Bertolotti syndrome is a differential diagnosis in back pain. We know little about it in Uganda. This study aimed to describe the prevalence, clinical and radiological patterns of Bertolotti syndrome and functional disability associated with it.We did a descriptive cross-sectional study at the spine outpatients' clinic of Mulago National Referral Hospital. We screened patients with chronic low back pain for lumbosacral transitional vertebrae over four months and classified them according to Castellvi. We collected demographics, clinical symptoms, and functional disability data and summarized it descriptively.Out of 385 patients, we identified 39 with Bertolotti syndrome. The prevalence and the median age were at 10.1% and 49 years respectively, with most patients being females (66.7%) in the age range of (36 to 50) years, the pain started during the age range of 31–40. The commonest and least were type IIA (20.5%) and type IV (10.3%), respectively. Most patients (66.3%) had radicular symptoms, mainly the toe extension nerve root. The average visual analog scale was 6.3. However, most patients suffered from mild- to moderate disability (66.7%).Bertolotti syndrome is common and functionally debilitating. We should consider it in the differential diagnosis of chronic low back pain. Bertolotti syndrome (BS) refers to pain associated with the occurrence of a lumbosacral transitional vertebra (LSTV). The global prevalence of low back pain is 18.3%Patients commonly present with lower back pain, gluteal pain, S1 radiculopathy, and significant functional disability. Studies have shown that patients with LSTV and LBP have more pain and function impairment than patients without LSTV.Despite the high prevalence of LBP in Uganda, there is little literature about BS. This study sought to determine the prevalence of this syndrome, its clinical presentation, and associated functional disability. The findings will enhance clinician awareness to enable timely diagnosis and management.This was a descriptive cross-sectional study carried out at Mulago National Referral Hospital spine outpatient clinic for four months from November 2019 to February 2020. Approval for the study was by the Makerere University School of Medicine Research Ethics and Committee (SOMREC) and Mulago Hospital Research and Ethics Committee with reference #REC REF 2019-159.Written informed consent was got from all and we followed good Clinical Practice guidelines. Using lumbar spine radiographs, we screened all consenting adult patients with chronic low back pain for LSTV. We classified Lumbosacral transitional vertebrae according to the Castellvi classification.Exclusion criteria included all patients with LBP whose lumbar x-ray images showed fractures, tumors, infection, or other congenital anomalies of the lumbar spine that prevent study because of distortion of the anatomy and those who had undergone spine surgery.Using the Kish-Leslie formula to calculate sample size for means, taking a 95% confidence interval and error margin of 5% as the assumptions, we got a sample size of 389 patients.We consecutively recruited all participants with chronic low back pain who consented and had adequate lumbar spine radiographs into the study until the sample size was attained.They included socio-demographic characteristics, age, sex, and occupation.Clinical presentation of Bertolotti syndrome, including the severity of pain using the Visual analog score.Radiological classification according to Castellvi classificationFunctional disability using the Oswestry disability index.These included:We consecutively screened 389 patients with chronic back pain for LSTV and identified 39 patients with BS using adequate lumbar radiographs done at MNRH using a digital x-ray machine, both lateral and anteroposterior views. The radiological classification of LSTV was according to Castellvi's classificationWe screened patients without LSTV out and didn't subject them to further examination or interviews.We administered a questionnaire and did a physical examination for patients with BS. We inspected the patients for any deformities such as scoliosis and kyphosis. We palpated the lower back for muscle spasms and tenderness. We used the modified Schober's test to test for a range of motion of the lumbar spine.Modified Schober's test involved marking the lumbar spine at the L5 and T12 spinous processes and the distance noted. Then the patients were requested to flex the lower back towards toe touch with knees straight. Then the distance was remeasured in that position using a tape measure. The test was deemed positive if the difference in measurements was less than 4 cm, showing limitation in lumbar flexionWe determined sacroiliac tenderness using the FABER, anterior gapping, and thigh thrust tests. We considered the patient to have sacral iliac tenderness if at least two of the tests were positive.The patient was placed in the supine position. I applied downward pressure and outward to the anterior superior spines bilaterally. The test was deemed positive if the patient complained of pain in the posterior gluteal region.With the patient still in the supine position, the hip was flexed and slightly adducted. Then, a posterior shearing force was applied through the femur onto the sacroiliac joint. Increasing pain showed a positive test.This test involved flexion, abduction, and external rotation of the femur at the hip joint. While holding down the anterior superior iliac spine on the opposite side, the pressure was applied at the medial side of the knee. This elicited tenderness if there was sacroiliac pathology.16We then did a neurological exam to determine sensory and motor deficits. We examined dermatomes for touch and pain using cotton wool and pinpricks respectively comparing opposite dermatomes.It contains ten sections that access a patient's ability to live with back pain and the degree to which this pain is affecting daily life. Each section has scored a maximum of 5 if the last statement is marked. The total score is computed by converting it into a percentage that will grade disability from mildly impaired to crippled.18The score calculated is interpreted as follows.We used STATA version 13 for descriptive statistics and summarized using means or standard deviation (SD) for normally distributed data, medians, the interquartile range for skewed data. The demographic characteristics are presented as frequencies and percentages.Questionnaires and sample data extraction sheets were coded, assigned a unique identifier, and entered into excel after double verification of the entered data.Radiographs photographed and daily backup kept on the cloud, PI's computer secured with a password, external drive, and Google drive. We stored completed questionnaires and sample data extraction sheets under lock and key at the study site. Back-up was performed daily.A total of 39 out of 389 participants screened had Bertolotti syndrome. (10.1%) The majority were female 26/39 (66.7%). Those aged between 36 to 50 were 17/39 (43.6%) with a median age of 49 years. 14/39 (35.9%) were not employed. 12/39 (30.8%) patients had the age of onset of pain between 31 to 40 years.The majority (95%) of patients reported axial pain with 66.7% of that being in the midline. We found radicular pain in 66.7% of patients and the majority (57.7%) had pain in the right lower limb. Almost half (45.5%) of patients had severe axial pain, while most patients had mild radicular pain (40.7%). Most patients had pain lasting over 19 hours of the day. (46.1%).The majority (94.8%) had no lumbar spine deformity and the range of motion of the spine was limited in 71.8% of the patients according to a positive Schober's test. Some patients (23.1%) had muscle spasms on clinical examination.In addition, most patients had tenderness in the midline of the lower lumbar spine at all the affected levels (mean 71.7%) but more especially at L5 (66.7%) while the right lower back was the next most reported site of tenderness at the S1 level (25.6%). Sacroiliac tenderness was more common on the right.The commonest dermatome affected by sensory deficits was L5 on both sides and the least affected was L3. Also, 90% of patients had sensory deficits.Then also 20% of patients had weakness in the lower limbs, especially the L5 nerve root in 20.8% of the patients. The next commonly affected nerve root was S1. Only 8% of patients had a severe weakness, with power less than 3/5.Furthermore, 51.3% of patients had moderate disability according to the Oswestry disability index, with 12.8% being crippled by pain. Also, the commonest type of LSTV was type IIA, affecting 25.6% of the patients followed by type IIB and the least type was IIIA at 5.1%. Overall, type I has 25.6%, type II 46.1%, and type III with 25.6%; making type II the commonest type of LSTV in this study.There is a paucity of information on the prevalence of Bertolotti syndrome in the world, especially in developing countries. Most of the data is from estimates of smaller hospital-based studies. In Sub- Saharan Africa, the prevalence of Bertolotti syndrome in the population is unknown. This could be because of the lack of African literature about itThis study has attempted to describe the clinical patterns of patients with BS and we found the prevalence to be 10.1%. This is higher than the global reported prevalence in other studies done in the general population at 5–7%.23Most patients were aged between 36 -50; with an average of 45.8 years. This is within the range of most studies The majority in this study had tenderness in the axial spine, paravertebral region, buttock, and leg pain. This correlates with other studies in which low back axial pain was the most significant site of tenderness, followed by lumbar - buttock painRadicular pain was found in the majority of patients, especially the right lower limb. This correlates with other studies which reported up to one-third of cases.This study found that half of the patients had severe axial pain, with the majority having mild radicular pain. The average VAS for both radicular and axial pain was moderate pain. This compares to some studies.Most patients had pain lasting most of the day. This is comparable to findings by Morin et al. in which patients had pain most of the day and for over three years. The present study showed that the majority had scoliosis on both examination and radiology. This agrees with several studies. Jain et al. reported that 100% had scoliosis. We found that the range of motion of the spine was limited in some patients and most had no muscle spasms on clinical examination. This is similar to most studies Almost all patients in this study had sensory deficits. The commonest dermatome affected by sensory deficits in this study was L5 on both sides and the least affected was L3. Weakness in the lower limbs was uncommon, affecting L5 and S1. This is similar to other studies.The study found that the clinical presentation of BS is like that of other causes of back pain except that it occurs in a younger age group, is more refractory to treatment. It needs a high index of suspicion to consider it in the differential diagnosis.The key LSTV associated was type IIB.Many types of LSTV were found in the study, with type II the commonest. Also, the commonest subtype of LSTV was type IIA. These findings are comparable to other studies.Overall, in this study, most patients had moderate- to severe disabilities. This is comparable to the average disability found in other studies. These patients also had undergone more workups and had worse physical and mental health scores.Bertolotti Syndrome is a common condition that goes unrecognized, undiagnosed, untreated for long leading to severe functional disability. It affects a younger age group than other causes of back pain and presents with closely similar symptoms but with worse pain and disability.We recommend that Bertolotti syndrome should be suspected and screened for among patients presenting with refractory low back pain.Future research should explore pain generator identification using advanced imaging and finding specific treatment modalities for this condition.Finally, a comparative study should be done between patients with BS and those without to determine differences in response to treatment.


CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity  by improving pain relief , increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events  and 42% opioid dose  as opposed to usual prescribing arm. The final health utility score was significantly higher  by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the  Treatment of moderate to severe nociceptive chronic pain requires a multidisciplinary approach, in which opioid analgesics continue to be standards of care. Given the chronic pain and mental health overlap, growing concerns about the opioid epidemic, and lack of data that support the use of opioids for long-term pain management, new treatment approaches are needed . In the CYP2D6, OPRM1, and COMT  vs. 0.71 p < 0.05) [0.58–0.82]) compared to the PGx-guided arm, and required 42% higher morphine equivalent daily dose (MEDD) .p < 0.05). For mental health, the PGx-guided arm showed a significant reduction in anxiety values , and an improvement in the Short Format Health Survey 12 (SF12) results , which evaluates the physical component of health, meanwhile any significant difference was observed in usual care arm.p < 0.01) in the PGx-guided arm vs. the baseline visit, as seen in p < 0.001), with less than 23% prevalence for sleepiness  = 0.06 [0.003–1.07]); 30% prevalence for nervousness  = 0.17 [0.040–0.75]); 34% prevalence for headache  = 0.15 [0.030–0.62]), and 27% prevalence for constipation  = 0.24 [0.062–0.93]) as opposed to the usual care arm. A 32% lower prevalence of dry mouth was also observed  = 0.22 [0.060–0.78]), although this significant difference also appeared at the baseline visit . Insomnia , sleepiness , and depression  improved upon the final visit.A reduction was observed at 3 months in the total number of adverse events (AEs) , and those who used illicit drugs or medical cannabinoids, were excluded from participating in the study. Other important factors were not controlled in this study, such as female predominance, pain duration, or variables such as body mass index (MEDD was not adjusted according to body weight), testosterone/estrogen levels, or other lifestyle influences. They could have all interfered with the occurrence of pain experience and analgesic response. In this situation, they could have independently influenced the recorded side effects and should be considered in future studies.A clinical trial was designed and developed at the pain unit (PU) of the Alicante Health Department of the Dr. Balmis General University Hospital, Spain, from October 2021 to April 2023, with patients referred to from six primary care centers. Sixty patients with CNCP (47 women and 13 men) were included. The inclusion criteria were adults aged ≥ 18 years with CNCP who required opioid analgesic treatment and signed informed consent. Patients under 18 years with oncologic pain or any psychiatric disorders that could interfere with properly conducting this study were excluded. This study did not incorporate other chronic pain conditions of unknown pathophysiologies, such as fibromyalgia or neuropathic pain conditions, such as painful polyneuropathy, postherpetic neuralgia, trigeminal neuralgia, and post-stroke pain. The study flow chart is shown in CYP2D6, OPRM1, and COMT genes were used to guide opioid treatment , which allow medical diagnoses, outcomes, and medication use to be reviewed. When participants enrolled in this study, saliva samples were collected for the pharmacogenetic analysis. Approximately 2 mL of saliva was collected in tubes containing 5 mL of PBS. These tubes were rigorously identified and sent to the laboratory for next-day genotyping. Here the researchers randomly allocated patients to one of the two arms using the clinical trial management software OxMaR (v2014). They reported only the genotype of the patients in the PGx-guided arm to clinicians and indicated any variants that could influence opioid management. The reatment . This inAll the patients were interviewed upon the baseline visit to assess their physical health and medical history. Validated scales and questionnaires were completed during the baseline and final visits (after 3 months of opioid treatment). All the questionnaires were self-administered but supported by the presence of an expert clinician.https://euroqol.org/, accessed on 15 June 2023). The Short Format Health Survey 12 (SF12), a 12-item questionnaire with a mental  and a physical component score , and a mean of 50 and a standard deviation of 10 in the general US population . Categorical variables are expressed as percentages. The relative frequencies of genotypes were calculated for each group. The observed gene frequencies were compared with expected frequencies using the chi-square test and the Hardy–Weinberg proportion. In all cases, multiple testing was adjusted by the Bonferroni correction method. The demographic, clinical, pharmacological, and genetic data were compared using either the χhe means .Our results support the efficacy and safety of the clinical implementation of genotype-guided CNCP opioid use for pain and comorbid psychiatric disorders management, lowering the risk of iatrogenically induced side effects and opioid dose requirements compared to usual care. Caution and special consideration are needed before administering anxiolytics, particularly benzodiazepines, antidepressants, or neuromodulators, to patients with chronic opioid use due to the high-risk use behavior in general adult populations.


Residual limb neuromas are a significant cause of post-amputation pain. There is little knowledge concerning ultrasound-guided (US) radiofrequency ablation (RFA) as treatment.To investigate US-guided RFA for neuroma associated pain in individuals with limb amputation.The notes of nine consecutive patients were retrospectively reviewed. Information obtained included neuroma size and nerve, RFA duration/temperature, pain scores, analgesic requirements and ease/comfort of prosthetic use. Eight patients had lower-limb amputations and one had a trans-radial amputation. All except one, underwent diagnostic US-guided steroid injection to confirm the neuroma as the source of pain, prior to RFA.Six patients reported significant reduction in pain scores (defined as at least 50% reduction) and an improvement in comfort/ease of wearing their prosthetic limb, with no adverse effects. Three of these six patients also reported a reduction in analgesic requirements. Of the three remaining patients – one had a large sciatic nerve neuroma that was eventually surgically excised, another had confounding pain from an adjacent bony spur, whilst the third patient did not receive a routine diagnostic steroid injection prior to RFA.Our findings suggest that US-guided RFA is safe and effective for small to medium-sized residual limb neuroma associated pain in individuals with limb amputation. It can reduce pain and analgesic requirements, improve comfort/ease of wearing the prosthesis and potentially avoid surgical excision. We recommend patients should undergo a diagnostic steroid injection prior to RFA to confirm that the neuroma is the source of pain. However, it is also recognised that many individuals with limb amputation have neuromas that are not apparently causing pain.3Residual limb neuroma-associated pain can be difficult to treat and is often managed using an interdisciplinary approach with a combination of neuropathic analgesia, physiotherapy, adjustments to the prosthesis, prosthetic counselling and eventual surgical excision.4 Its incidence has been reported in up to 74% of individuals with limb amputation.5 This is different from phantom pain, which has been described as a painful or unpleasant sensation in the distribution of severed limb after amputation. It can be classified as either neuropathic-like  or nociceptive-like  or a combination of both. It has been reported in 85% of patients with limb amputation. 4Neuroma-associated pain could be due to residual limb pain or phantom pain or a combination of both. Residual limb pain  has been described as a sharp, burning, ‘electric shock’-like pain which the patient often attributes to an incision site around the residual limb or perceives the pain originating deep in the residual limb.6Although the mechanism of interaction is not fully understood, residual limb pain and phantom pain often coexist post-amputation and Montoya et al have reported a significant correlation between the severities of these two types of pain in individuals with limb amputation.There is a paucity of studies in the literature concerning ultrasound-guided (US) radiofrequency ablation (RFA) as a treatment for residual limb neuroma pain in terms of its effectiveness in reducing pain and analgesic requirements, improving comfort when wearing prosthetic limbs and reducing the need for surgical interventionThis study aims to investigate the effects of US-guided RFA as a treatment for residual limb neuroma- associated pain. After retrospectively reviewing the patient case notes, we retrieved data on the safety, efficacy, side effects, and complications of US-guided RFA in the treatment of painful residual limb neuroma.The clinical notes and imaging of nine consecutive patients who underwent RFA for residual limb neuroma-associated pain during the period 2015 – 2019 were retrospectively reviewed. Information obtained included:1.Patient demographics2.Site of amputation3.Reason for amputation4.Size of neuroma and nerve involved5.Phantom pain (if any)6.RFA duration, temperature and pulsation 7.Pain  scores – at 3-8 months pre-RFA, immediately pre and post RFA, 1 day, 2 days, 2 weeks and 3 months post-RFA.8.Analgesic requirements pre- and post-RFA9.Adverse effects of RFA (if any)10.Comfort and ease of using prosthetic limb pre- and post-RFA.After obtained the NRS pain scores at the aforementioned intervals, statistical analysis was performed using MATLAB . In order to assess the expected value and variation in pain scores amongst the patients, the mean pain score and standard deviation at the different time intervals (pre- and post-treatment) for all nine patients and for the six successfully treated patients were calculated.In order to determine the statistical significance of the change in pain scores, Wilcoxon signed-rank test was used to calculate the p-values when examining the change in pain scores from initial presentation and the different time intervals (pre- and post-treatment). Wilcoxon signed-rank test was selected because of the small sample size and that pain scores cannot be assumed to be normally distributed.Written informed consent was obtained from each patient prior to the RFA procedure. As this is a retrospective review of past patient notes, ethical approval was not needed.1.The initial assessment in the outpatient clinic of the patients with limb amputation was performed by a Consultant Rehabilitation Physician (DHS) or a senior trainee under the supervision of the consultant at which initial pain scores were taken.2.Through magnetic resonance imaging (MRI), the presence a neuroma was confirmed as well as its site, size and nerve involved.3.The patients were then reviewed again post-MRI scanning by the Consultant Rehabilitation Physician and referred to a single Consultant Musculoskeletal Radiologist (RM) who performed US-guided RFA treatment.4.The patients waited between 3-8 months for their US-guided RFA treatment.5.On the day of treatment, pain scores were taken again before the RFA.6.The patient was placed in a comfortable position . The skin was then prepped with Isopropyl Alcohol solution and draped.7.The linear high-frequency ultrasonic transducer  was covered with a sterile transparent sticker and placed transversely over the area of focal tenderness as reported by the patient.8.On imaging with a high-resolution sonography machine , the presence of the neuroma was reconfirmed on both transverse and longitudinal views by rotating the transducer by 90 degrees. The neuroma was visualised as a well-defined hypoechoic lesion involving the affected transected nerve .9.After attaching to a radiofrequency generator  , a 10 cm10.After undergoing RFA, pain scores were taken immediately post-procedure, via telephone follow up 1 day, 2 days and 2 weeks post-RFA, and via face to face follow up in the rehabilitation clinic 3 months post-RFA. The patients were asked to give the maximum pain score that they felt on the day of assessment.There were 9 patients (3 men and 6 women) aged between 30 and 69 years (mean 45 years). Eight had lower limb amputations  and one had a trans-radial amputation. Four of these patients underwent amputation due to trauma, two due to peripheral vascular disease, two due to neoplasm and one due to infection. The patients underwent amputation between 1 and 26 years ago (mean 7 years).On initial presentation to the outpatient rehabilitation clinic, seven patients reported a pain severity of 10/10 on the NRS score, one had a pain score of 9 and one had a pain score of 7. All nine patients reported pain around the residual limb, and six of these patients also complained of phantom pain in addition to their residual limb pain. The residual limb condition in all these patients was stable with no local inflammation or acute skin or soft tissue changes. All patients reported discomfort and difficulty wearing their prosthetic limb due to pain. Patient demographics, prosth-eses suspension and weight-bearing characteristics, pre-RFA pain and neuroma characteristics are illustrated in Through magnetic resonance