Spinal Cord Stimulator Implantation for Complex Regional Pain Syndrome in Patient With Extensive Vertebral Surgical History: A Case Report.

Spinal cord stimulation (SCS) has emerged as a novel therapeutic option for refractory complex regional pain syndrome (CRPS). However, SCS placement is often complicated by a prior history of surgical manipulation and hardware implantation along the spinal column. Through this case exploration, we aim to expand the technical approach to SCS implantation in CRPS and encourage further research into innovative approaches for this treatment modality. Our patient is a 61-year-old female with a past medical history of bilateral C7 cervical pedicle fracture status and extensive surgical manipulation, including cervical laminectomy and hardware placement along the cervical spine. The development of CRPS refractory to conventional therapies complicated her course. We obtained non-contrast computed tomography (CT) to confirm intact lamina in vertebral levels below C3 and proceeded with the SCS trial with successful lead placement up to C5. Despite prior surgical manipulation of the vertebral spine hindering our ability to access the ideal C2 level, we were able to achieve significant coverage up to the C5 level. Obtaining non-contrast CT preoperatively and carefully assessing the epidural space patency were integral to our ability to assess the feasibility of lead placement in a patient with extensive hardware. Through this approach, we are able to offer SCS to patients who would otherwise be precluded from this modality.

Persistent pain after total temporomandibular joint replacement surgery: clinical characteristics, comorbidities, and risk factors.

Chronic post-surgical pain (CPSP) after temporomandibular joint (TMJ) surgery is an under-recognized problem. The aim of this study was to document the characteristics of CPSP and identify patient risk factors and comorbidities associated with the development of CPSP after total TMJ replacement (TJR). This was a retrospective cohort study of patients who underwent TJR between 2000 and 2018 at Massachusetts General Hospital, Boston, USA. The primary outcome was the presence of CPSP and use of pain medications after TJR. The secondary outcome was the risk factors associated with the development of CPSP. A total 88 patients were included (79 females, 9 males). The mean follow-up was 4.2 years. Overall, 68 (77.3%) had CPSP and 20 (22.7%) had no CPSP. Of those with CPSP, 32.4% had severe pain and 45.6% continued to take pain medications. Of the 27 patients with data available on the characteristics of the pain, the majority had myofascial pain, while some developed neuropathic pain. A significant difference was noted between the CPSP and non-CPSP groups in terms of preoperative pain, smoking behavior, and use of opioids, non-steroidal anti-inflammatory drugs, muscle relaxants, and neuropathic pain medications.

The Impact of Different Regional Anesthesia Techniques on the Incidence of Chronic Post-surgical Pain in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Network Meta-analysis.

INTRODUCTION: Chronic post-surgical pain (CPSP) remains a prevalent issue following video-assisted thoracic surgery (VATS), despite advancements in surgical techniques. Various regional anesthesia techniques, including thoracic paravertebral block (PVB), intercostal nerve block (ICNB), serratus anterior plane block (SAPB), erector spinae plane block (ESPB), and thoracic epidural anesthesia (TEA), have been employed in VATS procedures to mitigate this issue. This study aims to compare the efficacy of these analgesia methods in reducing the incidence of CPSP in VATS patients through a network meta-analysis. METHODS: A systematic search was conducted in PubMed, the Cochrane Library, and EMBASE for randomized controlled trials (RCTs) comparing the incidence of CPSP associated with PVB, ICNB, SAPB, ESPB, and TEA. The occurrence of CPSP was evaluated at both 2-3 months and 6 months post-surgery. RESULTS: Six RCTs, involving 652 patients, were included in the analysis of CPSP incidence at 2-3 months, while seven RCTs, involving 715 patients, were included for 6 months analysis. PVB, ICNB, or TEA reduced CPSP incidence compared with control group (without regional anesthesia techniques) at both 2-3 months and 6 months post-surgery. However, SAPB was found less effective in reducing CPSP incidence at 2-3 months post-VATS compared to PVB, ICNB, or TEA. CONCLUSIONS: PVB, ICNB, and TEA exhibit significant effects on reducing CPSP incidence following VATS. Conversely, SAPB is not recommended for reducing CPSP incidence post-VATS. Nonetheless, considering the limitation of a small sample size in this network meta-analysis, additional RCTs are necessary to validate these conclusions and enhance the management of CPSP after VATS.

