a few days; they are removed after few minutes.P < .001). However, subgroup analysis indicated that, although the degree of postoperative pain in the acupuncture group was lower than that in the control group, the 2 groups were similar in reducing opioid analgesic use (P ≥ .412).Several clinical studies have shown that acupuncture can reduce the degree of pain during the postoperative acute pain period. A systematic review and meta-analysis involving 682 patients suggested that patients who received acupuncture or related techniques had less postoperative pain 1 day postoperatively, and their opioid analgesic consumption was less compared to the control group (P < .05), and there was no significant difference between them. However, the fourth day VAS score of the PCA group was significantly higher (P = .026), and the sixth day VAS score of the acupuncture group was significantly lower (P = .047) than that of other groups, and there was no significant difference in the decrease of VAS scores among the 3 groups over 6 postoperative days. This suggests that acupuncture might be as effective as traditional analgesia and PCA for adjuvant pain management postoperatively for lumbar degenerative disc disease. Interestingly, when the surgical results were assessed on the day of discharge, 26 patients (68.4%) in the acupuncture group reported either complete pain relief or significant improvement after operation, compared to 51.9% in the PCA group and 37.5% in the routine analgesia group (P = .024). These results demonstrated that patients who received acupuncture treatment reported either complete resolution or significant improvement of their back pain after the lumbar degenerative disc surgery in comparison to the routine analgesia and PCA groups. In another randomized controlled trial in 2023, a group of 58 patients undergoing lumbar spinal fusion were randomized to receive acupuncture before and after operation versus routine anesthesia alone. Though acupuncture was not shown to significantly improve pain scores (P > .05), the dosage of sufentanil and remedial analgesia within 48 hours after operation were significantly lower in the group receiving acupuncture (P < .01).In a retrospective study on postoperative analgesia after lumbar degenerative disc surgery, 96 patients divided into 3 groups received either acupuncture, patient-controlled analgesia (PCA), or routine analgesics for pain control. The results demonstrated that from the first postoperative day to the second, the visual analogue scale (VAS) pain scores of all 3 groups decreased significantly , and the requirement of analgesic drugs also reduced in comparison to the control group (P = .02). In another prospective randomized clinical trial, 251 children aged 2 to 10 were randomly assigned to either control or acupuncture groups. Children in the acupuncture group had less postoperative pain when they received acupuncture after anesthesia induction. The pain scores from 2 to 12 hours postoperatively in the acupuncture group were significantly lower than those in the control group (P = .001–.044), but no difference was found between 18 and 24 hours postoperatively or after discharge at home (P > .05). Though no difference was noted in the oxycodone requirements between the 2 groups in the hospital, a statistical reduction was showed on day 2 at home (P = .035).Two randomized trials showed that the use of traditional filiform needle acupuncture decreased pain in children with pain post-tonsillectomy. In a randomized, controlled, single-blinded study, a group of 60 children aged 3 to 12 were randomized to receive conventional postoperative analgesia and the same regime plus postoperative acupuncture, and the Wong-Baker Faces visual analogue pain scale was utilized to assess pain. In the group that received acupuncture, pain decreased significantly after the second and third treatments postoperatively  is different from electroacupuncture and traditional acupuncture. Instead of placing filiform needles, surface electrodes are used to stimulate acupoints with an electric current.P < .001). Also, the post mastectomy pain at 6 months after surgery was decreased in the combined acupoint group (P = .001).A multicenter randomized clinical trial involving 568 patients undergoing mastectomy investigated the effect of percutaneous acupoint stimulation before general anesthesia induction on post mastectomy pain. The results showed that the consumption of remifentanil during the operation and the amount of nausea and vomiting in the 24 hours after operation in the combined acupoint group were lower than those in the sham group (P < .001). There were no serious adverse events related to TEAS. Therefore, the clinical application of TEAS is safe and effective. Another randomized controlled trial showed that patients using TEAS before anesthesia induction had a significantly lower incidence of abdominal pain after colonoscopy (P = .007), and the incidence of abdominal distension was lower in the TEAS group (P = .032) than in the control group. Moreover, Szmit et al conducted a randomized, placebo-controlled study to assess analgesia requirement with TEAS in 71 patients after inguinal hernia repair. Patients who received TEAS showed significantly lower VAS pain scores (P < .001) and less total analgesia consumption in the postoperative period (P < .001) than others. Another prospective, randomized, placebo-controlled trial that included 60 patients undergoing gynaecological laparoscopic surgery demonstrated that patients who received TEAS for 30 minutes at the acupoints of Baihui (GV20), Yingtang (EX-HN-3), Zusanli (ST36), and Neiguan (PC6) before anesthesia had lower VAS scores on postoperative days 1 and 2 (P < .05).Furthermore, TEAS has a promising role in acute postoperative pain management in patients undergoing abdominal pain after surgical operation. A meta-analysis of 28 randomized controlled trials involving 2787 participants showed that TEAS could effectively relieve short-term pain after laparoscopic surgery, reduce the dosage of rescue analgesics after surgery, improve the quality of life of patients, and shorten the length of hospital stay . The consumption of sufentanil at 6, 24 and 48 hours during PCIA in the TEAS group was significantly decreased compared with the sham-TEAS group . Therefore, TEAS could offer a feasible and effective approach in the reduction of analgesic and pain management in patients undergoing thoracoscopic pulmonary resection. Moreover, Shun Huang et al conducted a randomized, double-blinded, placebo-controlled trial to explore the effect of TEAS used in different frequencies on video-assisted thoracic surgical patients. Eighty patients were randomly divided into 4 groups: control, 2/100, 2, and 100 Hz. The 3 experimental groups received TEAS at 2 Hz, alternating frequency between 2 and 100 Hz or 100 Hz frequencies for 30 minutes before induction, during the surgery and after surgery. The 2/100 group had the lowest opioid consumption  and lower VAS score than the control group (P = .047).TEAS is also a beneficial noninvasive pain management method for thoracic surgery. Jiheng Che et al conducted a randomized, double-blind, controlled experimental study on thoracoscopic pulmonary resection. The TEAS group received different degrees of TEAS before anesthesia induction, during the surgical procedure, and after the surgery. The sham-TEAS group also received sham stimulation before and after surgery induction as mentioned. The average VAS score at 6, 24 and 48 hours after surgery in the TEAS group was significantly lower than that in the sham-TEAS group  stimulates needles with an electrical current using an electroacupuncture machine after the needles are placed to “Deqi” to prevent or treat diseases. covering 11 cases of thoracotomy  showed that the pain score 24 hours postoperatively and the total dose of analgesics taken in the EA group were significantly lower than those of the 2 control groups. The pain score 24 hours postoperatively of EA group showed a standard mean difference of −0.98  and −0.94 (95% CI: −1.33 to −0.55) compared to the sham and conventional analgesia groups, respectively. The standard mean difference values of analgesic consumption of the EA and sham groups were −0.95 (95% CI: −1.42 to −0.47) and −1.96 (95% CI: −2.82 to −1.10), respectively, compared to conventional analgesia. In contrast, a subgroup study by Yu et al on cardiac surgery showed no significant difference in static and dynamic VAS scores between the electroacupuncture combined medicine group and the conventional analgesia group (P > .05). The injection dose of dexmedetomidine and morphine hydrochloride significantly decreased in the electroacupuncture combined medicine group (P < .05).A systematic review and meta-analysis by Park et alP > .05), but the VAS score of the experimental group was lower than that of the control group at 48 hours and 1 week postoperatively (P < .05). This demonstrates that EA may relieve postoperative pain in patients. Another prospective, randomized, parallel controlled study that enrolled 59 patients undergoing lumbar fusion surgery also demonstrated that patients treated with EA postoperatively had lower VAS scores (P < .05) and an increased degree of straight leg elevation (P < .05) compared to the patients treated with celecoxib.In addition, EA applied in the perioperative period can improve postoperative pain and the quality of life of patients undergoing lumbar surgery. Liu et al enrolled 62 patients who underwent modified transforaminal lumbar interbody fusion for lumbar spinal stenosis. The study compared those who were administered non-steroidal anti-inflammatory drugs (control group) and those who were administered analgesics combined with EA  postoperatively. The results indicated that there was no significant difference in VAS scores between the 2 groups before and 24 hours postoperatively (P < .001), 12 (P < .001), 24 (P = .547), and 72 hours (P < .001) after surgery. In a prospective randomized clinical trial, 124 patients