Emerging Value of Osseointegration for Intuitive Prosthetic Control after Transhumeral Amputations: A Systematic Review.

Background: Upper extremity limb loss profoundly impacts a patient's quality of life and well-being and carries a significant societal cost. Although osseointegration allows the attachment of the prosthesis directly to the bone, it is a relatively recent development as an alternative to conventional socket prostheses. The objective of this review was to identify reports on osseointegrated prosthetic embodiment for transhumeral amputations and assess the implant systems used, postoperative outcomes, and complications. Methods: A systematic review following PRISMA and AMSTAR guidelines assessed functional outcomes, implant longevity and retention, activities of daily living, and complications associated with osseointegrated prostheses in transhumeral amputees. Results: The literature search yielded 794 articles, with eight of these articles (retrospective analyses and case series) meeting the inclusion criteria. Myoelectric systems equipped with Osseointegrated Prostheses for the Rehabilitation of Amputees implants have been commonly used as transhumeral osseointegration systems. The transhumeral osseointegrated prostheses offered considerable improvements in functional outcomes, with participants demonstrating enhanced range of motion and improved performance of activities compared with traditional socket-based prostheses. One study demonstrated the advantage of an osseointegrated implant as a bidirectional gateway for signal transmission, enabling intuitive control of a bionic hand. Conclusions: Osseointegrated prostheses hold the potential to significantly improve the quality of life for individuals with transhumeral amputations. Continued research and clinical expansion are expected to lead to the realization of enhanced efficacy and safety in this technique, accompanied by cost reductions over time as a result of improved efficiencies and advancements in device design.

Outcomes of Dermal Regeneration Templates in Irradiated and Nonirradiated Scalp Defects.

OBJECTIVES: Dermal regeneration templates (DRTs) are frequently used to treat scalp defects. The aim was to compare the time course of healing for DRTs in scalp defects with and without preoperative radiation. METHODS: The authors conducted a retrospective cohort study of DRT-based scalp reconstruction at 2 academic medical centers between 2013 and 2022. Information was collected on demographic variables, comorbidities, medication use, history of radiation, and DRT outcomes. The primary outcome was DRT loss, defined as exposed calvarium or DRT detachment based on postoperative follow-up documentation. Kaplan-Meier survival analysis and multivariable Cox proportional-hazard regressions were used to compare DRT loss in irradiated and nonirradiated defects. Multivariable logistic regressions were used to compare 30-day postoperative complications (infection, hematoma, or seroma) in irradiated and nonirradiated defects. RESULTS: In total, 158 cases were included. Twenty-eight (18%) patients had a preoperative history of radiation to the scalp. The mean follow-up time after DRT placement was 2.6 months (SD: 4.5 mo). The estimated probability of DRT survival at 2 months was 91% (95% CI: 83%-100%) in nonirradiated patients and 65% (95% CI: 48%-88%) in irradiated patients. In the 55 patients with a bony wound base, preoperative head radiation was associated with a higher likelihood of DRT loss (hazard ratio: 11). Half the irradiated defects experienced uncomplicated total wound closure using Integra Wound Matrix Dressing with or without second-stage reconstruction. CONCLUSIONS: Dermal regeneration template can offer durable coverage in nonirradiated scalp defects. Although DRT loss is more likely in irradiated scalp defects, successful DRT-based reconstruction is possible in select cases.

Neuroma Analysis in Humans: Standardizing Sample Collection and Documentation.