Prognostic clinical prediction models for acute post-surgical pain in adults: a systematic review.

BACKGROUND: Acute post-surgical pain is managed inadequately in many patients undergoing surgery. Several prognostic risk prediction models have been developed to identify patients at high risk of developing moderate to severe acute post-surgical pain. The aim of this systematic review was to describe and evaluate the methodological conduct of these prediction models. METHODS: We searched MEDLINE, EMBASE and CINAHL for studies of prognostic risk prediction models for acute post-surgical pain using predetermined criteria. Prediction model performance was evaluated according to discrimination and calibration. Adherence to TRIPOD guidelines was assessed. Risk of bias and applicability was independently assessed by two reviewers using the prediction model risk of bias assessment tool. RESULTS: We included 14 studies reporting on 17 prediction models. The most common predictors identified in final prediction models included age; surgery type; sex or gender; anxiety or fear of surgery; pre-operative pain intensity; pre-operative analgesic use; pain catastrophising; and expected surgical incision size. Discrimination, measured by the area under receiver operating characteristic curves or c-statistic, ranged from 0.61 to 0.83. Calibration was only reported for seven models. The median (IQR [range]) overall adherence rate to TRIPOD items was 62 (53-66 [47-72])%. All prediction models were at high risk of bias. CONCLUSIONS: Effective prediction models could support the prevention and treatment of acute post-surgical pain; however, existing models are at high risk of bias which may affect their reliability to inform practice. Consideration should be given to the goals, timing of intended use and desired outcomes of a prediction model before development.

A promising alternative to opioids.

A complex extracted from the amniotic membrane in humans reduces post-surgical pain in mice by directly inhibiting pain-sensing neurons.

Delayed Aspiration of Cerebrospinal Fluid From a Thoracic Epidural Catheter After Difficult Placement: A Case Report.

A 69-year-old female with Crohn's disease was admitted for open ileocecectomy with lysis of adhesions. The plan was to proceed with general endotracheal anesthesia and a thoracic epidural catheter for perioperative analgesia. Epidural access was attempted at the T10-11 and T11-12 interspaces, both of which resulted in accidental dural punctures. On the third attempt, the epidural catheter was inserted at the T9-10 interspace. Both the aspiration and test dose were negative. Thirty minutes later, after induction of general anesthesia, the catheter was again aspirated before the epidural pump was connected. Freely flowing, glucose-positive fluid was obtained, and the catheter was removed for the patient's safety. This case suggests that accidental dural puncture may be a risk factor for inappropriate communication with the subarachnoid space. This can be assumed to increase the risk of unanticipated high or total spinal block and its life-threatening sequelae.

Postsurgical tactile-evoked pain: a role for brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent novel tactile corpuscles.

Introduction: Millions of people undergo surgical procedures each year with many developing postsurgical pain. Dynamic allodynia can arise when, for example, clothing brushing close to the surgical site elicits pain. The allodynia circuits that enable crosstalk between afferent tactile inputs and central pain circuits have been studied, but the peripheral tactile drive has not been explored. Objective: Investigate the innervation of the skin in the rat plantar hindpaw skin-muscle incision model. Results: Incision increased epidermal thickness and cell layers and reduced intraepidermal nerve fibre density, identified with PGP9.5 immunostaining. Strikingly, Collagen IV immunostaining revealed the development of dermal protrusions, oriented towards the incision site, that were reminiscent of the dermal papillae that exist in glabrous footpads. S100 immunostaining for lamellar Schwann cells revealed the presence of novel tactile corpuscles (S100-positive bulb) within incision-induced putative dermal papillae. The occurrence of these novel tactile corpuscles coincided with behavioural observations of dynamic allodynia. Tactile corpuscles require brain-derived neurotrophic factor- tropomyosin receptor kinase B (BDNF-TrkB) signalling to form during development, and an increase in BDNF-immunostaining intensity was observed close to the incision site. Local acute administration of TrkB-Fc, to block BDNF-TrkB signalling, reduced, by approximately 50%, both tactile corpuscle size (S100+ bulb area) and dynamic allodynia. Conclusion: Surgery induces the development of novel tactile corpuscles in the incision surround, in a BDNF-TrKB-dependent manner, that contributes to postsurgical tactile-evoked pain.