receiving a procedure for prolapse and hemorrhoids were randomized into EA and control groups. Patients in the EA group received EA at Baliao point (BL31–BL34) and the surgery while patients in the control group receive the surgery only. The results showed that the EA group had lower VAS scores at 8, 24, 48, and 72 hours postoperatively  and lower frequencies of postoperative analgesic drug requirement per patient (P < .01) compared with the control group. Another RCT that enrolled 72 patients who had undergone hemorrhoidectomy and randomly received EA or sham acupuncture as a control also demonstrated that EA alleviated post-hemorrhoidectomy pain. The VAS scores of the EA group were significantly lower at 6 and 24 hours after operation and during defecation (P < .05) compared to the control group. Furthermore, the EA group also had lower Wong-Baker FACES Pain Rating scores at 5, 7, and 8 hours after treatment and during defecation (P < .05) compared with those of the control group.Some trials have also showed the promising role of EA for analgesia of hemorrhoids surgery. A meta-analysis of 5 RCTs comparing EA to a control group demonstrated lower postoperative pain scores in the EA group compared to the control group at 6 . Overall, this study concluded that perioperative acupuncture using imbedded needles relieved early postoperative pain, improved emotional state and comfort, and promoted patient recovery.A randomized controlled trial of performing sterile press needle acupuncture perioperatively with minimally invasive breast mass resections in 60 patients was conducted. The patients were divided randomly into the control group and imbedding needle group (ING). Approximately 30 minutes prior to surgery and after application of local skin disinfectant, the ING had their Neiguan (PC6), Waiguan (SJ5), and Hegu (LI4) acupoints needled. The needles were retained for 24 hours postoperatively, and the patients were instructed to press the acupuncture site intermittently to provide stimulation. The results demonstrated that the VAS scores in the ING were significantly reduced at 1, 2, 4, 6, and 8 hours postoperatively compared to that in the control group, and the number of patients receiving remedial treatment at 24 hours postoperatively was less in comparison to the control group (P < .05). In the acupuncture group, the dynamic incision pain scores at 8, 12, and 24 hours postoperatively decreased (P < .05), and the VAS pain scores of uterine contractions decreased at 8, 12, 24, and 48 hours postoperatively (P < .05). Additionally, the lactation score of the acupuncture group increased over 24 to 48 hours postoperatively (P < .05). In another randomized controlled trial, 180 female patients scheduled for elective cesarean delivery were randomized into an acupuncture group (n = 60),a placebo group (n = 60), and a nonrandomised standard care group (n = 60). Besides standard pain treatment, patients in the acupuncture and placebo groups received acupuncture with indwelling intradermal needles and placebo needles, respectively. The acupuncture group showed lower mean pain intensity on movement assessed with VRS-11 compared to the placebo group (P = .001) and the standard care group (P < .001). Moreover, 98% of patients in the acupuncture group were fully mobilized compared with 83% from the placebo group (P = .01) and 58% from the standard care group (P < .001) on the first day postoperatively.Two randomized trials exploring the use of sterile press needles for cesarean delivery demonstrated relief of pain. One randomized clinical study by Zhang et al investigated the effects of acupuncture in 135 puerpera after cesarean section. The women were randomly divided into 3 groups: the medicated, sham acupuncture, and acupuncture groups. The acupuncture group underwent PCIA with sterile press needle acupuncture and were found to have lesser dynamic incision pain and uterine contraction pain after cesarean section than that of the control and sham acupuncture groups combined (P = .04), and the AA group required 32% less piritramide during the first 36 hours postoperatively (P = .004). However, the pain intensity on the VAS-100 scores and the incidence of analgesia-related side effects in the 2 groups were similar. Another randomized controlled trial enrolled 60 patients after total knee arthroplasty who randomly received true acupuncture or sham acupuncture, and the AA needles were retained in situ for 3 days. The results showed that the acupuncture group had less requirement of fentanyl (P = .002) compared with the sham group.A randomized controlled study including 54 cases of total hip arthroplasty found that sterile press needles could be used to reduce the need for postoperative analgesia. Based on the results of random grouping, patients were allocated to receive auricular acupuncture with sterile press needles (auricular acupuncture [AA] group) or sham acupuncture (control group) in the evening before surgery, and needles were retained for 3 days postoperatively. The time taken for patients to request the analgesic piritramide postoperatively in the AA group was longer than the control group (P = .234–.888). Also, there was no statistical difference of pain scores at rest between the 2 groups within 48 hours of surgery (P = .134–.520); however, from the third day, the group that received AA showed significant pain relief compared to the sham group (P = .039–.047). Furthermore, no statistical difference was observed for total opioid consumption between 2 groups (P = .101). Additionally, this type of acupuncture did not demonstrate pain relief in a randomized controlled trial of thoracotomy. The acupuncture group even showed higher pain scores at day 30 after surgery (P = .9). No statistical differences were observed between the acupuncture group and the control group on pain assessments at 60 and 90 days after surgery .However, the advantage of sterile press needles acupuncture seems to be based on the type of surgery. A group of 40 patients undergoing open radical gastrectomy were enrolled into a randomized controlled pilot trial. Though both the sham group and acupuncture group (received AA 24 hours before surgery and remained for 6 days) had a declined tendency of postoperative movement-evoked pain scores, there was no statistical difference between the 2 groups at any observed point  and pain control postoperatively significantly improved (P = .0001), and the time before the patients requested the first postoperative analgesia was delayed (P = .0001).In a single-blind randomized controlled trial, 60 patients aged 3 to 12 years undergoing adenotonsillectomy were randomly treated with either general anesthesia or general anesthesia plus acupuncture. The acupuncture group received both filiform needle acupuncture and AA, which used sterile press needles. The filiform needles were inserted into the skin of the hands and feet <1 cm deep and were rotated counterclockwise to stimulate the acupoints every 5 minutes until the end of the operation, while the sterile press needles were placed on the ear lobe. Both needles were placed after general anesthesia and removed before the patient awakened. The Wong-Baker FACES pain scale was utilized to evaluate their postoperative pain in the post-anesthesia care ward. In the acupuncture group, both the intraoperative haemodynamic status (P = .029), there was no significant difference in the area under the resting pain curve between the 2 groups  (P = .439). Moreover, in all other secondary outcomes, including analgesic consumption, recovery time variables, quality of life, and incidence of opioid-related side effects, there was no significant difference between the 2 groups.However, the benefits of combined acupuncture are not the same. In a randomized controlled trial from 2016 to 2018, 72 patients who underwent laparotomy for gynaecological diseases were randomly allocated to the acupuncture group, which received both electroacupuncture and auricular acupuncture, or the control group, which received noninvasive sham acupuncture. The degree of postoperative pain was evaluated with the numerical rating scale 0 to 5 days postoperatively. The results indicated that although the acupuncture group had a smaller pain score at rest by 22 hours postoperatively than the control group  acupoint to complete the first reported surgery to relieve pain, acupuncture anesthesia began to flourish. However, with the emergence of new anesthetic drugs and the improvement of surgical technical requirements, acupuncture anesthesia cannot meet the needs for muscle relaxation, complete analgesia, and inhibition of reflexes. Therefore, Professor Xiong Lize of Xijing Hospital put forward the new concept of “acupuncture and drug balance anesthesia,” which refers to the application of combined acupuncture and anesthesia to make patients more stable in the perioperative period and improve their postoperative discomfort.In addition, there is limited literature to compare the interaction of different acupuncture techniques in postoperative pain management. This study reviewed the latest research progress on the role of different perioperative acupuncture methods in reducing postoperative pain and aimed to provide novel solutions for personalized multi-mode analgesia to improve the comfort of perioperative patients. Continued research of perioperative acupuncture with a more robust patient population may further clarify the role of acupuncture in postoperative analgesia, expand its clinical application, take maximum advantage of its effect, and provide novel solutions for postoperative analgesia.Thanks to the countless pioneers and scientists who passed down the traditional Chinese medicine for making it possible to combine traditional Chinese medicine with modern medicine.Conceptualization: Yuchang Dou, Ming Gao.Funding acquisition: Guoqing Zhao.Investigation: Ling Liu.Methodology: Ming Gao.Software: Longyun Li.Supervision: Peng Chen.Validation: Tao Li.Writing – original draft: Ling Liu.Writing – review & editing: Longyun Li.