INTRODUCTION: The biology of symptomatic neuromas is poorly understood, particularly the factors causing pain in human neuromas. Pain presence varies among and within individuals, with some having painful and nonpainful neuromas. To bridge these knowledge gaps, our group developed a protocol for assessing neuroma pain and collecting tissue for molecular analysis. This manuscript outlines our workflow and challenges and aims to inspire other centers to share their experiences with these tissues. METHODS: For every included patient and collected nerve or bone tissue specimens, we perform a detailed chart review and a multifaceted analysis of pain and pain perception immediately before surgery. We collect patient-reported outcome measures (PROMs) on pain, function, and mental well-being outcomes at preoperative assessment and at the 6-month follow-up postoperatively. Before surgery, the patient is assessed once again to obtain an immediate preoperative pain status and identify potential differences in pain intensity of different neuromas. Intraoperatively, specimens are obtained and their gross anatomical features are recorded, after which they are stored in paraformaldehyde or frozen for later sample analyses. Postoperatively, patients are contacted to obtain additional postoperative PROMs. RESULTS: A total of 220 specimens of nerve tissue have been successfully obtained from 83 limbs, comprising 95 specimens of neuromas and 125 specimens of nerves located proximal to the neuromas or from controls. CONCLUSIONS: Our approach outlines the methods combining specimen collection and examination, including both macroscopic and molecular biological features, with PROMs, encompassing physical and psychological aspects, along with clinical metadata obtained through clinical teams and chart review.

Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

Preference Signaling and the Integrated Plastic Surgery Match: A National Survey Study.

OBJECTIVE: Rooted in economics market strategies, preference signaling was introduced to the Plastic Surgery Common Application (PSCA) in 2022 for integrated plastic surgery residency applicants. This study surveyed program and applicant experience with preference signaling and assessed how preference signals influenced likelihood of interview invitations. DESIGN: Two online surveys were designed and distributed to all program directors and 2022-2023 applicants to integrated plastic surgery. Opinions regarding the utility of preference signaling were solicited, and the influence of preference signals on likelihood of interview offers was assessed. SETTING: All integrated plastic surgery programs. PARTICIPANTS: All 88 program directors and 2022-2023 applicants to integrated plastic surgery. RESULTS: A total of 45 programs and 99 applicants completed the survey (response rates, 54.2% and 34.2%, respectively). Overall, 79.6% of applicants and 68.9% of programs reported that preference signals were a useful addition to the application cycle. Programs reported that 41.4% of students who sent preference signals received interview offers, compared to 84.6% of home students, 64.8% of away rotators, and 7.1% of other applicants; overall, students who signaled were 5.8 times more likely to receive an interview offer compared to students who were not home students and did not rotate or signal. After multivariable adjustment, programs with higher Doximity rankings, numbers of away rotators, and numbers of integrated residents per year received more preference signals (all p < 0.05). CONCLUSIONS: Applicants and programs report that preference signaling was a useful addition to the integrated plastic surgery application cycle. Sending preference signals resulted in a higher likelihood of interview offers among nonrotators. Preference signaling may be a useful tool to reduce congestion in the integrated plastic surgery application cycle.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Anatomy of the Lumbrical Muscles: Implications for Mechanical Advantage.

BACKGROUND: The lumbrical muscles comprise 4 intrinsic muscles of the hand and are involved in flexion of the metacarpophalangeal joint (MCPJ) and extension of the proximal interphalangeal and distal interphalangeal joints. The purpose of this study was to investigate the anatomical mechanics of the lumbrical muscles of the index, middle, ring, and small fingers. METHODS: We evaluated 25 cadaver arms and measured the distance between the MCPJ and fingertip, the distance between the MCPJ and lumbrical muscle insertion, and the distance between the MCPJ and the most proximal lumbrical muscle origin. With these measurements we calculated the needed force, insertion ratio (length of the proximal, middle, and distal phalanx divided by the MCPJ to insertion distance), and lumbrical muscle length. RESULTS: We found that the force was significantly different between all fingers, except for the comparison of the index and ring finger (P = .34). In addition, we found that muscle length was significantly different between most the fingers, except for the comparison between the index and middle fingers (P = .24), and index and ring fingers (P = .20). There was no significant difference in insertion ratio. CONCLUSIONS: Our study suggests that the anatomical mechanics for the motor function of the lumbrical muscles are similar in all fingers. This could further imply that movements are equally precise in all fingers resulting in coordination with one another and, therefore, adequate hand function. LEVEL OF EVIDENCE: IV.

Heterotopic Ossification Is Associated with Painful Neuromas in Transtibial Amputees Undergoing Surgical Treatment of Symptomatic Neuromas.