imaging (MRI) and ultrasound scanning, three patients were found to have neuromas involving the tibial nerve, three involved the sciatic nerve, one involved the common peroneal nerve, one the superficial peroneal nerve and one the ulnar nerve. The largest neuroma was 30x30mm and involved the sciatic nerve . The smaThe nine patients were consecutively referred from the prosthetic rehabilitation team to the radiology team for consideration for ultrasound-guided RFA. On the day of treatment, pain scores were taken again before the RFA – six patients reported a score 10/10 for their pain, two patients reported a score 8/10 and one patient reported a score 7/10.In all cases, the patient was able to point to a focal area of tenderness over the residual limb that was elicited on direct palpation. In the six patients with phantom pain, palpating over the focal area of tenderness led to a positive Tinel’s sign along the course of the affected nerve in the phantom limb. On direct pressure from the transducer, the pain reported by the patient in all cases was able to be reproduced.After undergoing RFA, pain scores were taken immediately post-procedure, via telephone follow up 1 day, 2 days and 2 weeks post-RFA, and via face to face follow up in the rehabilitation clinic 3 months post-RFA .All patients bar one underwent a diagnostic US-guided steroid injection to confirm that the neuroma was the source of the pain, prior to RFA.Six patients reported a significant reduction in pain NRS scores – defined as at least 50% reduction,7 sustained over at least 3 months with no adverse effects. Three of these six patients also reported a reduction in analgesic requirements, two patients did not have any analgesic pre- and post-RFA and one patient did not report any significant change in analgesic demands. All of the six patients reported an improvement in comfort in wearing their prosthetic limb. Amongst these six patients who reported significant pain relief, three of them also had pre-existing phantom pain and found that RFA also resolved their phantom pain completely.Of the three other patients who did not report a significant sustained reduction overall pain, one had a large sciatic nerve neuroma  which waAnother patient was found to have a bony spur adjacent to the neuroma at the time of the ultrasound-guided RFA which could have contributed to her pain, whilst the third patient reported an initial reduction in pain for 1-week post RFA but then experienced a return of the pain including heightened phantom sensation. Interestingly, the third patient did not receive a routine diagnostic steroid injection prior to undertaking the RFA as we had confidently, but erroneously, assumed that the large neuroma was the cause of her pain. Apart from failure to relieve the pain in three of the patients, no complications of RFA were reported in all nine patients and no pathological changes were observed at the distal end of the targeted nerve during and after RFA.Routine regular follow up was carried out up the three-month mark post-RFA, after which the patients were given the option to return to the clinic through a self-referral (via an open appointment) or re-referral via their general practitioner/family physician if there were any further problems with pain or discomfort. At the time of writing, none of the six successfully treated patients chose to return to clinic and thus we have not observed any reports of recurrence in the longer term.Statistical analysis was performed using MATLAB . The mean pain score and standard deviation at the different time intervals (pre- and post-treatment) for all nine patients and for the six successfully treated patients were calculated. This data is tabulated in p-values for all nine patients were lower than the p-values for the six successfully treated patients. This could be explained by two factors. Firstly, Patient 1 reported an initial complete resolution of her pain (from 10 to 0 on the NRS) followed by a full return of her pain two weeks later. This outlier may have unduly influenced the p-value calculations. Secondly, reducing the already small sample size from nine patients to an even smaller sample of six patients could also have increased the p-values.Wilcoxon signed-rank test calculated the p-values of the changes in pain scores at initial presentation and the different time intervals pre- and post-treatment  for all nine patients and for the six successfully treated patients . The p-v9 In order to maintain the congruity of the axon, Schwann cells stimulate new growth of adjacent axons. However, in cases where the defect of the axon is too long to overcome by the aforementioned mechanism, the proximal axons will growth in multiple directions to overcome the defect, giving a bulbous appearance to the neuroma that is visualised on MRI and ultrasound imaging.9Neuroma formation is common after limb amputation. The type commonly found post-amputation are terminal neuromas which can occur when the proximal nerve terminal is severed during the surgery, after which apoptosis occurs in the distal axons of the nerve.10Residual limb neuroma-associated pain can be difficult to treat. A multidisciplinary approach is often required in terms of adjustments to the liner and socket by the prosthetists, psychological input, gait retraining by physiotherapy, oral analgesic changes, specialist input by the pain team and ultimately surgical excision with its associated operative risks and risk of recurrence.12 There has been one previous case series carried out by Zhang et al of 13 patients exploring the use of alcohol neurolysis in combination with RFA in residual limb neuroma associated pain.13 The authors found that in patients whose neuroma pain was resistant to alcohol neurolysis, RFA provided an effective alternative in terms of pain relief. RFA may be continuous or pulsed. Continuous RFA uses high-frequency alternating current which leads to coagulative necrosis of the neuroma. Pulsed RFA utilises the current in short 20 millisecond bursts with a half-second respite in between to allow for heat dissipation.14There is a paucity of studies in the literature concerning ultrasound-guided RFA in the treatment of residual limb neuroma-associated pain in individuals with limb amputation. These have mainly been isolated case reports.In these isolated case reports, pulsed RFA was performed at 42°C for 120-240 seconds each in two to three separate intervals, whereas in Zhang et al case series pulsed RFA was carried out at 80°C for 240 seconds each in two separate intervals. and the authors suggested this gave more consistent favourable results in terms of longer-term improvements in pain scores up to 6 months post-procedure.16 and a similar trend may also be apparent in residual limb neuroma associated pain in individuals with limb amputation.There is currently no consensus on the temperature and duration for RFA or whether it should be continuous or pulsed. Our study differs from the existing literature in that we have used continuous RFA at 90°C for nine minutes (540 seconds) which is in line with our local hospital practice. In addition to the higher temperature and longer duration, we have found that a single intervention of continuous RFA was sufficient in most of our patients in terms of sustained long-term pain relief without the need for multiple RFA treatments as seen Zhang et al’s study involving pulsed RFA. Continuous RFA is known to be more effective than pulsed RFA in the treatment of facet joint-related low back pain 19In the six patients who reported significant pain relief post-RFA, three of them also had pre-existing phantom pain and found that RFA also resolved their phantom pain completely. There are many theories as to where phantom pain originates including peripheral, spinal and central nervous system contributors. Our study supports the theories that there is a peripheral contribution. This is also supported by as Zhang et al who note that in clinical practice residual limb pain and phantom pain are often intertwined and can be difficult to separate. Severing of peripheral nerves during amputation can lead to hyperexcitability and spontaneous generation of action potentials from the cut nerve, which in turn can cause phantom pain. This theory could explain the growing use of peripheral nerve blocks to treat phantom limb pain.22 But again, like with RFA and residual limb neuromas, the number of studies and the number of patients treated could be too small to infer any concrete consensus.Undergoing a diagnostic steroid injection prior to the RFA may be a confounding factor in terms of the patient’s pain relief. US-guided steroid injections have been used to treat painful residual limb neuroma with promising early results in a few isolated case reports and a small case series.As mentioned, of the three other patients who did not report a significant reduction in pain, one had a large sciatic nerve neuroma that was eventually successfully treated with surgical excision, one had confounding pain from an adjacent bony spur  that wasThis sciatic nerve neuroma (30 x 30 mm) was almost double the size of the second-largest neuroma in our study. This might suggest that RFA would be better suited to treating pain originating from small to medium size neuromas.23 During surgical excision of a neuroma, TMR involves identifying using a nerve stimulator nearby sensory and motor nerves innervating surrounding muscle and suturing the nerves to a surgically divided distal nerve . This nerve transfer technique aims to facilitate reinnervation as close as possible to resembling physiological innervation thus potentially inhibiting the pathological central reorganisation of neuropathic pain mechanisms.24 The authors found that TMR provided greater pain relief for both residual limb pain and phantom pain on the NRS compared with traditional surgical excision of the neuroma.23 The same research group also conducted a multicentre cohort study comparing 51 patients undergoing major limb amputation with immediate TMR with 438 unselected standard major limb amputation patients. The authors found that immediate TMR at amputation reduced both phantom and residual limb pain on the NRS and may also reduce the formation of neuromas in the first place.24For larger neuromas, surgical intervention may be an inevitability. Dumanian et al carried out a randomised controlled trial of 28 individuals with limb amputation with painful residual limb neuroma assigned to either traditional surgical excision or Target Muscle Reinnervation (TMR).25 It is for these reasons that less invasive surgical excision techniques have been explored. Thomas et al conducted a case series of 10 patients with limb amputation who underwent ultrasound-guided needle localisation of their painful neuroma prior to surgical excision. The authors found that pre-operative US-guided localisation of the neuroma facilitate less invasive surgical dissections and thus potentially a reduction in the aforementioned complications.25Traditional surgical excision has also been criticised in terms of the invasiveness of the dissection. A large and invasive dissection can lead to delayed wound healing as well as excessive adhesions and scar tissue formation, which can cause pain and discomfort during prosthesis fitting. This, in turn, can lead to delays in weight-bearing and rehabilitation, A large and invasive dissection of the neuroma can also be associated with higher recurrence rates.Limitations to our study include the relatively small sample size and lack of a control group, and thus prospective cohort studies with a larger sample size may be needed to confirm our results before it can be generalised to the larger population of individuals with limb amputation with residual limb neuroma.Our retrospective case series suggests that US-guided continuous RFA is a safe and effective treatment for residual limb neuroma associated pain and phantom pain in individuals with limb amputation. US-guided RFA can reduce pain and analgesic requirements, improve comfort and ease of wearing the prosthesis and reduce the potential need for surgical excision of the neuroma and its associated surgical risks.We recommend all patients undergo a diagnostic steroid injection prior to RFA to confirm that the residual limb neuroma is the source of the pain.Further studies are needed to study the co-factors that could determine the residual limb pain and could affect the RFA treatment. This could facilitate a pre-selection of the responders to the treatment. We plan on conducting a prospective longitudinal series study with a larger sample size to investigate further the effect of RFA treatment of neuroma-associated residual limb and phantom pain in individuals with limb amputation including comparing different temperatures, durations, continuous versus pulsed RFA, as well as exploring combined RFA and phenol / alcohol injections (neurolysis).The authors declare no conflict of interest.The authors received no financial or other sources of support for this study.Dr Henderson Slater and Dr Mansour initially thought of the study. All three authors devised the study design. Dr Mansour devised the local protocol for RFA practice, collected pain scores up to 2 weeks post-treatment and the sonographic images. Dr Guo retrieved the clinical data from the patient notes, analysed and interpreted the data, and performed the statistical analysis. Dr Guo wrote and revised the manuscript with advice from Dr Henderson Slater.