Chronic pelvic pain syndrome (CPPS) is a frequent urological diagnosis that affects men’s quality of life. Extracorporeal shockwave therapy (ESWT) is a recent treatment option for patients with CPPS. We evaluated ESWT’s short and long – term efficacy in managing CPPS.This prospective self-controlled study included 75 patients diagnosed with CPPS at our tertiary pelvic pain clinic between January 2017-June 2019. Patients were referred for ESWT and received four sessions one week apart. The National Institute for Health – Chronic Prostatitis Symptom Index (NIH – CPSI) questionnaire was used to assess patients’ symptom severity before starting therapy and at 0, 12 and 26 weeks after completing ESWT. Demographics, clinical data and complications were also recorded.Patients’ mean age was 37.9 ± 8.6 years, and mean duration of symptoms was 5 ± 4.5 years. Compared to pre-treatment scores, all patients exhibited improvements across all NIH – CPSI domains directly after completing ESWT (week 0 post-treatment), with a mean difference improvement of 9.26 ± 5.7, 5.2 ± 3.4, 1.19 ± 2.18 and 2.88 ± 2.46 points in the total, pain, urinary symptoms, and quality-of-life scores respectively. At 12 weeks after completing ESWT, 80.9% of patients reported improvements, with mean difference improvement of 8.07 ± 7.56, 4.55 ± 4.6, 0.76 ± 2.48, 2.85 ± 2.78 in the total, pain, urinary symptoms, and quality-of-life scores respectively. Again, none of the patients developed any treatment-related complications. At 26 weeks after completing ESWT, 82.4% of patients reported improvements, with mean difference improvement of 8.29 ± 7.7%, 4.92 ± 4.69, 0.75 ± 2.96, 2.5 ± 3.0 in total, pain, urinary symptoms, and quality-of-life scores respectively. None of the patients developed treatment-related complications.ESWT is a safe and effective treatment modality for patients with CPPS, with short-term improvement in total, pain, urinary symptom, and quality-of-life scores; and long-term improvement in total, pain, and quality-of-life scores. Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) describes one of the common yet most challenging conditions to patients and urologists . The NatCP/CPPS is a multifactorial condition affecting men of a wide range of ages and demographics impeding their quality of life . Using vIn 1999, the International Prostatitis Collaborative Network (IPCN) developed and validated the National Institute of Health chronic prostatitis symptom index (NIH-CPSI) for the diagnosis of CP/CPPS . The indDue to the lack of consensus on the etiology of CP/CPPS, there is no established mono-therapeutic treatment recommendations . Many inGenerally, focused application of low-energy external shock wave therapy (ESWT) has been employed to manage orthopaedic pain syndromes . ESWT waThe literature reveals knowledge gaps. Most studies that assessed ESWT suffered from small sample sizes (range 20–30 patients) and/or short-term follow ups (range 2–3 months) . FurtherTherefore, the current prospective cohort study appraised the short and longer-term effectiveness of ESWT monotherapy among a large sample of CP/CPPS patients in a MENA country (Qatar). We assessed patients referred to our men's chronic pelvic pain clinic at the main tertiary care hospital in Qatar that manages CP/CPPS. Qatar is an Arabian Gulf cosmopolitan country where expatriates comprise about 75% of the population, many from various Middle-Eastern nations. The specific objectives of the study were to assess, among CP/CPPS patients, three domains: pain; urinary symptoms and quality of life; as well as patients’ total NIH-CPSI scores, and compare their pretreatment values with values at 0, 12 and 26 weeks post ESWT. In addition, we undertook a literature review of published articles on ESWT for CP/CPPS and selected examples that illustrated the wide variability in the actual practice/application protocols, as the well as evaluation of its effectiveness.Men attending the chronic pelvic pain clinic for the first time are thoroughly evaluated with history and physical examination. Different aspects of chronic pelvic pain are assessed and characterized including pain location, description and triggering factors. In addition, pain-related psychosocial symptoms, e.g. stress, anxiety, and depression are appraised. For lower urinary tract symptoms (LUTS) evaluation and bladder and prostate assessment, expressed prostatic secretions and midstream urine samples are cultured. When needed, flexible cystoscopy is performed to exclude anatomical and pathological abnormalities. Depending on the findings, patients are offered pharmacological and/or non-pharmacological therapies, including alpha blockers, antibiotics, antidepressants, anticholinergics, neuroleptics, phytotherapy, physical therapy, mental health therapy and ESWT.Of all the CP/CPPS patients attending our chronic pelvic pain clinic, 250 were eligible for and referred to ESWT treatment. We screened these 250 patients, out of which 120 patients were eligible to participate in the study. After explaining the purpose of the study to these patients, 75 agreed to participate and were recruited into this prospective self-controlled study to evaluate the effectiveness of ESWT among CP/CPPS patients. The study was conducted during the period January 2017-June 2019 at Department of Urology at our institution, the biggest tertiary care facility in Doha, Qatar. The Institutional Review Board at our institution provided ethical approval for the study (IRB# 16264/16).Inclusion criteria were adult men>18 years of age, complaining of pelvic discomfort, defined as groin, genitals, bladder, perineal and lower abdominal pain for ≥3 months, with no urological abnormalities, and with NIH-CPSI total score ≥15, negative urine culture, failure of pharmacological and/or non-pharmacological therapies, including alpha blockers, antibiotics, antidepressants, anticholinergics, neuroleptics, phytotherapy, physical therapy and mental health therapy to alleviate the symptoms , as well as patient ability to understand, communicate and comply with the study.Patients were excluded if diagnosed or recently suffered from chronic urethritis, urinary stones, bacterial or inflammatory CP/CPPS, seminal vesiculitis, urological cancers, urethral strictures, neurogenic bladder dysfunction, or intake of antimicrobial, anti-inflammatory medications, anti neuropathic agents or analgesics within four weeks prior to study enrolment. In addition, patients with documented history of prostatic intraepithelial neoplasia on biopsy, serum prostate-specific antigen levels >4 ng/ml, history of previous or recent spermatic cord denervation, prostate surgery or radiotherapy, acute urinary retention, and any history of drug/narcotic abuse were also excluded.Eligible patients were provided with ample information about the aim and purpose of the study, its steps, their role, and the period of involvement. Those who agreed to be included in the study received additional information about the treatment sessions, duration of each session, patients’ position, and any anticipated side effects. A final contraindication check list was conducted to ensure that all enrolled patients met the inclusion criteria. No additional pharmacotherapy was prescribed nor allowed during the treatment sessions and follow-up period.2 with a 3 Hz frequency.Patients received a total of four treatment sessions, one week apart using the Duolith SD1 Ultra Device . Each session lasted approximately 22 minutes, and the intervention was in the lithotomy position. The probe was firmly attached to the skin, after the application of ultrasound gel to ensure good wave transmission. In line with others ,12,14, tThe NIH-CPSI Questionnaire was used for evaluation of the outcomes  2]. It . It 2]. A formal literature review was performed using PubMed and MEDLINE databases. The search terms ‘ESWT’ or ‘external shock wave therapy’ or ‘CPPS’ or ‘chronic prostatitis’ or ‘chronic pelvic pain syndrome’ were used to identify articles that had these terms in the title, abstract or keywords. The inclusion criteria were English language studies reporting male adult patients presenting with CP/CPPS. Search results were reviewed for relevance, and we purposefully selected seven high-quality studies that illustrated the variability in practice and evaluation of effectiveness of ESWT.P value <0.05 was considered as statistically significant.Descriptive statistics summarized the demographic and clinical characteristics. Paired sample t-tests compared the pain, urinary symptoms, quality of life and total NIH-CPSI pretreatment scores with values at 0, 12 and 26 weeks after completion of ESWT. Results were presented as percentage frequency (%) of patients with changes in NIH-CPSI scores; and as mean ± standard deviation of NIH-CPSI scores. All statistical analyses were completed using statistical packages SPSS 19.0, and The sample’s mean age was 37.9 ± 8.6 years (range 18–60 years), with 3 years median duration of symptoms (range = 0.1–20 years). A total of 58 patients (77.3%) were married. Seven patients were diabetic (9.3%), 9 were hypertensive (12%), and 2 had cardiac conditions (2.7%). Before and during the ESWT treatment cycles, these 7 diabetic patients had not received Carbamazepine, Gabapentin or any other medications used to treat diabetic neuropathy. A total of 21 patients complained of erectile dysfunction (28%), 25 were smokers (33.3%), while 8 were ex-smokers (10.7%). No side effects were reported after the treatment sessions .Patients’ NIH-CPSI scores exhibited significant improvements at 12 weeks after completing the ESWT compared to pre-treatment values. In terms of patients’ response to treatment by NIH-CPSI domains, improvements were evident in the pain (76.1% of patients), urinary symptoms (53.7% of patients), and quality of life (73% of patients) domains; and 80.9% of patients exhibited overall improvements across all four NIH – CPSI domains . As for the mean NIH-CPSI scores, significant improvements were also observed in the pain (4.5 ± 4.6 points), quality-of-life (2.8 ± 2.7 points) domains, and