Intravenous Lidocaine for the Management of Chronic Pain: A Narrative Review of Randomized Clinical Trials.

Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.

Treatment of Refractory Vesicourethral Anastomosis Pain Following Radical Prostatectomy Using a Combination of Non-ablative Erbium:YAG and Neodymium:YAG Laser Therapy: A Case Report.

This case report describes the successful treatment of refractory vesicourethral anastomosis (VUA) pain in an 82-year-old man following radical prostatectomy using a combination of non-ablative erbium:YAG and neodymium:YAG laser therapy with Fotona SP Dynamis. Despite various conventional treatments, the patient's pain persisted, which significantly impaired his quality of life. The rationale for using laser therapy is based on its potential to promote tissue healing and nerve regeneration and reduce inflammation at the anastomosis site. The patient underwent monthly laser irradiation sessions, with the erbium:YAG laser targeting the area around the urethral anastomosis site via the anus and the neodymium:YAG laser irradiating the base of the penis and scrotum. Urethral pain gradually decreased from a visual analog scale score of 10 to 0 over the course of treatment. This highlights the importance of considering alternative approaches when conventional methods fail to provide relief. The targeted, minimally invasive nature of laser therapy may offer a safer and more effective alternative to systemic medications for managing chronic post-surgical pain. Although further research is needed to establish the generalizability and long-term effectiveness of this approach, this case provides a promising foundation for future investigations of the role of laser therapy in managing refractory VUA pain following radical prostatectomy.

Association of Untreated Pre-surgical Depression With Pain and Outcomes After Spinal Surgery.

STUDY DESIGN: Prospective Cohort Study. OBJECTIVE: Untreated pre-surgical depression may prolong post-surgical pain and hinder recovery. However, research on the impact of untreated pre-surgical depression on post-spinal surgery pain is lacking. Therefore, this study aimed to assess pre-surgical depression in patients and analyze its relationship with post-surgical pain and overall post-surgical outcomes. METHODS: We recruited 100 patients scheduled for lumbar spine surgery due to spondylolisthesis, degenerative lumbar disc diseases, and herniated lumbar disc diseases. Psychiatrists evaluated them for the final selection. We assessed the Beck Depression Inventory (BDI), Japanese Orthopaedic Association (JOA), Oswestry Disability Index (ODI), and EuroQoL 5 Dimensions (EQ-5D) scores, numerical back and leg pain scales, and medication dosage data collected before and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Ninety-one patients were included in this study; 40 and 51 were allocated to the control and depression groups, respectively. The pre- and post-surgical leg pain, back pain, and functional scores were not different. However, the depression group showed higher ODI and EQ-5D and lower JOA scores than the control group 3 months post-surgery. Partial correlation analysis revealed an inverse correlation between the JOA and BDI scores and a positive correlation between the EQ-5D and BDI scores at 3 months postoperatively. CONCLUSION: Untreated depression can prolong postoperative pain and hinder recovery. Detecting and treating depression in patients before spine surgery may improve their overall quality of life and functional recovery.

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

A transitional pain management program is associated with reduced opioid dependence after major shoulder surgery.