Although thoracoscopic sympathectomy is made via small incisions, it is associated with severe postoperative pain. Both Rhomboid intercostal block (RIB) and serratus anterior plane block (SABP) are recent techniques used for pain control after such procedures. Herein, we compared RIB and SAPB regarding pain control in patients undergoing thoracoscopic sympathectomy for palmar hyperhidrosis.Three groups were enrolled in this prospective randomized study (71 patients in each group); Group S received SAPB, Group R received RIB and Group C as controls. The block procedures were performed after general anesthesia and prior to the skin incision.P ˃ 0.05). Pain scores showed a significant decline with the two block procedures compared to controls during the first day following surgery (both P ˂ 0.05), but Group R had better scores compared to Group S. Both block techniques were associated with a significant prolongation of the time to first rescue analgesic and less fentanyl consumption compared to controls (both P ˂ 0.05). However, both parameters were improved with RIB rather than SAPB (both P ˂ 0.05). Both blocks led to a significant improvement in patient satisfaction than in the control group (both P ˂ 0.05), but it was comparable between the two approaches (P ˃ 0.05).The three groups showed comparable demographics and operative time (Both RIB and SAPB are safe and effective in pain reduction after thoracoscopic sympathectomy procedures in patients with hyperhidrosis. Moreover, RIB is superior to SAPB as it is associated with better analgesic outcomes.https://pactr.samrc.ac.za/Researcher/TrialRegister.aspx?TrialID=21522Pan African Trial Registry PACTR202203766891354.  Primary palmar hyperhidrosis is a disorder characterized by chronic excessive sweating despite the absence of sweating triggers. With the evolution of surgical approaches, upper thoracic dorsal sympathectomy performed via video-assisted thoracoscopic surgery (VATS) is the main management option for that clinical entity .Although VATS is performed through small incisions, postoperative pain remains challenging, as some patients report sharp chest pain with deep inspiration, while others report constant pain in the dorsal region. This might necessitate prescribing opioid analgesia for proper pain relief .Postoperative pain not only increases patients' anxiety but also decreases postoperative satisfaction and hinders early rehabilitation, so effectively preventive post-operative pain is important . DiffereDisadvantages of the previously mentioned techniques are infection, hematoma parasympathetic manifestations, paraspinal muscular pain, spinal anesthesia, and short duration of analgesia , 7.Recently, rhomboid intercostal block (RIB) and serratus anterior plane block (SAPB) have been described to provide effective analgesia after thoracic procedures , 9. RIB This prospective randomized controlled parallel study was conducted over one year, starting from March 2022 to March 2023, at Mansoura university hospitals after the Institutional Research Board and ethical committee of our university (MFM-IRB) approval R.21.09.1462) on 31/10/ 2021. The study was designed for 213 patients with severe palmar hyperhidrosis after explaining its benefits and potential risks. Patients were interviewed, and written informed consent was obtained. All methods were performed in accordance with the declaration of Helsinki. The study was registered in the Pan African Trial Registry (PACTR202203766891354) on 16/3/2022. The study was reported according to the Consolidated Standards for Reporting Trials (CONSORT) guidelines) pain score 6 5–7 –10) vs.  vs. 10])ontrols) .P < 0.01). The amount of rescue analgesia also decreased significantly in the SAPB group (P = 0.02) during 0–12 h [Moreover, Chen and his associates evaluated the effects of SAPB on postoperative pain after thoracoscopic surgery compared with local anesthetic (LA) infiltration. Postoperative sufentanil consumption in the SAPB group was significantly lower compared with the LA group (g 0–12 h .There are limitations of our study as the patients were collected from a single medical center, both block techniques were performed as a single shot, and its effect on chronic postoperative pain was not evaluated. That is why we recommend performing more studies with a larger patient sample.Both RIB and SAPB are safe and effective in pain management after VATS procedures for hyperhidrosis. However, RIB is superior to SAPB as it is associated with better analgesic outcomes.


We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment.Eighty patients were enrolled. Patients in group S received ondansetron 4 mg in saline in the right hand followed 30 min later by 5 mL saline in the left hand along with venous occlusion. Group L patients received 4 mL of saline in the right hand followed by 5 mL 4 mg ondansetron in the left hand after 30 min. Two minutes later the occlusion was released. Patients received one-fourth of the calculated total dose of propofol, and their level of pain was graded on a scale of 0 to 3, with 0 denoting no discomfort. Mean blood pressure and heart rates were also recorded. Continuous variables were checked for normality using Shapiro-Wilks test. Normal continuous variables were expressed as mean standard deviation and non-normal continuous variables were expressed as median interquartile range. T-test for the difference in the mean and paired test were used for normally distributed continuous variable whereas Mann-Whitney U test-Wilcoxon test and sign test were used for non-normally distributed variables. Repeated measure analysis of variance was used for a variable measured over different periods of time to control for the baseline effect on subsequent measures.Our results demonstrated that both systemic administration 30 min before and local venous pretreatment with ondansetron were equally beneficial in reducing pain during propofol injection.A systemic administration of ondansetron may play a role in the attenuation of propofol injection pain. According to several of these patients, the most unpleasant phase of the perioperative period was anaesthesia’s induction. To alleviate this pain from propofol injection, many therapies have been researched. According to a 2000 comprehensive review, the most efficient technique was venous occlusion followed by lidocaine pretreatment.2 However, due to the time required to apply the tourniquet, this approach is not very popular. The discomfort brought on by the injection of propofol continues to be a matter of concern and more than 100 new researches have looked into additional and alternative methods. These include novel propofol emulsions,4 modified emulsions, and microemulsion formulations,7 part from other drugs and interventions.Given its rapid onset and short duration of action, ease of titration, and benign side effect profile, propofol 2,6-di-isopropyl phenol is an extremely popular medication for inducing anaesthesia worldwide.8 Ondansetron is a useful alternative for the alleviation of propofol injection pain.10The 5-hydroxytryptamine (5-HT) antagonist ondansetron blocks sodium channels in rat brain neurons and is 15 times more potent than lidocaine on subcutaneous injection.11 However, there are conflicting reports about this role of ondansetron. The local anaesthetic lidocaine has been found to alleviate the pain of propofol injection by both local anaesthetic and central analgesic effects.12 We designed our study to determine if systemic ondansetron was also effective in attenuating pain on propofol injection similar to ondansetron pretreatment. Our hypothesis was based on the premise that propofol injection pain is systemically induced, as suggested by Nakane and Iwama.13Intravenous ondansetron has also been found to be an effective treatment for neuropathic pain.This double-blind randomized controlled trial was conducted after obtaining ethical approval from the Institute Ethics Committee, Indira Gandhi Institute of Medical Sciences: Sheikhpura: Patna-14 Office of the . The trial was registered prospectively with the national trial registry. Before enrolment, written informed consent was obtained from all patients. This manuscript adhere to the applicable CONSORT guidelines. The study was conducted at a university hospital between February 2020 and March 2021 and is in accordance with the tenets of the Helsinki Declaration (as amended in 2013).We included 80 patients aged 18-60 years of either gender and American Society of Anesthesiologists (ASA) class I to II scheduled for elective surgery. Exclusion criteria included patient sensitivity to ondansetron and those on concomitant analgesics, sedatives, or antiepileptic medications. Patients were randomly allocated into two groups with 40 patients in each group using a computer-generated randomization list. Sequentially numbered, opaque