total score (8 ± 7.5 points), while urinary symptoms (0.7 ± 2.4 points) improved but was not statistically significant.At 26 weeks after completing ESWT sessions, 57 patients were still present in the study. Compared to pre-treatment scores, the NIH-CPSI scores showed significant improvements at 26 weeks post-treatment. In terms of patients’ response to treatment by NIH-CPSI domains, improvements were evident in the pain (78.9% of patients), urinary symptoms (61.4% of patients), and quality of life (75.4% of patients) domains; and 82.4% patients exhibited overall improvements across all four NIH – CPSI domains . As for the mean NIH-CPSI scores, significant improvements were also observed in the pain (4.9 ± 4.6 points), quality-of-life (2.5 ± 3 points), domains, and total score (8.2 ± 7.7 points), while urinary symptoms (0.7 ± 2.9 points) improved but was not statistically significant.ESWT is an emerging and promising CP/CPPS treatment modality . Most stIn connection with maximum improvement, in the current study, maximum improvement in overall NIH-CPSI score was directly after the last ESWT session (week 0 post-treatment), where 97.3% of patients improved , and improvement was significant across the three NIH-CPSI domains of pain, urinary symptoms and quality of life. Such improvement of symptoms immediately after treatment completion is consistent with previous reports ,16, althP < 0.05). However, this durable improvement was statistically significant for the pain and quality of life domains, but not for the urinary symptoms.As for the durability of ESWT’s overall beneficial effects, others found that its effect was not sustained on the longer term, as there were no significant differences between the overall NIH-CPSI pre-treatment score and the final score 24 weeks after treatment completion . We obseCertainly, compared to pre-treatment levels, urinary symptoms showed intial statistically significant improvement at week 0 after treatment completion that were not sustained on the longer term (at 12 and 26 weeks). Our observed short-term ESWT effect on urinary symptoms concurs with others, where urinary symptom scores, urine flowmetry and postvoiding residual exhibited temporary early improvement after ESWT that were not statistically maintained on longer follow up ,12,13. WIn terms of mode of action, several theories have been proposed as to ESWT’s theurapetic effects on tissues . For insperse exerts unique additional benefical effects on top of those of the triple therapy.Some studies compared the effects of triple therapy alone  vs combined with 12-week ESWT sessions among CP/CPPS patients . This stAs for complications, throughout the current study, we observed no complications, and ESWT was well tolerated and accepted by patients. The 18 patients that dropped out of the present study were not because of complications or lack of tolerance to ESWT. Rather, these patients did not adhere to follow up visits as they became interested in starting physiotherapy or trying other treatment modalities. Our zero complication rate and good tolerance support previous reports confirmig ESWT’s safety and good tolerability as CP/CPPS management strategy ,17.A point to note is that our review suggested  a wide vThis study had limitations. The presence of a separate control group could have generated more concluisve evidence. In addition, evaluation of urinary symptoms was via self-reported NIH-CPSI score; objective urodynamic tests would have been useful to complement such subjective reporting. Increasing the follow up period would have strenghtened the reported effectivness findings of ESWT as a long term solution in pelvic pain management. Notwithstanding, the current study is one of the largest single arm studies evaluating ESWT’s effect on CP/CPPS symptoms for one of the longest follow up periods reported. The study sample is representative of the whole of Qatar, and not a single centre, as our facilitiy is the only tertiary care centre for managment of such patients in Qatar. Future research would benefit to assess the most effective ESWT therapy protocol, comparing e.g. different device settings, placement of the ESWT focus in relation to the points of maximal tenderness, as well as the frequency and spacing of treatment sessions.For CP/CPPS patients, ESWT is safe, accepted and well tolerated, with early relief of symptoms, starting directly after completion of treatment and effectively maintained through the long term for up to 26 weeks, particularly for the pain and quality of life domains. Urinary symptoms are intially improved but not statistically sustained on the longer term. Further evaluation of the treatment protocol/s that are most effective would be beneficial.


Due to the continued growth of surgical procedures in older adults and the significant impact of chronic postsurgical pain (CPSP), it is crucial to improve our understanding of the occurrence of CPSP as well as the appropriate prevention and treatment. We therefore conducted this study to determine the incidence, characteristics and risk factors of CPSP in elderly patients at both 3 and 6 months after surgery.Elderly patients (aged ≥ 60 years) undergoing elective surgery in our institution between April 2018 and March 2020 were prospectively enrolled in this study. Data on demographics, preoperative psychological well-being, intraoperative surgical and anesthesia management, and acute postoperative pain intensity were collected. At 3 and 6 months after surgery, patients received telephone interview and completed the questionnaires regarding chronic pain characteristics, analgesic consumption, and interference of the pain with activities of daily living (ADL).A total of 1065 elderly patients were followed up for 6 postoperative months and included in final analysis. At 3 and 6 months after operation, the incidence of CPSP was 35.6% [95% confidence interval (95% CI) 32.7 − 38.8%] and 21.5% (95% CI 19.0% − 23.9%), respectively. CPSP cause negative impacts on patient’s ADL and most particularly on mood. Neuropathic features were found in 45.1% of the patients with CPSP at 3 months. At 6 months, 31.0% of those with CPSP reported that the pain had neuropathic features. Preoperative anxiety , preoperative depression , orthopedic surgery , higher pain severity on movement within postoperative 24 h  were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery.CPSP is a common postoperative complication in elderly surgical patients. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population. Chronic postsurgical pain (CPSP) is defined as pain lasting ≥ 3 postoperative months by International Association for the Study of Pain (IASP), which is not otherwise relevant to pre-existing problems or post-surgery complications . The CPSOn the other hand, populations are getting older across the globe. Older adults (aged ≥ 60 years) are the fastest growing section of the population and individuals in this age group undergo surgery more frequently than those in younger age group . The eldWhile the incidence and characteristics of postoperative acute pain in the elderly has been widely studied, only few, and mostly retrospective studies emphasized on CPSP in elderly patients –20. FurtThe purpose of this prospective study was to identify the CPSP incidence in elderly patients at both 3 and 6 months after operation. We also intended to clarify the neuropathic component of the pain, to assess its interference on individual activities of daily living (ADL), and to determine the risk factors of chronicity of postoperative pain.This study was approved by the hospital Ethics Committee of The First Affiliated Hospital of Chongqing Medical University, China. Written informed consent was obtained from all of the participants. Patients aged ≥ 60 years with American Society of Anesthesiologists (ASA) status between I and III, ability to understand the information sheet, undergoing elective surgery in our institution between April 2018 and March 2020 were enrolled in this study. Patients with previous diagnosis of stroke and/or dementia, day case surgery, cardiac or intracranial surgery, or inability to complete a personal or telephone interview, major uncorrected vision or hearing loss, or major psychiatric disease were excluded. An appropriately trained clinical research assistant (CRA) who did not participate in perioperative management of the patients assisted the main investigators with subject enrollment and follow-ups.After admission, the CRA made a face-to face interview with each participant. The questionnaire included items regarding age, sex, weight, height, living situation, preoperative pain at the site of later surgery or elsewhere, current smoking status, and pre-surgical comorbidities including diabetes, hypertension, cardiovascular disease and osteoarthritis.Psychological well-being of the participants was assessed by with Chinese version of Hospital Anxiety and Depression Scale (HADS) . It is aOn the surgical day, data on the anesthetic  and surgical procedures (type and duration) were collected. On postoperative day 1and 2, acute pain during both rest and movement were evaluated with numerical rating scale (NRS) ranged between 0 and 10  every 12 h. The average pain severity within postoperative 24 h was calculated.The same blinded CRA conducted telephone follow-up interviews at 3 and 6 postoperative months. Patients were inquired whether they had any pain in surgical area and if the pain developed postoperatively. If subjects answered with a ‘no’ to any of the two questions, those patients were classified as cases without CPSP. Contrarily, if subjects answered yes, they were considered CPSP cases. For those patients reporting pain, additional measures were used, which focused on the assessment of CPSP characteristics.We adopted the Chinese version of Brief Pain Inventory-Short Form (BPI-SF) to assess the features of CPSP . BPI-SF The intensity of rest pain and movement pain during the past week of the interview was measured by NRS score. Pain intensity was divided into no pain (0), mild (1–3), moderate (4–6), and severe (7–10). Then, the subjects were inquired about pain frequency, location, and pain medication. The NRS score was employed to assess 7 aspects of pain interference with the ADL including general activity, mood, walking ability, normal work, relations with others, sleep, enjoyment of life .In addition, patients with CPSP also completed the Chinese version of Douleur Neuropathique 4 questions (DN4) questionnaire to evaluate neuropathic features of the pain. The DN4 questionnaire is an instrument to evaluate the neuropathic component of chronic pain in adults. It comprises 3 items regarding category of pain including burning pain, cold pain, electric shock pain; 4 items regarding accompanied manifestations including tingling, pins/needles, numbness, itching; 2 items regarding the co-existence of numbness on contact or pinching, and 1 item regarding the initiation or aggravation of pain on rubbing . Items fThe primary outcome of this study was the incidence of CPSP at 3 postoperative months. CPSP was defined as the pain developing after surgery in or near the surgical location and last for ≥ 3 months (NRS score of > 0).Secondary outcomes were the incidence of CPSP at 6 postoperative months, pain intensity, pain interference with ADL, and incidence of neuropathic pain at 3 and 6 months.The sample size was calculated according to the assumption that at least 10 cases were required to test every potential independent variable included in a multivariate logistic regression . Based ot-test, and categorical variables were compared using Chi-squared test. After univariable analysis, variables were taken into multivariate logistic regression when P < 0.20 to determine the independent risk factors for chronic pain. Odds ratio (OR) and its 95% confidence interval (95% CI) were calculated to identify the impact of each variable on the development of CPSP. SPSS v.18.0  was used for data analysis. A P-Value of < 0.05 was considered as statistical significance.Continuous variables were presented as mean ± standard deviation (SD). Categorical variables were shown as numbers (percentages). Between CPSP and non-CPSP groups, continuous variables were compared using independent samples During the 24-month study period, 1593 patients were assessed for eligibility, of which, 86 patients declined participation and 105 patients were not eligible for this study. The main causes of ineligibility were discharge on the surgical day, cognitive/hearing/vision deficit, or inability to understand the study. Of the 1402 patients, 90 dropped out during inpatient follow-up, 158 and 89 cases lost follow-up after 3 and 6 months, respectively. As a result, 1065 patients completed the whole follow-up period  and 229 patients  reported having chronic pain, respectively. Following urological, breast, thoracic, general, and orthopedic surgery, the incidences of CPSP were 27.7% (43/155), 38.3% (23/60), 34.8% (55/158), 26.6% (94/353), 48.4% (164/339) at 3 months, and then decreased to 14.8% (23/155), 25.0% (15/60), 20.9% (33/159), 14.2% (50/353), 31.9% (108/339) at 6 months, respectively. Data on pain intensity, frequency, analgesic consumption, pain interference with ADL, and as well as incidence of neuropathic pain in the individuals with CPSP are shown in Table At postoperative 3 and 6 months, chronic pain significantly interfered with ADL of the patients. The patient’s mood was affected by the pain most frequently. Approximately 40% and 30% of the patients with CPSP reported that their mood was influenced by the pain at 3 and 6 months, respectively. CPSP seemed to have the least influence on normal work of the patients. Only about 20% and 15% of them complained that the pain influenced their normal work at 3 and 6 postoperative months (Table Table P < 0.20).Table The multiple regression analysis indicated that preoperative anxiety, preoperative depression, orthopedic surgery, higher pain severity on movement within postoperative 24 h were associated with a higher risk for CPSP independently at both 3 and 6 months after surgery. In addition, general anesthesia was one of the risk factors for CPSP at 6-months postoperatively  3 months following surgery. Six months later, 21.5% still complained of pain. Our study confirms that CPSP is common in elderly patients with a comparable incidence reported in previous studies. A multi-center retrospective study reported an incidence of 27.2% in patients aged > 65 years 6 months after hip arthroplasty . A recenWe found that majority of the CPSP patients experienced mild rest pain, and no patients underwent severe rest pain. Moderate-to-severe movement pain was common at 3 months after surgery, and then decreased obviously at 6 months. The intensity of the chronic pain in our study was comparable to other research . HoweverChronic pain in the elderly could result in greater postoperative functional disability and poorer quality of life. Herrick et al. showed that moderate-to-severe pain was associated with difficulty in ADL 3 months after hip fracture repair in elderly patients . Our stuThe CPSP development is believe to be relevant to neuropathic mechanism involving nerves damage during surgery, and as well as neuroplastic changes after injury –35. RediMultiple perioperative risk factors of CPSP have been identified in non-age-stratified cohort studies, including biological factors , medical factors , and psychological factors  , 33. In It has been widely studied that negative moods including anxiety and depression are relevant to reduced impacts on descending pain-inhibitory systems, enhancing spinal nociception and pain , 42. TheIn the present study, patients undergoing orthopedic surgery had a high risk for CPSP. CPSP was found in 48.4% and 31.4% of the patients at 3 and 6 months after orthopedic procedures, respectively. Orthopedic surgery is often conducted because of pain, and preoperative chronic pain may confound the result. In this study, the multivariate analysis results indicated that orthopedic surgery patients were nearly 2.5 times more likely to develop CPSP than urological surgery patients after eliminating the impacts of confounders like preoperative pain. Our results are comparable with those of Fletcher et al., who showed that patients underwent orthopedic surgery had an about 3.4 times higher risk of CPSP than those underwent visceral surgery .Consistent with previous studies conducted in adult and pediatric patients , 18, 39,In this study, patients undergoing general anesthesia had a higher risk for CPSP at 6 postoperative months than those undergoing regional anesthesia. Regional anesthesia can be used as a tool in the prevention of CPSP because it has been proved to reduce the excitability of neurons involved in peripheral nociceptive pathways , 50. SevWe did not find independent associations between age, sex, preoperative pain at surgical site or pain elsewhere and CPSP. Although younger age, female sex, and preoperative pain are demonstrated as risk factors for CPSP in several studies , 54, 55,Our study has several limitations. First, this is a single-country and single-site study, which limits the generalization of conclusions and compromises its external validity. Second, the information on CPSP were collected according to self-reporting of the patients by telephone interview, which may not avoid misinterpretation completely. Nonetheless, the follow-up interviews after discharge were undertaken with full caution to guarantee sufficient understanding of the answers and adequate control over the potential misunderstanding about the development of CPSP. Furthermore, we did not confirm the neuropathic characteristics of the pain reported by the subjects with physical examinations or quantitative sensory experiments, which might underestimate patients with clinician-diagnosed neuropathic pain. Although the present study provides important information about neuropathic features of CPSP in elderly patients, knowledge must be improved by further research on the topic. As the accuracy of screening self-questionnaires for neuropathic pain is imperfect, more information is needed about the likelihood of development of neuropathic component of the pain. For this, large cohorts with a long follow-up research with a confirmation of the diagnosis by clinical examination or quantitative sensory experiments are mandatory. Third, although around one-third of the patients in this study had a history of diabetes, we did not collected data on neuropathic features of preoperative pain at baseline. Given the comorbidities between diabetes and neuropathic pain, this makes it more likely that pre-existing diabetic neuropathy confounds the rate of CPSP with neuropathic component. Therefore, the potential impact of previous history of neuropathy on the development neuropathic features of CPSP should be further explored. Lastly, this study described CPSP after several types of surgical procedures. This heterogeneity might limit statistical associations and hamper the identification of specific factors.Despite these limitations, our study represented an important evaluation of CPSP in the elderly surgical population. Our findings suggest that great efforts should be taken to improve perioperative management to reduce the incidence of CPSP, especially after orthopedic procedures. In the future, it would be essential to create a multi-disciplinary geriatric pain treatment and prevention program for the elderly individuals at risk of CPSP.In summary, our study indicated that the incidence of CPSP in elderly patients was 35.6% at 3 months, and then decreased to 27.1% at 6 months. Signs of neuropathic pain were reported in 45.1% and 31.0% of the cases with CPSP at 3 and 6 postoperative months, respectively. Preoperative anxiety and depression, orthopedic surgery, and greater intensity of acute postoperative pain on movement are associated with an increased risk for CPSP. It should be kept in mind that developing psychological interventions to reduce anxiety and depression and optimizing the management of acute postoperative pain will be effective in reducing the development of CPSP in this population.