BACKGROUND: Overprescription of opioids in the United States increases risks of opioid dependence, overdose, and death. Increased perioperative and postoperative opioid use during orthopedic shoulder surgery is a significant risk factor for long-term opioid dependence. The authors hypothesized that a multidisciplinary perioperative pain management program (Transitional Pain Service [TPS]) for major shoulder surgery would lead to a reduced amount of opioids required postoperatively. METHODS: A TPS was implemented at a Veterans Affairs Medical Center focused on nonopioid pain management and cessation support. Opioid consumption during the implementation of the TPS was compared to a historical cohort. All patients undergoing total shoulder arthroplasty (TSA) or rotator cuff repair (RCR) were included. The primary outcome was the proportion of patients continuing opioid use at 90 days postoperatively. Secondary outcomes included postoperative pain scores, time to opioid cessation, and median opioid tablets consumed at 90 days. A multivariable model was developed to predict total opioid use at 90 days postoperatively. Kaplan-Meier curves were calculated for time to opioid cessation. RESULTS: The TPS group demonstrated decreased persistent opioid use at 90 days postdischarge (12.6% vs. 28.6%; P = .018). Independent predictors associated with increased total opioid tablet prescriptions at 90 days included length of stay (ß = 19.17), anxiety diagnosis (ß = 37.627), and number of tablets prescribed at discharge (ß = 1.353). TSA was associated with decreased 90-day opioid utilization (ß = -32.535) when compared to RCR. Median time to cessation was shorter in TSA (6 days) when compared with RCR (8 days). Pain scores were reduced compared with population mean by postdischarge day 2 for TSA and by postdischarge day 7 for RCR. Median number of postdischarge opioid tablets (oxycodone 5 mg) consumed under TPS management was 25 in both RCR and TSA surgery groups (180 morphine milligram equivalents). DISCUSSION AND CONCLUSIONS: This study demonstrates that a TPS reduces the amount of opioid use of patients undergoing shoulder arthroplasty or cuff repair at 90 days when compared with a historical control. Multivariable regression indicated that fewer opioid tablets at discharge was a modifiable factor that may aid in reducing opioid consumption and that anxiety diagnosis, increased length of stay, and cuff repair surgery were other factors independently associated with increased opioid consumption. These data will assist surgeons in counseling patients, setting narcotic use expectations, and minimizing overprescribing. Use of a similar multidisciplinary perioperative pain management program may greatly reduce opioid overprescriptions nationally.

Improving Pain Self-Efficacy in Orthopedic Surgery Patients Through Video-Based Education: A Quality Improvement Project.

BACKGROUND: Effective pain management following discharge is critical for postoperative recovery, with pain self-efficacy serving as a crucial component in this process. Patient education plays a key role in enhancing self-efficacy. Among various educational modalities, a growing body of evidence supports the efficacy of video-based methods. LOCAL PROBLEM: A lack of evidence-based pain education programs for patients undergoing elective orthopedic surgery was identified at an urban academic hospital on the East Coast of the United States. This quality improvement project aimed to develop and assess a video-based pain education program, focusing on pain self-efficacy and self-reported preparedness among adult patients prescribed opioids for postsurgical pain. METHODS: This project adopted a pretest-posttest design, utilizing the knowledge-to-action framework. Data collection spanned 3 months. Among the 69 patients screened for eligibility, 13 participants were included in the analysis. The primary intervention consisted of a 15-minute educational video covering essential pain management aspects. Following the intervention, pain self-efficacy and self-reported preparedness were evaluated using the Pain Self-Efficacy Questionnaire and a five-point Likert scale, respectively. RESULTS: Median (IQR) scores on the Pain Self-Efficacy Questionnaire increased significantly from 20 (16) to 32 (14) (p < .01). Mean (SD) scores for patients' self-reported preparedness also increased from 21.92 (6.53) to 31.85 (2.41) (p < .01). All participants reported being satisfied or very satisfied with the educational intervention. CONCLUSION: Video-based education is a time-efficient and cost-effective approach. Healthcare providers can consider integrating video education to enhance pain self-efficacy in the postoperative phase, thus enhancing postsurgical pain outcomes and overall recovery experience.