sealed envelopes were used to conceal the randomization sequence. The investigator and the patient were unaware of the group allocation. An independent clinician prepared the study medication.The previous evening, all patients were orally provided alprazolam 0.5 mg and ranitidine 150 mg. On the day of surgery, no premedication was administered. A 20-gauge intravenous cannula was placed in the dorsum of both hands as soon as the patient entered the operating room, following the application of ECG, non-invasive blood pressure, and pulse oximeter monitoring. No analgesics were administered before induction. On the left upper arm, a pneumatic tourniquet was applied, and the pressure was raised to 70 mmHg to cause venous occlusion.14 while a pneumatic tourniquet (pressure raised to 70 mmHg) was applied to the upper arm to occlude venous drainage. The occlusion was released after 2 min. Thereafter, one fourth of the total calculated dose of propofol  stored at room temperature was administered for a period of 5 s and patients were assessed by an independent clinician for pain intensity. We questioned each patient if they found the injection to be comfortable. The verbal response was observed along with behavioral cues such as tears, facial grimacing, or arm withdrawal.15 The pain was graded on a scale of 0 to 3, with 0 indicating no pain, mild pain, moderate pain, and severe pain, respectively. Mean blood pressure (MAP) and heart rate (HR) were recorded immediately before the interventions and before and after propofol administration. Rescue medications in the form of atropine for bradycardia less than 50 bpm and mephenteramine for hypotension less than 20% of the baseline value were administered. After giving fentanyl, the remaining amount of propofol was used to continue the anaesthetic induction. Vecuronium was used to assist tracheal intubation, while isoflurane, nitrous oxide in oxygen, and intermittent positive pressure breathing was used to maintain anaesthesia.Patients in group S received ondansetron 4 mg (2 mL)  in saline (2 mL) intravenously over 10 s in the right hand. They were given 5 mL of the pretreatment solution  intravenously 30 min later over the course of 10 s, while the venous drainage was restricted by applying a pneumatic tourniquet to the upper arm at a pressure of 70 mmHg. The occlusion was released after 2 min. Group L patients received 4 mL saline intravenously over 10 s in the right hand. After thirty minutes, patients received a 5 mL pretreatment solution  intravenously in the left hand over a period of 10 s,15 Another study showed a 25% incidence of pain among patients who received ondansetron 4 mg in 2 mL saline intravenously over 10 s.9The primary objective of this study was to determine the incidence and severity of pain on propofol injection following local or systemic administration of ondansetron. In one study, the incidence of propofol pain was 46% when patients were administered 4 mL of saline intravenously over 10 s.Based on these informations, the sample size, at 5% level of significance and 80% power to detect the difference in incidence rate between the two groups, was approximately 80, i.e., 40 in each group.P<0.05. Normally distributed variables were given as mean, standard deviation, and non-normal distributed variables were expressed as median and interquartile range. Independent samples t-test was used for normally distributed data comparing two groups, whereas the Mann-Whitney U test was used for non-normally distributed variables. Paired sample t-test was used, and Wilcoxon signed-ranked tests were used to compare dependent samples. Repeated measure analysis of variance was used for variables measured over different periods.Analyses were performed using Stata version 10  and IBM SPSS 22.0 . Continuous variables were checked for normality assumptions using Shapiro-Wilks test. The statistical significance level was determined as Mauchly’s test of sphericity was used for checking the sphericity assumptions. In the case of significant violation of the sphericity assumption, Greenhouse-Geisser corrections were applied for adjusting the degree of freedom. Post-hoc comparisons between different pairs of time were done after Bonferroni corrections.P=0.793).A total of 80 patients were included in the study and there was no dropouts . Table 1P=0.0001). Hence Greenhouse-Geisser corrections were applied for adjusting the degree of freedom. The mean HR was significantly different across the three time points . A post-hoc pairwise comparison using the Bonferroni correction showed a minimum change in HR between the baseline assessment and before pre-treatment assessment (mean difference =-0.138), but this was not statistically significant (P=1.00). However, a decrease in HR reached significance when comparing the initial assessment to post-treatment assessment  and also between pre- and post-treatment assessments , respectively. Therefore, we can conclude that the results of ANOVA indicate a significant difference in HR between the two groups at various time intervals.A repeated measures ANOVA was applied to test the equality of mean HR across three time points, as shown in P=0.0001). Hence Greenhouse-Geisser corrections were applied for adjusting the degree of freedom. The mean MAP was significantly different across the three time points . A post-hoc pairwise comparison using the Bonferroni correction showed a minimum change of MAP between the baseline assessment and before pre-treatment assessment (mean difference =-0.438), but this was not statistically significant (P=0.706). However, a decrease in MAP reached significance when comparing the initial assessment to post-treatment assessment  and also between pre- and post-treatment assessment , respectively. Therefore, we can conclude that the results of ANOVA indicate a significant difference in MAP between the two groups at various time intervals.Repeated-measures ANOVA was applied to test the equality of mean MAP across three time points, as shown in Our results suggest that both systemic administration and local venous pretreatment with ondansetron were equally effective in alleviating pain on propofol injection.9 A single intravenous dose of ondansetron was found to act as an analgesic for neuropathic pain, suggesting its systemic action.11 We planned our study to find out if systemic ondansetron was also effective in alleviating propofol injection pain similar to local ondansetron pretreatment.Intravenous pretreatment with ondansetron has been successful in attenuating pain on the injection of propofol.14Ondansetron is routinely used at our centre for the prevention of postoperative nausea and vomiting, usually in a dose of 4 mg. Based on an animal experiment, it was felt that 30 min was appropriate for ondansetron to reach the cerebrospinal fluid and exert its systemic action.P=0.793).In our study, 42.5% of the patients who received systemic ondansetron reported no pain on injection compared with 50% of those administered local pretreatment. Also, the incidence of moderate pain (20% versus 12.5%) and severe pain (7.5% versus 5%) was higher in the patients who were administered systemic ondansetron compared with the local ondansetron pretreatment group. However, none of these were statistically significant , ankyrin 1, and TRP vanilloid 1 have been found to mediate release of neuropeptides and produce propofol-induced pain.18Skin, mucous membrane, and venous intima get irritated by propofol, which is chemically phenol. A high aqueous free propofol concentration has been implicated in causing injection pain.19We used a propofol formulation containing medium chain triglyceride because it has a reduced concentration of free propofol in the aqueous phase and is known to cause lesser pain on injection.21 Serotonin plays a crucial role in the endogenous analgesia process. Serotonergic neural regulation that descends to the spinal cord from the rostral ventromedial medulla reduces neuronal activity and hypersensitivity and aids in analgesia.22 This has been linked to the serotonin activity on the G-protein coupled 5HT-1 and 5HT-7 subtypes of serotonin receptors.23 G-protein coupled receptors also play some role in the attenuation of propofol-induced pain.9 However, there are certain limitations to our study. Due to ethical concerns, a placebo group was not included in our study. Estimation of cerebrospinal fluid and serum levels of ondansetron could not be performed for logistic reasons.In animal models of nerve damage, it has been hypothesized that intrathecal injection of 5HT-3 receptor antagonists such as ondansetron reduces mechanical and thermal hypersensitivity.The findings that systemic administration of ondansetron may play a role in alleviating propofol injection pain can be a basis for further research into its use as an analgesic in pain models other than neuropathic.