BACKGROUND: A relationship between nerve and osseous regeneration has been described. During the surgical treatment of symptomatic neuroma in transtibial amputees, we have noticed that heterotopic ossification (HO) depicted on preoperative radiographs appears to be associated with the location of symptomatic neuromas in both the peroneal and tibial nerve distributions. METHODS: Data were collected for transtibial amputees who underwent surgical management of symptomatic neuroma and were prospectively enrolled from 2018 through 2023. Preoperative radiographs were assessed for the presence of HO located at the distal fibula and tibia. The presence of a peroneal and/or tibial neuroma was based on findings contained within the operative reports. Pain levels were measured on a numeric rating scale (0-10). RESULTS: Sixty-five limbs of 62 amputees were include. Peroneal neuroma and presence of fibular HO (P=0.001), and tibial neuroma and presence of tibial HO (P=0.038) demonstrated an association. The odds of having a symptomatic peroneal neuroma with fibular HO present are greater than the odds of a symptomatic peroneal neuroma when fibular HO is absent (OR 9.3; 95%CI [1.9-45.6], P=0.006). Pre-operative pain scores were significantly higher for all patients with HO (P<0.001), those with fibular HO (P<0.001), and those with tibial HO (P<0.001), compared to patients without HO. CONCLUSIONS: In patients with symptomatic neuromas, preoperative pain was worse when HO was present in the transtibial amputee's residual limb. Further research on the neuroma-HO-complex in symptomatic amputees is required. LEVEL OF EVIDENCE: Therapeutic Level IV.

Three Useful Tips and Tricks for Intraoperative Nerve Stimulation.

Disposable handheld nerve stimulators are widely used in peripheral nerve surgery. Such devices stimulate a motor nerve or the motor component of a mixed nerve by applying electrical current to the proximal region, targeting the main nerve trunk. This stimulation then travels along the motor nerve, reaching the distal end to control the corresponding muscle(s). In this study, the authors demonstrate three useful tips and tricks for handheld nerve stimulation during targeted muscle reinnervation and peripheral nerve surgery. The three tips are (1) identification of proximal muscle contraction by retrograde electrical stimulation of a distal sensory nerve; (2) graded stimulation for identifying motor nerves within fibrotic scarred tissue beds or parallel to the major motor/mixed nerve of interest; and (3) proximal stimulation for validation of adequate post-targeted muscle reinnervation coaptation(s).

Final 1-Year Results of the TUTOR Randomized Trial Comparing Carpal Tunnel Release with Ultrasound Guidance to Mini-open Technique.

Background: Studies comparing carpal tunnel release with ultrasound guidance (CTR-US) to mini-open CTR (mOCTR) are limited. This randomized trial compared the efficacy and safety of these techniques. Methods: In this multicenter randomized trial, patients were randomized (2:1) to unilateral CTR-US or mOCTR. Outcomes included Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and Functional Status Scale (BCTQ-FSS), numeric pain scale (0-10), EuroQoL-5 Dimension 5-Level (EQ-5D-5L), scar outcomes, and complications over 1 year. Results: Patients received CTR-US (n = 94) via wrist incision (mean 6 mm) or mOCTR (n = 28) via palmar incision (mean 22 mm). Comparing CTR-US with mOCTR, the mean changes in BCTQ-SSS (-1.8 versus -1.8; P = 0.96), BCTQ-FSS (-1.0 versus -1.0; P = 0.75), numeric pain scale (-3.9 versus -3.8; P = 0.74), and EQ-5D-5L (0.13 versus 0.12; P = 0.79) over 1 year were comparable between groups. Freedom from scar sensitivity or pain favored CTR-US (95% versus 74%; P = 0.005). Complications occurred in 2.1% versus 3.6% of patients (P = 0.55), all within 3 weeks postprocedure. There was one revision surgery in the CTR-US group, and no revisions for persistent or recurrent symptoms in either group. Conclusions: CTR-US and mOCTR demonstrated similar improvement in carpal tunnel syndrome symptoms and quality of life with comparable low complication rates over 1 year of follow-up. CTR-US was performed with a smaller incision and associated with less scar discomfort.

Usability of Nerve Tape: A Novel Sutureless Nerve Coaptation Device.