Pulsed electromagnetic fields (PEMF) as a valid tool in orthognathic surgery to reduce post-operative pain and swelling: a prospective study.

PURPOSE: PEMF (pulsed electromagnetic fields) founds application in several medical fields to accelerate bone wounds healing and to reduce inflammation. The aim of our study was to evaluate the effectiveness of PEMF in reducing postoperative swelling and pain in patients undergoing orthognathic surgery. METHODS: A prospective observational monocentric study was conducted on a sample of 30 patients undergone to orthognathic surgery in Maxillofacial Surgery Unit of University of Naples Federico II. The patients who followed these inclusion criteria were enrolled in the study: age ≥ 18 years, Class III malocclusion, Surgical procedure of Le Fort I osteotomy + Bilateral Sagittal Split Osteotomy (BSSO), Written informed consent. Patients were divided into two groups: Group SD) postoperative standard treatment with medical therapy and cryotherapy, Group SD + PEMF) postoperative standard therapy + PEMF. Each patient underwent a 3D facial scan, at one (1d) and four (4d) days after surgery to compare the swelling reduction. The pain score was assessed through VAS score and analgesics administration amount. RESULTS: In SD + PEMF group, the facial volume reduction between 1d and 4d scan was on average 56.2 ml (6.23%), while in SD group, it was 23.6 ml (2.63%). The difference between the two groups was 3.6% (p = 0.0168). VAS pain values were significantly higher in SD group compared to SD + PEMF group in the second day after surgery (P = 0.021) and in the total 4 days (P = 0.008). CONCLUSIONS: Our data suggest that PEMF is valid tool to promote faster postoperative swelling and pain reduction in patients undergoing orthognathic surgery.

Standard Opiate Prescribing in Pediatric and Adolescent Gynecologic Surgery to Reduce Opiate Use: Brief Report.

STUDY OBJECTIVE: The aim of this quality improvement (QI) project was to assess postoperative narcotic use after pediatric gynecologic surgeries and establish standard postoperative opioid dosing. Through standard dosing, we hoped to decrease variability in postoperative opioid prescriptions and decrease excess opioid doses in the community. METHODS: This quality improvement project was approved by the Children's Minnesota institutional review board. Counseling on postoperative pain management was provided pre- and postoperatively. At the 2-week postoperative visit, patients were asked about the number of opioid doses used and pain control satisfaction. Baseline data were collected for 6 months, with surgeons prescribing the number of opioid doses on the basis of their personal preference. After reviewing the prescribing practices and number of doses used, standard opioid doses were established, and data collection was repeated. RESULTS: Complete data were recorded for 30 cases before implementation of standard doses and for 29 cases after implementation. Standardized opioid dosing resulted in a 30% decrease in total opioid doses in circulation (252 to 176 doses; P = .014) and a 15% reduction in excess doses in circulation (162 to 137 doses). Forty-three percent of patients did not use any opioid doses. There was no significant difference (P = .8818) in patient pain control satisfaction rating. CONCLUSION: Standard opioid dose prescribing is feasible for common pediatric gynecologic surgeries without affecting patient pain control satisfaction. Opioid dose standardization may decrease opioid circulation within the community. Approximately 2 of every 5 patients used 0 opioid doses, which suggests that a further reduction in the standard dose prescriptions is possible.

Novel Scorpion Toxin ω-Buthitoxin-Hf1a Selectively Inhibits Calcium Influx via CaV3.3 and CaV3.2 and Alleviates Allodynia in a Mouse Model of Acute Postsurgical Pain.