Objectives® (CK) radiosurgery; secondary endpoints were to assess early side effects and complications.Stereotactic radiosurgery combined with pharmacological treatment is currently one of the most acceptable alternatives for the treatment of trigeminal neuralgia (TN). Our primary endpoint was to report the short-term response (one month) outcomes of 10 patients with refractory TN after CyberKnifeMethods® radiosurgery. Clinical and demographic characteristics were obtained from medical records. The visual analog scale (VAS) was used to assess facial pain before as well as seven, 15, and 30 days after treatment. Friedman test was performed to evaluate pain relief in treated patients.Ten female patients with TN refractory to pharmacological and/or non-pharmacological treatment received a single dose of 90 Gy with CyberKnifeResultsAll patients responded well to the CK and experienced initial adequate pain relief during the first 30 days (p<0.001). No significant differences (p=0.661) were found between six patients who received CK radiosurgery as the first treatment option and those who underwent other non-pharmacological treatments. One patient was re-irradiated with 75 Gy. Transient facial paresthesia was observed in 3/10 patients without any other complications.ConclusionHigh-tech CK treatment is safe, non-invasive, fast, with minimal side effects, and effective in achieving short-term pain relief in patients with refractory TN, even in those with multiple previous interventions. Given these results, we recommend evaluating CK radiosurgery as the first-line treatment of choice for trigeminal neuralgia refractory to pharmacological treatment. Trigeminal neuralgia (TN) is defined as a sudden, brief, and excruciating facial pain in one or more of the branches of the trigeminal nerve , leading to a severe reduction in the quality of life . This crThe classical theory of the pathophysiology of TN is microvascular compression, which is due to the vascular contact usually of the superior cerebellar artery; this compression results in demyelination of the nerve fibers of the trigeminal nerve .Pharmacological therapy with one or more drugs is considered the appropriate initial treatment . The antStereotactic radiosurgery combined with pharmacological treatment is currently one of the most acceptable alternatives for the treatment of TN , howeverOur primary endpoint was to report the short-term response (one month) outcomes of 10 patients with refractory TN after CyberKnife® (CK) radiosurgery. Secondary endpoints were to assess early side effects and complications.Patient selectionPatients with refractory trigeminal neuralgia who underwent CyberKnife® radiosurgery between September 2022 and March 2023 at Oncoserv, Santo Domingo in the Dominican Republic participated in this study. These patients were refractory to pharmacological treatment, that is, those patients with at least six months of pharmacological management at optimal doses and who did not show a favorable response. We also selected patients who had undergone other treatments such as peripheral nerve block or decompressive microvascular surgery without favorable response, and those patients who, due to other comorbidities and age, were poor candidates for decompressive microvascular surgery and those who did not show clear evidence of such compression according to imaging studies.The medication administered to the patients was carbamazepine alone or combined with other drugs: pregabalin+B complex in five patients, duloxetine in two patients, gabapentin in one patient, and oxycodone in one patient.Sex, age at the time of the procedure, previous non-pharmacological treatment, region of pain, side and cranial nerve branch affected(s), and also time since diagnosis of pain were obtained from medical records. The visual analog scale (VAS), a validated and subjective measure for acute and chronic pain which values between 0 (no pain) to 10 (worst pain) , was useRadiosurgical procedure - treatment planningThe treatment point was located 4-5 mm from the apparent origin of the trigeminal nerve or dorsal root entrance zone (DREZ). The prescribed dose was 76.5 Gy at 85% at a planning target volume (PTV) of 5 mm, to achieve a dose point of 90 Gy Figure , with thThe system used was CyberKnife® G4 radiosurgery system, which consists of a 6MV X-band linear accelerator mounted on a robotic arm that is fully articulated and has an accuracy of 0.3 mm with six degrees of freedom.Prior to treatment, planning for each intervention included high-resolution simulation CT (1 mm slice thickness), fast imaging employing steady-state acquisition (FIESTA), 1.5 Tesla resonator MRI in T1 and T2 with and without contrast. Patients were immobilized with a standard cranial mask at CyberKnife®. Treatment planning was then performed in MultiPlan software with CT and 3D. CyberKnife® treatments were developed using the 5 mm diameter cone.Statistical analysesThe Friedman non-parametric repeated measured analysis  was perfTable All patients had 10/10 pre-treatment pain on the VAS scale. The first month all patients had statistically significant pain response . At seven days after treatment, the mean pain was 6 points, at 15 days it was 4 points and at 30 days it was 2 points.Table Figure Before treatment all patients had a pain level of 10/10 VAS; in the first week after treatment, they had an immediate response and went on to have a median level of 6/10. Immediate and successful pain relief has been reported at a median time of seven days ,16. SeveRomanelli et al. were the first clinical demonstration of the accuracy, safety, and efficacy of Cyberknife radiosurgery in the early relief of TN pain ; in thisAdler et al.  indicateAt 15 days, the median level was 4/10 and at 30 days this value was reduced to 2/10. One month later, two of the treated patients reported no pain at all, while the others reported the following degrees of pain: 1/10 (one patient), 2/10 (three patients), 4/10 (three patients), 5/10 (one patient). It is important to highlight that in our case of re-irradiation, the improvement of pain was 4 points at seven and 14 days (6/6 VAS), reaching a value of 5/10 VAS at 30 days.Berti et al.  indicateFor Gamma Knife® (GK) surgery pain relief usually begins a mean of three weeks after radiosurgery, and could continue to improve up to six months .All treated patients were women, which coincides with some studies that report a higher incidence in women -26 but oTransient facial paresthesia with resolution in less than 24 hours was present in three patients, without other acute complications. This is consistent with Lakshman et al.  who indiAntiepileptic drugs such as carbamazepine, neurontin, and phenytoin are the first line of treatment for TN . During In 60% of our patients, CK radiosurgery was the non-pharmacological treatment of the first choice, providing patients with satisfactory symptom relief. In our experience, even patients who received previous non-pharmacological treatments , had a favorable short-term response with CyberKnife radiosurgery.In this simple retrospective study, we can appreciate the usefulness of radiosurgery in the treatment of trigeminal neuralgia. CK is a tool that offers promising results with low toxicity. Patient selection is critical to obtain favorable results.Pain relief is essential to provide quality of life for these patients, and that objective is met in this work. The results of this study coincide with those published in the literature and increasingly support this indication for treatment.As a limitation of this research, we highlight the scarce availability of articles on short-term pain response (during the first month) in refractory trigeminal neuralgia treated with Cyberknife radiosurgery. We are evaluating the short-term results (one month) of treatment with CK, there are no articles focused as such to measure this, therefore this can serve as support for other research, however, we recognize that there is a need for studies that evaluate short-term response in larger groups with longer follow-up, we highlight that the evidence presented is clinically and statistically significant in the short term in our cases presented.High-tech CK treatment is safe, non-invasive, fast, with minimal side effects, and effective in achieving short-term pain relief in patients with refractory TN, even in those with multiple previous interventions. Given these results, we recommend evaluating CK radiosurgery as the first-line treatment of choice for trigeminal neuralgia refractory to pharmacological treatment. We are considering the need for a comparative study with a larger number of patients and a longer follow-up period.


Chronic pain of various origin is known to be associated with selective cognitive impairment. Osteoarthritis (OA) of the hip is one of the leading causes of chronic pain in the adult population, but its association with cognitive performance has not been evaluated. Here, we investigate the effect of chronic pain due to unilateral OA of one hip and no further source of chronic pain on cognitive performance.A neuropsychological test battery, consisting of the Mini-Mental State Examination, Rey–Osterrieth complex figure test, Rivermead behavioural memory test, d2 test of attention, and F-A-S test was applied in 148 patients and 82 healthy pain-free control individuals. The influence of potentially confounding factors such as depression and anxiety was examined.Patients with OA of the hip showed decreased performance in specific neuropsychological tests. Performance in verbal and visual short-term and long-term memory and selective attention tests was significantly poorer compared to healthy controls. Whereas the executive functions “updating”, “set shifting”, “response inhibition” and “reflection” appear intact, “problem solving” and “planning” were impaired. None of the confounders showed any influence on cognitive performance in both study groups.We conclude that chronic pain secondary to end-stage hip OA is associated with selective cognitive impairment. Future studies are required to investigate the effect of total hip arthroplasty on cognitive performance.The online version contains supplementary material available at 10.1007/s00402-022-04445-x. Chronic pain represents a crucial factor of direct, indirect, and intangible costs to society, economy, and affected patients with a reported prevalence of 19% in the European population  first deTo the best of our knowledge, there are no studies examining all cognitive functional areas and considering potential confounders for a specific cause of chronic pain. Prakash et al.  showed tRegarding OA of the hip, we have previously demonstrated that gray matter is reduced in patients with chronic pain in the anterior cingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, island, and operculum , 17. IntAlthough the prevalence of hip OA is > 7% within the age group of 60–90 years , and thuSince depression is associated with cognitive impairment , and theThe primary objective of the present study was to investigate the cognitive performance in chronic pain patients due to unilateral hip OA in comparison to a healthy CG. The secondary goal was to evaluate the effect of depression and anxiety on the relationship between pain and cognition.This study was performed as a single institution prospective clinical trial. The inclusion criterion for the chronic pain group (CPG) was chronic pain caused by end-stage unilateral hip OA, scheduled for elective total hip replacement surgery. Based on patient´s symptoms, orthopedic examination, and radiograph images the diagnosis of end-stage OA was confirmed. The severity of the OA was described by the Kellgren–Lawrence grade. Exclusion criteria were chronic pain of further origin, bilateral hip osteoarthritis, dementia, substance-related addiction , current psychiatric treatment, untreated visual or hearing impairment or lack of German language skills. The same criteria were applied to the healthy CG, with the only difference being chronic pain of any origin as an exclusion criterion. The CG consisted of healthy volunteers recruited by word-of-mouth, e-mail announcements, flyers placed in general practitioners' offices and through invitations to residents of senior citizen housing facilities. All study participants were informed about data protection regulations before the start of the study. Prior to study participation, written declaration of consent of all participants was signed and archived. The study conforms to the principles of the Declaration of Helsinki, was approved by the local research ethics committee (PV5016) and registered with ClinicalTrials.gov (NCT02997891).Demographic and clinical data including age, gender, employment, comorbidities, pain medication and pain intensity in the last 7 days using the visual analog scale (VAS) were collected. Hip function was recorded by the Harris Hip Score (HHS) only in the CPG.The Mini-Mental State Examination (MMSE) was performed to detect dementia and exclude patients and controls with a score of 24 and below. The distinct cognitive dimensions were investigated by the following neuropsychological tests:The participant is requested to draw a complex figure with a total of 18 items, afterwards the figure must be drawn from memory and after another 30 min again. The ROCFT measures the visual construction and the visual memory performance.The RBMT is a diagnostic test consisting of eleven tasks to identify memory problems. We used the sub-test “story” to examine verbal short- and long-term memory. A short story is read aloud, and the test person is asked to give a verbatim report of it . After 30 min, the participant is asked to repeat the story again . Each reproduced item was awarded with points for verbatim or analogous items reproduction. Conclusions about the executive functions “problem solving” and “planning” were drawn of the results.d" in 14 lines with two marks around above or below it in any order. The patient has 20 s per line to mark all items between wrong items. From the correct, incorrect, and omitted markings, scores can be formed, of which the “concentration performance” (CONC) is derived. CONC describes the number of correctly detected target items minus the number of errors of commission. The test is suitable for the examination of selective attention. Furthermore, the evaluation of “wrong marking errors” allows conclusions about the executive function "response inhibition".The participant must mark any letter "The TMT part A comprises numbers from 1 to 25, which must be connected in ascending order as quickly as possible. In part B, letters are mixed in between, and the participant must alternately combine numbers and letters in sequence (1–A–2–B–3–C… 13–J). The time required for the two parts represents a measure of attention and executive function "updating" and "set shifting". Psychomotor speed and