A qualitative evaluation study of the prematurely terminated PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) study was performed. The PELICAN study aimed to examine pain management for localized neuropathic pain (LNP), as epidemiological figures have shown a high percentage of LNP patients in Belgium. The study compared systemic and topical medications according to pain relief, adverse effects, and several measures of quality of life.  Achieving better study patient recruitment through qualitative research. To investigate and determine the causes of the observed recruitment problems in the PELICAN study, pain centers involved in the study as well as nonrecruiting pain centers were included. Furthermore, it aimed to highlight the positive and negative lessons learned from the conducted study and the number of obstacles the team had to overcome.  A qualitative study, using a mixed methods approach, was performed. Multiple pain centers in Belgium completed an online survey, after which a structured interview was conducted to elaborate the responses in more detail. The broad topics of these meetings were feedback about the study, reviewing survey answers, and actions undertaken to enhance recruitment.  Different factors contributed to the low recruitment rate in the PELICAN study, such as limited and late referral from the general practitioners to the Belgian pain centers, insufficient internal referrals from nonpain specialists, lack of specific expertise on LNP in some centers, scarcity of staff, limited reimbursement to administer complex analgesic schemes, overestimation of the patient population, and the reluctance of patients to participate in pain research. Additionally, shortcomings in the implemented study design and the need for more logistical investments were identified. Clinical Trials. This trial is registered with NCT03348735. EUDRACT number 2018-003617-17. The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies. Future studies could support this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase.  Moderate to severe chronic pain occurs in 19% of European adults, significantly affecting the quality of their social and professional lives –5. When https://kce.fgov.be/en/kce-trials/funded-trials/pelican-localized-neuropathic-pain-a-study-to-compare-topical-treatment-versus-systemic-treatment). The PELICAN study aimed to compare two topical analgesic medications (lidocaine and capsaicin patches) with one of the commonly available systemic treatment options, i.e., the anticonvulsant drug pregabalin, for neuropathic pain conditions. The study was designed to compare topical and systemic medications according to the observed improvement in quality of life, pain relief, and occurrence of adverse effects. The study overview of the pragmatic PELICAN trial, as initially conceived including the initial recruitment, is detailed in The PELICAN study was a randomized, multicenter, comparative pragmatic trial that aimed to examine topical versus systemic treatment in adult patients with LNP syndromes. Systemic treatment options are often linked to side effects, whereas the topical route offers significant advantages. Notably, only a small fraction of the dose administered topically reaches the systemic circulation, thereby reducing the risk of systemic adverse effects, drug-drug interactions, and overdose. The Belgian Healthcare Knowledge Center (KCE) funded the PELICAN study under their KCE Trials program  at week 6. This absence of significance in the primary endpoint was expected due to the small number of patients. The lidocaine plaster group showed improved quality of life and pain relief during the initial phase of the trial, whereas the capsaicin-treated patients exhibited the improved quality of life and pain relief later in the trial. Although a limited number of patients were recruited, the demographic data corresponded with those of previous studies on peripheral neuropathies. This can be regarded as a confirmation of the study protocol validity and applied inclusion process.Recruitment for the PELICAN trial commenced in December 2018. Unfortunately, the recruitment of patients was extremely slow, and despite several actions to address this, the enrollment rate remained insufficient. Finally, and in mutual agreement, the project funder and sponsor decided to stop the trial on March 30, 2020, because of these inclusion difficulties and the COVID-19 pandemic. By the time of the study's premature closure, 32 patients had signed the informed consent form and had been randomized into 10 of the participating centers. All data have been registered in a synopsis report which can be accessed at One of the most challenging findings was the high discontinuation rate observed in both topical treatment options by week 26 (100% for lidocaine and 77.8% for capsaicin). This finding was unexpected, and unfortunately, the premature discontinuation of the trial prevented us from further identifying possible explanations for this finding. Regarding the observed safety profile, systemic treatment with pregabalin appeared to induce more adverse events than lidocaine treatment. Interestingly, the topical application of capsaicin patches seemed to also induce a substantial number of systemic adverse events.Despite the observation of some interesting trends, in the end, there were insufficient data to draw any conclusions from the study, creating the need for a follow-up qualitative study to investigate the reasons for the unanticipated failure of this well-prepared trial. The funder and study team's main aspiration was to determine the reasons behind the recruitment failure through a scientifically based methodology. When a clinical trial is prematurely discontinued, it is essential that stakeholders take the right steps to ensure that lessons are learned, and trust in clinical research is maintained. However, this is often overlooked, leading to a lack of evidence on how recruitment failure occurs and its prevention. A recent study that investigated this delicate matter concluded that the decision to publish findings from a discontinued clinical trial should not rest solely on individual investigators but rather should be part of a systemic approach .A qualitative research project was conducted after the comparative trial was terminated. An explanatory sequential research design was hereby applied, in which quantitative data collection and analyses occurred first, followed by qualitative data collection and analyses –10. Thishttps://nl.surveymonkey.com/r/6NDCY7Q). The content of the questionnaire was beforehand validated for completeness by three members of the study team. After that, an expert panel of four independent judges  conducted content validity and reliability testing to assess the validity of the survey. To strengthen the overall validity of the survey, the experts paid special attention to the inclusion of concurrent  and predictive validity measures  [n = 15). Answering all of the questions was mandatory to complete the survey. Instructions to correctly fill out the form were provided. Reminders were sent out twice (if no response was obtained earlier) to urge the centers to complete the survey. Within 8 weeks of the initial sending of the survey, completed questionnaires were obtained from all participating centers but one. After the completed questionnaire was received and responses recorded, an appointment was scheduled for an interview to discuss the responses and expand on these in more detail with the center's PI.An easy-to-fill online questionnaire was created and consisted of 25 items (for an example see: ination) , 12. FinThe digital survey see  consisteA slimmed-down version of the survey was also sent to accredited multidisciplinary pain centers in Belgium , that had not previously participated in the PELICAN study. Several questions specific to the PELICAN study were hereby omitted, but the more general questions on LNP and its treatment were retained  pain syndromes rather than neuropathic pain alone. Neuropathic pain studies have almost exclusively been limited to either PHN or DPN. This shows that research experience regarding LNP conditions is rather limited in Belgium. Nevertheless, 33% of the responding centers claimed to have previously conducted one or more LNP-specific studies. Most research experiences were in the context of pharmacological studies, and these studies were dated to at least 3 years ago. In addition, two-thirds of the responding pain centers claimed to have experience in conducting pragmatic trials, but during the interviews, it became clear that while pragmatic studies are well known, some studies are mistakenly defined as pragmatic by investigators. Therefore, actual experience with pragmatic studies is lower than initially assumed.Another possible reason for the low recruitment lies in the nonavailability of dedicated study staff. Sixteen of the responding pain centers declared that they had specific staff available to conduct clinical trials. However, it was discovered that this availability was mainly on a part-time basis. The other centers, however, did not have any dedicated study staff. This is understandable considering the small number of algology (pain treatment) clinical studies recently conducted, but this significantly negatively impacts the recruitment of patients in clinical studies.Furthermore, it became clear that many centers have no specific treatment protocols available for LNP. When different options were presented during the digital survey, 83.33% of the responding pain centers identified the following flowchart as their first-choice treatment approach for LNP conditions: (1) systemic medication , (2) topical treatment, (3) infiltration, (4) neuromodulation, and (5) spinal administration of analgesics. The different flow charts that were proposed for review are detailed in Recruitment appeared slow from the outset