PURPOSE: Microsuture neurorrhaphy is technically challenging and has inherent drawbacks. This study evaluated the potential of a novel, sutureless nerve coaptation device to improve efficiency and precision. METHODS: Twelve surgeons participated in this study-six attending hand/microsurgeons and six trainees (orthopedic and plastic surgery residents or hand surgery fellows). Twenty-four cadaver arm specimens were used, and nerve repairs were performed at six sites in each specimen-the median and ulnar nerves in the proximal forearm, the median and ulnar nerves in the distal forearm, and the common digital nerves to the second and third web spaces. Each study participant performed nerve repairs at all six injury locations in two different cadaver arms (n = 12 total repairs for each participating surgeon). The nerve repairs were timed, tested for tensile strength, and graded for alignment and technical repair quality. RESULTS: A substantial reduction in time was required to perform repairs with the novel coaptation device (1.6 ± 0.8 minutes) compared with microsuture (7.2 ± 3.6 minutes). Device repairs were judged clinically acceptable (scoring "Excellent" or "Good" by most of the expert panel) in 97% of the repairs; the percentage of suture repairs receiving Excellent/Good scores by most of the expert panel was 69.4% for attending surgeons and 36.1% for trainees. The device repairs exhibited a higher average peak tensile force (7.0 ± 3.6 N) compared with suture repairs (2.6 ± 1.6 N). CONCLUSIONS: Nerve repairs performed with a novel repair device were performed faster and with higher technical precision than those performed using microsutures. Device repairs had substantially greater tensile strength than microsuture repairs. CLINICAL RELEVANCE: The evaluated novel nerve repair device may improve surgical efficiency and nerve repair quality.

Peripheral neural interfaces: Skeletal muscles are hyper-reinnervated according to the axonal capacity of the surgically rewired nerves.

Advances in robotics have outpaced the capabilities of man-machine interfaces to decipher and transfer neural information to and from prosthetic devices. We emulated clinical scenarios where high- (facial) or low-neural capacity (ulnar) donor nerves were surgically rewired to the sternomastoid muscle, which is controlled by a very small number of motor axons. Using retrograde tracing and electrophysiological assessments, we observed a nearly 15-fold functional hyper-reinnervation of the muscle after high-capacity nerve transfer, demonstrating its capability of generating a multifold of neuromuscular junctions. Moreover, the surgically redirected axons influenced the muscle's physiological characteristics, by altering the expression of myosin heavy-chain types in alignment with the donor nerve. These findings highlight the remarkable capacity of skeletal muscles to act as biological amplifiers of neural information from the spinal cord for governing bionic prostheses, with the potential of expressing high-dimensional neural function for high-information transfer interfaces.

Complications and Unplanned Reoperation After Thumb Metacarpophalangeal Arthrodesis.

PURPOSE: Arthrodesis of the metacarpophalangeal (MCP) joint of the thumb is a common procedure to treat arthritis or instability. Studies reporting hardware complications and nonunion rates after thumb MCP joint arthrodesis report on small sample sizes. We aimed to describe the hardware complication rate, the nonunion rate, and the number of thumbs that achieve union among patients undergoing thumb MCP joint arthrodesis. METHODS: A database spanning 5 urban hospitals in a single metropolitan region in the United States was searched for patients who underwent thumb MCP joint arthrodesis between January 1, 2004 and January 1, 2020. After reviewing patient records, we identified 122 thumbs that underwent MCP joint arthrodesis and had a minimum follow-up of 90 days. The primary outcome was unplanned reoperation after hardware complications and nonunion. Second, the number of thumbs that achieved radiographic union was reported for the tension band and screw fixation arthrodesis group. RESULTS: Twenty-two (18%) out of 122 thumbs had hardware complications after thumb MCP joint arthrodesis, and 11 (9%) out of 122 thumbs developed a nonunion. Patients who underwent screw fixation arthrodesis had no events of hardware complications and subsequent hardware removal. The nonunion rate was 9/65 (14%) in the tension band arthrodesis group and 2 (4%) of 45 in the screw fixation arthrodesis group. Of the thumbs that had available radiographs to assess the healing of the arthrodesis, 34 (81%) of 42 were radiographically united in the tension band arthrodesis group and 29 (91%) of 32 in the screw fixation group. CONCLUSIONS: Our data suggest that screw fixation has fewer hardware complications and a lower reoperation rate than tension band arthrodesis. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

From Data to Decisions: How AI Is Revolutionizing Clinical Prediction Models in Plastic Surgery.