visual perception exert a significant influence. By subtracting A from B, the influence of psychomotor speed can be reduced .The task of the F-A-S test is to enumerate as many words as possible with the initial letter "s" in 60 s. Personal names and words with the same word stem are not validated. The total number of words was not only used for the short-term memory, but also for the evaluation of the executive function . “Set shThe potentially confounding factors depression and anxiety were determined by means of questionnaires. The Patients Health Questionnaire (PHQ-9)  and Genet-tests for continuous data to determine whether significant differences exist between CPG and CG. To analyze whether these differences are also clinically relevant effect sizes according to Cohen  were calculated for each t-test [r). Since age has a possible influence on neuropsychological test results partial correlations  were calculated to exclude the influence of this variable if necessary. Additionally, descriptive statistics were calculated to present demographic data by means, standard deviations, and percentages. Any differences in sociodemographic parameters were analyzed by t-tests for continuous data and Chi-square tests for categorical data. Data analyses were performed with SPSS statistical software version 25  and JASP (Version 0.14) [P values ≤ 0.05 were considered statistically significant.The primary outcome, differences in cognitive performance, was evaluated using independent h t-test . The effon 0.14) . P valuep < 0.001) in pain between CPG (mean 6.1 ± 2.1) and CG (0.9 ± 1.3). No neurological comorbidities, such as brain trauma, stroke or epilepsy were reported. A synopsis of means and standard deviates of the neuropsychological test results are presented in supplementary Table 1.The study enrolled 148 patients with unilateral OA of the hip into the CPG out of a total of 575 respondents who were screened for participation. In the CG, 83 participants out of a total 114 respondents were included. One participant of the CG had to be excluded from the study due to a MMSE result < 25. Demographic and clinical data, including outcomes of depression and anxiety scores, are listed in Table p < 0.001, d = 0.62; “ROCFTmemory quotient” p = 0.001, d = 0.51; “RBMTrecall” p < 0.001, d = 0.80; “RBMTdelayed recall” p < 0.001, d = 1.15; . The investigation of split attention (TMTB) bordered on significance . According to the results of TMTB and the.Wrong markings from the d2 test were used as a measurement value for the executive function "response inhibition". There was no evidence for a significant deterioration of “response inhibition” in the CPG , “set shifting", "updating" and “complex executive functions” did not indicate significant differences between the groups  between r = 0.225 and r = 0.446 were found between age and all but one neuropsychological test parameter. The sum of errors of the d2 test showed no significant correlation with age (p = 0.691). Taken the effect of age into account, partial correlations between VAS pain intensity and neuropsychological test parameters demonstrated significant correlations for selective attention , visual memory  and verbal memory  but not for psychomotor speed .Significant small to moderate correlations  and the impact of potential confounding factors (depression and anxiety) on cognitive performance in 148 patients with chronic pain due to end-stage unilateral hip OA. We compared the results to a CG of 82 free of chronic pain of any cause. The major finding is that chronic pain due to hip OA is associated with significantly worse test results with high effect sizes in neuropsychological tests measuring verbal/visual short-term, long-term memory and selective attention. Executive functions are only partially impaired, with lower scores for “problem solving” and “planning”, while “updating”, “set shifting”, “response inhibition”, and “reflection” appeared intact. In a follow up study of this patient collective, Strahl et al.  demonstrmemory and attention (measured by ROCFT and RBMT), the present findings do correspond to previously published results on cognitive impairment in patients with chronic pain of other etiology [Regarding etiology , 36–40.executive function, the effect of chronic pain is more diverse. Executive functions are a set of cognitive processes that are necessary for cognitive control of behavior. Some executive functions are clearly impaired in hip OA such as “planning” and “problem solving” (measured by ROCFT), while others do not seem to be altered in patients with chronic hip OA pain. For example, “response inhibition” (measured by wrong markings in the d2 test), “reflecting” (measured by F-A-S), “set shifting” and “updating” (measured by TMTB and TMTB–A) did not show any difference.Regarding Interestingly, some of these qualities, which are not affected by chronic hip OA, have been previously described to be altered in patients with other chronic pain conditions. Specifically, “set shifting” was shown to be impaired in patients with fibromyalgia , 41 and Other qualities such as “planning” and “problem solving” have previously been shown to remain unaffected in patients with rheumatoid arthritis compared to a healthy CG .Taken together, the present results and previously published work demonstrate that cognitive functions are subject to change in patients with chronic musculoskeletal pain in a complex, not a uniform, manner. The extent of cognitive impairment appears to depend on the cause of chronic musculoskeletal pain, pain intensity, pain progress and pain localization. Further delineating specific interactions of the various qualities of the CNS cognitive function with various chronic OA pain qualities from, e.g., knee, hip, and shoulder, may help counseling patients regarding the options and expected benefits of elective joint replacement surgery beyond pain control.In the present study, there was no significant influence of depression or anxiety on cognition Table . This isIncreasing pain severity has been demonstrated to be associated with decreased cognitive performance in patients with chronic back pain, visceral, musculoskeletal, and neuropathic pain , 50, 51.Patients were generally tested a week or two before elective total hip arthroplasty. Awaiting surgery might have an influence on performance in neuropsychological tests. However, since anxiety had no influence on the test results, we consider it rather unlikely, that the prospect of surgery played a significant role.Chronic pain due to end-stage hip OA is part of an emerging complex network of CNS interaction with the musculoskeletal system. It is associated with selective impairment of certain qualities of cognitive performance and this effect is independent of depression or anxiety. The current findings provide the rationale for future studies investigating to which extent total hip arthroplasty may improve cognition in elderly patients and, thus, provide benefits that may go well beyond pain control.Supplementary file1 (DOCX 20 kb)Below is the link to the electronic supplementary material.


In the past three decades, the use of opioids has risen tremendously. Pain was named the “fifth patient vital sign” in the 1990s, and from that point, opioid usage has continued to grow throughout the 2010s leading to its recognition as a crisis. The United States is responsible for 80% of the global opioid usage while only accounting for less than 5% of the global population. Previously opioids were mostly used to treat acute pain, however, opioids have been most recently used to manage chronic pain as well. The opioid crisis has presented new challenges in treating pain while preventing the abuse of these medications in a system that lacks standardization of treatment guidelines across the United States. Therefore, the authors of this review examine the current national recommendations to help manage the ongoing opioid crisis and explore how they may impact orthopedic patient care. Declared a national public emergency in 2017, the opioid epidemic has surpassed 100,000 annual deaths and has exhibited a 600% increase since 1999 . The risIn 2016, the Centers for Disease Control and Prevention (CDC) released the “Guideline for Prescribing Opioids for Chronic Pain,” however, each state still maintains its autonomy regarding prescribing practices . In turnOrthopedic surgeons most commonly prescribe opioid medications following injury or surgery for acute pain. In 2019, a study determined that orthopedic surgeons frequently prescribed more opioid medications than were required for patients with more extensive past surgical histories . AdditioGiven the complexities of the current issue, it is imperative that our community examines the fundamentals of opioid medications as a form of treatment and their addictive properties that affect orthopedic patients. In doing so, the authors assess the following: (1) patient perception of pain control, (2) impact of the opioid epidemic on surgeons and patients, (3) opioid abuse prevention and prescribing strategies in the face of an opioid epidemic, 4) how varying prescribing guidelines affect orthopedic patient care, and (5) effect of online prescription drug monitoring.Patient perception of pain controlThere are several significant barriers to effective pain management. These include the following: (1) inadequate knowledge of healthcare professionals, patients, and the public, (2) poor communication between patients and providers, poor communication between providers, and lack of institutional commitment, and (3) regulatory concerns, limited access, and reimbursement for interdisciplinary care . DespiteGupta et al. analyzed the data from the HCAHPS survey focusing on the level of patient satisfaction with their pain control. Their analysis demonstrated that 63% of the patients surveyed were globally satisfied with pain control which highly correlated with quality of care. Additionally, the patient's relationship with healthcare staff was highly correlated with pain relief. Interestingly, government-owned hospitals accounted for the highest pain relief and privately owned hospitals accounted for the lowest pain relief. Lastly, community-level hospitals displayed the lowest satisfaction rates, while tertiary centers had the highest. Although this study evaluated data before the height of the opioid crisis, Gupta et al. provide some insight as to how subjective pain scores may correlate with patient overall satisfaction. The same researchers subsequently analyzed the HCAHPS survey report from December 2012, which showed improved patient pain control and satisfaction, however, some discrepancies were noted between the levels of hospital care, with all hospital ownership types demonstrating improved pain control .Although largely subjective, accurately assessing a patient’s pain is essential. Typically, a numeric rating scale (NRS) utilizes an 11-point pain scale to measure pain severity (0=no pain and 10=worst possible pain). Oftentimes, the patient’s perceived pain score (PS) might not align with the clinical interpretation. In a 2021 prospective study, Bakshi et al. studied pain perception in post-operative patients. Patients were questioned to rate their PS on the NRS, followed by a briefing about the clinical interpretation of the scale. The patients were then rescored and differences in scores were analyzed. There was a statistically significant change in PS in 45% (162 patients), with 119 patients decreasing their post-explanation PS and 41 patients increasing their PS. However, there was no significant association with gender, time of examination, or pain management modality . In concThe impact of the opioid epidemic on surgeons and patientsInadequacies in treating pain in the hospital setting have been shown to lead to extended hospital stays and higher mortality . Beesdo Orthopedic surgeons often treat patients with acute injuries and chronic conditions that require surgery. Following surgery, many of the patients receive opioid medication as part of their treatment plan to provide pain relief. In the United States, orthopedic surgeons are the fourth highest prescribers of opioids, making up an estimated 7.7% of all opioid prescriptions behind only primary care physicians (28.8%), internists (14.6%), and dentists (8.0%) .A significant risk factor for post-operative opioid abuse is pre-operative opioid use. A recent study of patients who underwent total shoulder arthroplasty suggests a 3.5 times higher risk of post-operative dependence in patients who used opioids prior to their surgery with longer durations of post-operative use . While nOpioid abuse prevention and prescribing strategies in the face of an opioid epidemicThe U.S. Department of Health and Human Services seeks to improve access to treatment and recovery services by promoting opioid-reversing drugs, strengthening the understanding of the crisis, promoting research on pain and addiction, and advocating for improved pain management practices. Currently, however, each state maintains its own autonomy by implementing its own prescribing practices which makes the navigation of these differences challenging .The primary policy implemented by many states is to limit the number of opioid pills provided in an initial prescription (table in the Appendix) ,22. In 2The U.S. federal government has yet to require opioid analgesic prescribing limits, however, in recent years, it has released its guideline for prescribing opioids in chronic pain which includes 12 recommendations  are a promising tool implemented at the state level, which allow a physician to monitor all controlled substances prescribed to a patient. Twenty percent of prescription drug users receive their prescriptions from a single prescriber. In contrast, a growing number seek their prescriptions from multiple providers, known as “doctor shopping” . The tooThe literature on PDMP efficacy is mixed, with some studies showing that PDMPs are ineffective at preventing or reducing opioid-related deaths . HoweverEffective use of PDMPs can also have other positive influences on patient care. In one study, 54% of providers surveyed stated that they had made mental health or substance abuse referrals based on PDMP review, even in the setting of patients who were unlikely to ask for help when opioid abuse or dependence was demonstrated . The useOrthopedic surgeons are often tasked with treating patients with acute or chronic pain. Prescribing patterns by orthopedic surgeons have certainly contributed to the opioid crisis amid inconsistent state or federal regulation. The opioid crisis remains a difficult challenge to overcome; nevertheless, strides must be undertaken at federal and state levels to standardize practices involving opioid management, and prescribers must reflect on their prescribing habits and lead the efforts to overcome their contribution to the crisis.