and relied primarily on internal referrals. This raises the question as to why there are so few external referrals to pain centers. Interviews revealed that general practitioners (GPs) tend to treat LNP complaints themselves, mostly applying systemic treatment options . Thus, many patients had already completed pregabalin treatment before referral to the pain center, impacting their inclusion into the study protocol. In addition, patients tend to remain in primary care or related specialties for a longer period, so late referral also contributed to the low recruitment rate, with many patients falling outside the set time frames for the duration of pain symptoms. Such a high level of late referral had not been anticipated by the PELICAN study team or local investigators during the feasibility studies.Notably, 50% of the patients who were prescreened refused to participate in the study—higher than initially anticipated—due to patients' apprehension about financial implications. This is because, initially, only the systemic option  was reimbursed. During the recruitment period, the high concentration capsaicin patch, was reimbursed. Patients could now choose a fully reimbursed topical treatment option, causing a significant number of patients  to become reluctant to participate and rather “safely” opt for the reimbursed capsaicin treatment.Participating centers also mentioned insufficient reimbursement for nursing activities related to the application of the concentrated capsaicin patches. Treatment with topical capsaicin requires a significant time investment from pain nurses, without any compensation or lump sum reimbursement. Although a substantial additional compensation was provided by the study protocol for the execution of capsaicin treatment by the funder, this was still perceived as too little by some participating centers. Undoubtedly, this had an additional negative impact on recruitment. Interestingly enough, a similar situation has arisen in routine clinical practice. After the capsaicin patches were reimbursed by the social security system in Belgium, uptake in clinical practice remained limited due to nonreimbursement for nursing activities. The main reasons for recruitment failure in the PELICAN study are described in more detail in A specialized monitoring system was developed so that patients and investigators could submit all data and assessments related to the PELICAN study digitally. The PELICAN@home platform—a primary source—was hosted on servers within the central server facility at the Antwerp University Hospital. During the trial, feedback was received from participating pain centers that some patients faced difficulties in completing the digital assessments. Therefore, the study team ensured that all assessments were also available on paper (even in different languages). Nevertheless, during the digital survey, half of the PIs described the digital solution as too complex. The other half rated the digital platform as rather difficult (16.7%) or acceptable (33.3%). No PI rated the PELICAN@home as user-friendly. From the patients' perspective, a slightly different picture emerges as no one considered the platform to be too complex. Therefore, the digital platform was considered quite complex by and for the patients, but within acceptable standards. Although it was not clear from the survey that using the digital platform caused anxiety in patients, pilot testing of the user-friendliness of implemented digital solutions must be considered in future trials.Topical treatment of LNP is underutilized in clinical practice. This should be viewed against the background of less attention paid to the application of less invasive pharmacological versus the more invasive treatment options within the pain center.Referral of patients suffering from LNP  from primary care to multidisciplinary pain centers is slow and often occurs only after other specialties have been repeatedly consulted. Acute or subacute pain syndromes are rarely observed in tertiary pain centers. Therefore, future studies in this field should be firmly anchored with primary care to enroll these patients on time.Some study protocol-related criteria negatively impacted recruitment .Finally, some pain patients, as well as caregivers, proved to be less digitally savvy than expected, so a paper backup system had to be provided.Four primary reasons for the slow recruitment rate were identified in the qualitative study as follows:A majority of patients with neuropathic pain suffer from LNP. Based on the International Association for the Study of Pain (IASP), LNP is described as a type of peripheral neuropathic pain characterized by consistent and circumscribed area(s) of maximum pain associated with abnormal sensitivity of the skin and/or spontaneous symptoms characteristic of neuropathic pain , 15. By Regarding the initiative on methods, measurement, and pain assessment in clinical studies, several outcome measures, corresponding to six domains, have been recommended for assessment in pain trials: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, and (6) participant disposition. However, since many treatments often only provide meaningful pain reductions in 40%–60% of patients, other outcomes such as physical, social, and occupational function are sometimes considered to have comparable importance . TherefoHowever, the results of the preliminary literature review on LNP revealed a lack of conclusive research concerning topical therapeutic options. A limited number of studies discussed and compared the efficacy of each of the topical treatments with that of a placebo. However, a 2014 systematic review of topical lidocaine for neuropathic pain (involving 280 patients with PHN) showed very low-quality evidence of the efficacy of topical lidocaine owing to small sample size, incomplete outcome assessments, and modest outcome measures of efficacy. Other clinical trials have found that 5% lidocaine patches are effective and well-tolerated for treating PHN with minimal toxicity risk or drug-drug interactions , 19. A rThe capsaicin dermal patch delivers a high concentration (8% w/w) of synthetic capsaicin, a highly selective agonist of transient receptor potential vanilloid-1 (TRPV-1), directly to the site of pain. The 8% capsaicin dermal patch is indicated in the European Union (EU) for the treatment of peripheral neuropathic pain in adults, either alone or in combination with other medicinal products . In the Considering the current lack of solid scientific evidence, the findings of the PELICAN study would have provided valuable and unique information regarding the comparison between systemic and topical medications. Despite the extensive preparation and review of the final study protocol, the PELICAN study had to be discontinued due to the low recruitment rate. Some possible primary causes were revealed during the qualitative study, but it is also necessary to critically assess the reasons for the termination of the PELICAN study considering the observed findings in other unsuccessful studies.Failure to enroll sufficient participants in a trial has been a long-standing problem . An overIn the PELICAN trial, recruitment appeared slow from the outset and relied primarily on internal referrals . Although educational material and flyers were kept at the disposal of the pain centers, it remained difficult to substantially increase the volume of internal referrals in all participating centers. In addition, the study team quickly observed that almost no patients were referred to the participating pain centers by primary care practitioners. It is commonly known that most chronic pain patients are treated by GPs. The previously mentioned large-scale European pain survey by Breivik et al. indicated that most pain patients (70%) are treated by GPs and 27% by an orthopedic specialist. Only 2% of chronic pain patients were treated by a pain management specialist. Most respondents (69%) had been treated by the same physician for 1–15 years. When explicitly asked whether they had ever been to a pain management specialist, 23% of patients (mean) responded affirmatively. This percentage, however, differed significantly throughout Europe, ranging from 8% in Norway to 40%–43% in France, Israel, and Italy. It is obvious that every pain-related study must involve GPs in the inclusion of patients and to enable timely referral of sufficient numbers of pain patients. Failure to actively involve GPs in the design and execution of the study protocol will significantly compromise a successful recruitment strategy.Efforts were made to address the recruitment issues: a substantial number of GPs in all geographical parts of Belgium received a letter explaining the trial, patient flyers were provided for the waiting room, the trial was made public via a website and social media, and the study team presented the PELICAN study on different occasions to both pain and nonpain colleagues. Unfortunately, none of these efforts had the desired results since no impact could be observed on the recruitment rate.After discussing this lack of recruitment with the participating clinics' representatives, the PELICAN study team revised the target sample number. The feasibility report elaborated on each center's capability to recruit patients and the period needed to accomplish this. Later, the report was discussed again with the investigators, who agreed on the selected target, yet the slow recruitment rate still did not improve. Thus, there was a considerable gap between the actual and intended patient numbers. Therefore, overestimation could have played a role in this study. It is crucial to properly understand how large the corresponding patient population is, how many people are needed in this population, and how many will participate. This is where many investigators overestimate the number of patients to be ultimately included in their trial .The inclusion and