Venom peptides have evolved to target a wide range of membrane proteins through diverse mechanisms of action and structures, providing promising therapeutic leads for diseases, including pain, epilepsy, and cancer, as well as unique probes of ion channel structure-function. In this work, a high-throughput FLIPR window current screening assay on T-type CaV3.2 guided the isolation of a novel peptide named ω-Buthitoxin-Hf1a from scorpion Hottentotta franzwerneri crude venom. At only 10 amino acid residues with one disulfide bond, it is not only the smallest venom peptide known to target T-type CaVs but also the smallest structured scorpion venom peptide yet discovered. Synthetic Hf1a peptides were prepared with C-terminal amidation (Hf1a-NH2) or a free C-terminus (Hf1a-OH). Electrophysiological characterization revealed Hf1a-NH2 to be a concentration-dependent partial inhibitor of CaV3.2 (IC50 = 1.18 µM) and CaV3.3 (IC50 = 0.49 µM) depolarized currents but was ineffective at CaV3.1. Hf1a-OH did not show activity against any of the three T-type subtypes. Additionally, neither form showed activity against N-type CaV2.2 or L-type calcium channels. The three-dimensional structure of Hf1a-NH2 was determined using NMR spectroscopy and used in docking studies to predict its binding site at CaV3.2 and CaV3.3. As both CaV3.2 and CaV3.3 have been implicated in peripheral pain signaling, the analgesic potential of Hf1a-NH2 was explored in vivo in a mouse model of incision-induced acute post-surgical pain. Consistent with this role, Hf1a-NH2 produced antiallodynia in both mechanical and thermal pain.

Opioid use disorder in pediatric populations: considerations for perioperative pain management and precision opioid analgesia.

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain. Studies indicate that lower repetitive methadone doses can decrease the incidence of chronic persistent surgical pain (CPSP). Ongoing research explores genetic components influencing severe surgical pain, inadequate opioid analgesia, and opioid use disorder. This new genetic research coupled with better utilization of opioids in the perioperative setting provides hope in personalizing surgical pain management, reducing pain, opioid use, adverse effects, and helping the fight against the opioid pandemic. EXPERT OPINION: The opioid and analgesic pharmacogenomics approach can proactively 'tailor' a perioperative analgesic plan to each patient based on underlying polygenic risks. This transition from population-based knowledge of pain medicine to individual patient knowledge can transform acute pain medicine and greatly reduce the opioid epidemic's socioeconomic, personal, and psychological strains globally.

Modelled cost-effectiveness analysis of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual care.

BACKGROUND: The aim of the study was to estimate the long-term cost-effectiveness of the Support and Treatment After Replacement (STAR) care pathway for chronic pain after total knee replacement compared with usual postoperative care. METHODS: Study design: A decision-analytic (cohort Markov) model was used for the simulation with time dependent annual transition probabilities and a time horizon of five years. SETTING: Patients treated by National Health Service (NHS) hospitals in England and Wales. STUDY POPULATION: Adults classified as having chronic pain three months after undergoing a total knee replacement. INTERVENTION: The STAR care pathway following a total knee replacement. COMPARATOR: Usual postoperative care following a total knee replacement. PERSPECTIVE: The study was undertaken from the perspective of the NHS. OUTCOME MEASURES: Quality-adjusted life years and healthcare costs. Discounting: A rate of 3.5% for both costs and health utility. RESULTS: Model results indicate that the STAR intervention would dominate current practice by providing a gain in quality-adjusted life years (QALYs) of 0.086 and a reduction of £375 (per person) in costs over the first five years. The incremental net monetary benefit of the STAR intervention was estimated at £2,086 (at a threshold of £20,000 per QALY). Probabilistic sensitivity analysis suggests the STAR intervention is likely to be cost-effective with a probability of 0.62. The results remain robust to changes in model assumptions on comparator utility and the timing of the start of the intervention. If hospital admission costs are assumed not to be reduced by the STAR intervention, it would no longer be cost saving, but it would likely be cost-effective based on probabilistic sensitivity analysis (0.59). CONCLUSION: Evidence from the economic model suggests that the STAR care pathway is likely to be cost-effective and potentially dominant from an NHS perspective. TRIAL REGISTRATION: The STAR trial is registered with ISRCTN, ISRCTN92545361.