Chronic pain (CP) has been found to cause significant alternations of the brain’s structure and function due to changes in pain processing and disrupted cognitive functions, including with respect to the prefrontal cortex (PFC). However, until now, no studies have used a wearable, low-cost neuroimaging tool capable of performing functional near-infrared spectroscopy (fNIRS) to explore the functional alternations of the PFC and thus automatically achieve a clinical diagnosis of CP. In this case-control study, the pain characteristics of 19 chronic pain patients and 32 healthy controls were measured using fNIRS. Functional connectivity (FC), FC in the PFC, and spontaneous brain activity of the PFC were examined in the CP patients and compared to those of healthy controls (HCs). Then, leave-one-out cross-validation and machine learning algorithms were used to automatically achieve a diagnosis corresponding to a CP patient or an HC. The current study found significantly weaker FC, notably higher small-worldness properties of FC, and increased spontaneous brain activity during resting state within the PFC. Additionally, the resting-state fNIRS measurements exhibited excellent performance in identifying the chronic pain patients via supervised machine learning, achieving F1 score of 0.8229 using only seven features. It is expected that potential FC features can be identified, which can thus serve as a neural marker for the detection of CP using machine learning algorithms. Therefore, the present study will open a new avenue for the diagnosis of chronic musculoskeletal pain by using fNIRS and machine learning techniques. Chronic pain (CP) refers to pain that persists after a normal healing period, lasting or recurring for over 3 months ,2. CP afMore importantly, recent advances in neuroimaging techniques and methods such as electroencephalography (EEG), functional magnetic resonance (fMRI), and functional near-infrared spectroscopy (fNIRS) have offered better opportunities to fully understand the cognitive neural mechanisms underlying CP during a task  or at reIn this study, we will analyze whether FC and spontaneous brain activity of the PFC are changed in CP patients compared to those of HCs. We will also examine the topological properties of the PFC, such as the clustering coefficient and path length, by using graph theoretical network analysis . It is eIn this study, 52 right-handed participants, including 19 chronic musculoskeletal pain patients  and 32 age- and gender-matched HCs , were recruited from the First Affiliated Hospital of Sun Yat-sen University. All patients, who were afflicted with pain that had lasted over 6 months and free of any neurologic or metabolism diseases, were diagnosed with chronic musculoskeletal pain by three physicians. All participants provided informed consent prior to the experiment. The present study protocol was approved by the Institutional Review Board at both the University of Macau and Sun Yat-sen University.All participants underwent a 5 min session of resting-state fNIRS recordings. They were seated in a comfortable chair and instructed to keep still and not to think about anything purposely. It was observed that none of the participants slept during the fNIRS data recording. Our experiment was conducted by utilizing a fNIRS system  transmitting at two wavelengths, namely, 760 and 850 nm, to measure HbO and HbR concentration changes with 50 HZ sampling rate . The fNIhttp://www.nitrc.org/projects/nirskit/ accessed on 9 December 2022). The recordings from the first and last 15 s were excluded due to potential body movements. We then used detrending and the temporal derivative distribution repair method to reduce data drift and correct artificial motions, respectively [The fNIRS data were preprocessed using NIRS-KIT  signals, which can be represented by the amplitude of low-frequency fluctuations (ALFF) . In parthttps://www.nitrc.org/projects/gretna/ accessed on 12 December 2022). The network organizations were assessed through defined sparsity, which is the number of existing edges divided by the maximum possible number of edges within a network [Graph theory measurements were generated using the GRETNA toolbox  and five were node measurements  .http://www.csie.ntu.edu.tw/~cjlin/libsvm/, accessed on 20 December 2022). Linear regression was used to model the relationship between a dependent variable and one or more independent variables, whose goal is to find the best-fitting line that minimizes the distance between the predicted values and the actual values of the dependent variable. Naive Bayes works by using Bayes’ theorem to calculate the probability of each class label given the values of the input features. Naive Bayes states that the probability of a label given some evidence (the input features) is proportional to the probability of the evidence given the hypothesis multiplied by the prior probability of the hypothesis. Since the small number of participants in this study might undermine the generalizability of the classifier, we employed leave-one-out cross-validation (LOOCV). LOOCV was repeated until data from all participants had been used as the test sample once. The classification performance values from all the repetitions were averaged to obtain the final result. Accuracy was defined as measuring the proportion of correctly classified instances over the total number of instances, and another four metrics, namely, sensitivity, specificity, F1 score, and area-under-the-curve (AUC) value, were used to comprehensively evaluate the performance of the classifier in discriminating HC and CP groups.After the feature selection stage, three well-established supervised machine learning methods were used to construct the classifier. The supervised machine learning algorithms were trained by using a set of input data to produce the desired output. The supervised machine learning algorithms used in this study were linear support vector machines (SVMs), which determined a linear maximum-margin hyperplane to maximize separation between groups. All the machine learning algorithms were implemented in MATLAB , and SVM was conducted using LIBSVM (FDR  <  0.05) between channels 5 and 4 for the HCs.By using resting-state fNIRS data, a group-level correlation matrix was generated for both the CP group and HC group, which was calculated using the mean value of the individual-level correlation matrix. Then, the network strengths between two groups were compared using an independent t-test and corrected. Group-level connectivity differences between the HC and CP groups are shown in t = −2.9683, p = 0.0047, Cohen’s d = 0.8403, power = 0.806, and 93.962% Dorsolateral prefrontal cortex (DLPFC)). However, no significantly decreased zALFF values were detected for the patient group. The findings demonstrate that the brain activation in the PFC of the CP patients was significantly higher than that in the HCs.As demonstrated in T). It was discovered that the σ values of the constructed brain functional networks for both groups were above 1  and other functional network characteristics were calculated for both the CP and HC groups, respectively, and are provided in  above 1 , but theThree machine learning algorithms were tested with respect to their ability to classify CP and HC groups. As shown in Pain is a complex nociceptive stimulus that activates brain regions and networks. Among these brain regions and networks, the PFC plays a vital role in perceiving, modulating, and reappraising pain through various ascending and descending tracts . As propThe current study investigated the resting-state brain activity in CP patients compared to HCs using the ALFF as a measure. The results showed significantly increased zALFF values in channel 8, mainly located in the DLPFC, in CP patients compared to HCs. This finding suggests that CP patients may exhibit hyperactivity in the DLPFC, which is consistent with previous studies that have reported altered prefrontal activity in chronic pain conditions . The DLPInterestingly, our findings demonstrated that the CP patients exhibited abnormal emotional responses and were hypersensitive to pain , leadingThree supervised machine learning classifiers, namely, linear SVM, logistic regression, and naïve bayes, were used to classify CP patients and HCs, achieving at least 75% accuracy and an F1 score of 0.8229 according to the features from the global and local graph measurements. A previous study  used fNIOur study has several limitations. Firstly, it included a limited sample size, which can limit the generalizability of the results. Secondly, the fNIRS technique used in the study has a limited number of channels, which made it difficult to perform regions-of-interest (ROI)-based analysis. Thirdly, the study did not measure the participants’ emotional responses using validated clinical scales, which made it difficult to establish the functional connectivity between the brain regions and the clinical scales.In this study, we discovered significantly weaker functional connectivity and notably higher small-worldness properties of resting-state brain networks in the PFC of the CP groups compared to those of the HCs. The detected alternations in macroscopic PFC organization in the chronic pain patients support our central hypothesis that chronic pain can be characterized according to the type of network disorder, which is defined as altered network organization and connectivity. Additionally, the resting-state fNIRS measurements exhibited excellent performance as screening tools for automatically diagnosing chronic pain patients via supervised machine learning, SVM, logistic regression, and naïve bayes, yielding an F1 score of 0.8229 with only seven features.