exclusion criteria are important for the reliability of medical trials. Very restrictive criteria cause willing patients to be excluded for not fulfilling the trial's essential criteria. Likewise, some of the inclusion and exclusion criteria applied in the PELICAN study may have affected the number of patients included in the study. It became evident that pain duration was often prolonged in patients who were prescreened for inclusion in the PELICAN study. Unfortunately, this is in accordance with general epidemiological findings. Breivik et al. showed that only 12% of respondents have suffered from pain for <2 years, almost 60% between 2 and 15 years, and many (21%) had lived with pain for ≥20 years, with an overall median pain duration of 7.0 years . ConsideAnother protocol-related criterion that negatively impacted recruitment was related to the exclusion of previous treatment with gabapentinoids. This proved to be especially critical as the study started from pain management clinics and not from general practices. Considering the common treatment trajectory of patients with pain, many had already been introduced to analgesics and antineuropathic drugs and were therefore no longer eligible for enrollment. Primary care physicians are accustomed to using anticonvulsant drugs in patients with suspected neuropathic pain conditions. Due to the restrictive nature of the study protocol, even a short-term trial therapy with an anticonvulsant immediately resulted in exclusion from the PELICAN study, even if no topical treatment had previously been tested. In the future, one should consider implementing changes to the inclusion criteria for analgesic trials so that short-term negative trial treatments can be discarded based on several predetermined criteria such as duration of trial treatment, the maximum dose administered, and occurrence of side effects. Such an approach would increase the number of patients eligible for inclusion in the study protocol.We should ask ourselves whether recruitment failure could have been prevented. Briel et al. stated that the most common reasons for recruitment failure seem preventable in a pilot study that applied the planned informed consent procedure . This waAnother reason for recruitment failure in the PELICAN study could be linked to the irregular medical follow-up by chronic pain patients. This was mentioned in several interviews during the qualitative study and is confirmed by the findings of previous studies. Breivik et al. in their European survey on chronic pain delved more closely into the number of patients' visits to doctors. The interviewers asked participants how many times in the last 6 months had they visited their primary treating physician for their illness or medical condition that caused pain. Reportedly, 16% had not visited their physician at all, 14% had visited only once, 60% had visited two to nine times, and 11% had visited at least 10 times in the last 6 months. Of the respondents, 35% had consulted one single physician, while 54% had consulted two to six different physicians during the same time frame . This meSeveral concerns were raised regarding several digital aspects of the study. Digital health has become more important, especially since the COVID-19 pandemic, but it should be implemented with a lot of considerations for patients as well as for the supporting study staff. Half of the responders from the participating pain centers believed that using the digital platform for the follow-up of the therapeutic response and adverse events caused anxiety in some patients or even dissuaded them from (further) participation. This feedback is of major concern for the study team and is somewhat unexpected since the application of a similar digital platform in previous pain-related studies was well received by patients , 42. Addhttps://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/) regarding post-trial provisions. This would allow for successful treatments to obtain regular reimbursement based on the study findings, while economically fragile patients would be assured that they would never have to pay the full cost of treatment.Patients may experience out-of-pocket costs when participating in a clinical study, including transportation costs and lost work as well as medical costs for additional testing or interventions. Insurance or social security may not cover medical care beyond what is deemed evidence based. Even when medical care is covered, deductibles are often relatively high, and a patient may not be able to afford participation. Notably, patients' fear of having to pay for the costs themselves after the study ends significantly hampered their willingness to participate in clinical trials . Pain paOne additional comment should be made regarding the capsaicin treatment that could have negatively impacted patients' willingness to participate in the trial. Patients are unfamiliar with capsaicin as a therapeutic agent . The 1 hInvestigators should also carefully consider which study method is the most appropriate to obtain the necessary information. Qualitative surveys, like the one we performed, are an often-used possibility, but one should also consider the performance of Delphi studies. Surveys have been performed in several countries to investigate some major pain-related issues –54. In IFinally, there is also some critical discussion outlining the role and possible benefits of social media in augmenting and supporting the original methods of recruitment. Reuter and Lee investigated this matter and concluded that, mostly, social media has complemented rather than replaced traditional recruitment efforts . NeverthAll the abovementioned findings are essential to be taken into consideration in future pain studies. Given the extremely low number of drugs currently approved for pain treatment, it is crucial to address all barriers to recruitment to allow new therapies to be successfully validated in completed clinical trials. For instance, the same remarks have been formulated for studies related to head and neck cancer .On the positive side, the topical administration of capsaicin has become more widely known within pain centers because of their participation in the PELICAN study. Moreover, in half of the participating pain centers, participation in the PELICAN study was used to facilitate the clinical diagnosis of LNP.The participating pain centers considered low enrollment in the PELICAN study, mainly due to insufficient (timely) referral from primary healthcare providers and other specialties, to be the main issue leading to the study's premature cessation. Additionally, poor recruitment was also attributed to the too strict inclusion and exclusion criteria—limiting the inclusion of many patients with neuropathic pain. Third, the reimbursement of high-concentrated capsaicin patches, which was granted after the initiation of the PELICAN study, undoubtedly further reduced the inclusion rate. Patients opted for the reimbursement treatment option rather than going through the burden of the study protocol and uncertainty about the follow-up treatment after the study completion.Topical treatment of localized neuropathies often remains (somewhat) unknown .Topical treatment modalities are inadequately used in clinical practice because of reimbursement modalities. This has significantly hampered the introduction of such treatment modalities in routine clinical practice.Faster detection and referral of patients with LNP from primary healthcare providers or other medical specialties to specialized pain centers.Direct inclusion of patients from primary healthcare providers with the active participation of GPs in the development of protocols and recruitment.Training primary healthcare providers and physician specialists to make correct diagnoses (recognition of pain syndromes such as LNP).A better description of the distinction between subacute pain syndromes and chronic pain syndromes and possibly including the two separate cohorts in a future study protocol.Better support should be provided for pain centers with a less well-developed study team, with consideration given to possible financial reimbursement for nursing actions as part of the study.Fundamentally, the problem of an unbalanced focus on invasive treatment techniques versus pharmacological or noninvasive treatment options arises. This is undeniably linked to the underlying funding systems—or lack thereof.Further, simplified and rationalized digital platforms and tracking systems and accommodation of the still significant digitally illiterate group.Need for innovation in pain treatment. There is concern regarding the lack of development of new therapeutic agents or approaches to acute and chronic pain. Therefore, there is a lack of experience in performing applied research in pain centers.Based on the findings of this qualitative study, 10 points should be considered important for health policy at the national level as well as for future studies within the specialism of pain treatment as follows:The findings of the qualitative study demonstrate the need for further, more varied LNP research in Belgium, not limited to pharmacological studies. It also sheds important light on the recruitment obstacles that may be faced during these studies, which can be overcome in subsequent research by using or at least considering some of the information presented in this paper. Support programs by study sponsors might be helpful for investigators involved in discontinued trials and promote transparency and learning lessons for future studies. Furthermore, our qualitative study explores the various methodologies that may help recruit patients and participants ahead of trials. Future studies may aid this research by offering better proposals for feasibility and recruitment, for instance, by designing and conducting a compelling pilot study or applying social media during the recruitment phase.