SUMMARY: The impact of clinical prediction models within Artificial Intelligence (AI) and machine learning (ML) is significant. With its ability to analyze vast amounts of data and identify complex patterns, machine learning has the potential to improve and implement evidence-based plastic, reconstructive, and hand surgery. Among others, it is capable of predicting the diagnosis, prognosis, and outcomes of individual patients. This modeling aids daily clinical decision making, most commonly at the moment, as decision-support.Therefore, the purpose of this paper is to provide a practice guideline to plastic surgeons implementing AI in clinical decision-making or setting up AI research to develop clinical prediction models using the 7-step approach and the ABCD validation steps of Steyerberg et al. Secondly, we describe two important protocols which are in the development stage for AI research: 1) the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) checklist, and 2) The PROBAST checklist to access potential biases.

Educating Future Generations of Surgeons across Borders: Novel Global Linked Hybrid Live Cadaveric Peripheral Nerve Surgical Training Course.

Background: This study aimed to evaluate a novel, multi-site, technology-facilitated education and training course in peripheral nerve surgery. The program was developed to address the training gaps in this specialized field by integrating a structured curriculum, high-fidelity cadaveric dissection, and surgical simulation with real-time expert guidance. Methods: A collaboration between the Global Nerve Foundation and Esser Masterclass facilitated the program, which was conducted across three international sites. The curriculum was developed by a panel of experienced peripheral nerve surgeons and included both text-based and multimedia resources. Participants' knowledge and skills were assessed using pre- and postcourse questionnaires. Results: A total of 73 participants from 26 countries enrolled and consented for data usage for research purposes. The professional background was diverse, including hand surgeons, plastic surgeons, orthopedic surgeons, and neurosurgeons. Participants reported significant improvements in knowledge and skills across all covered topics (p < 0.001). The course received a 100% recommendation rate, and 88% confirmed that it met their educational objectives. Conclusions: This study underscores the potential of technology-enabled, collaborative expert-led training programs in overcoming geographical and logistical barriers, setting a new standard for globally accessible, high-quality surgical training. It highlights the practical and logistical challenges of multi-site training, such as time zone differences and participant fatigue. It also provides practical insights for future medical educational endeavors, particularly those that aim to be comprehensive, international, and technologically facilitated.

Technical Variables in Lower Extremity Free Flap Reconstruction.

BACKGROUND: Lower extremity free flap failure rates are higher than in other areas of the body. While prior studies assessed the effect of intraoperative technical variables, these generally investigated individual variables and did not examine relationships between the many individual technical decisions made during free tissue reconstruction. Our purpose was to investigate the effect of variation in intraoperative microsurgical techniques on flap outcomes in a diverse cohort of patients requiring lower extremity free flap coverage. METHODS: Consecutive patients undergoing free flap reconstruction of the lower extremity at two level 1 trauma centers from January 2002 to January 2020 were identified using Current Procedural Terminology codes, followed by a review of medical records. Information regarding demographics and comorbidities, indications, intraoperative technical details, and complications was collected. Outcomes of interest included an unplanned return to the operating room, arterial thrombosis, venous thrombosis, partial flap failure, and total flap failure. Bivariate analysis was performed. RESULTS: In total, 410 patients underwent 420 free tissue transfers. The median follow-up time was 17 months (interquartile ranges: 8.0-37). Total flap failure occurred in 4.9% (n = 20), partial flap failure in 5.9% (n = 24), and unplanned reoperation in 9.0% (n = 37), with arterial thrombosis in 3.2% (n = 13) and venous thrombosis in 5.4% (n = 22). Overall complications were significantly associated with recipient artery choice, with arteries other than PT and AT/DP having a higher rate (p = 0.033), and with arterial revisions (p = 0.010). Total flap failure was also associated with revision of the arterial anastomosis (p = 0.035), and partial flap failure was associated with recipient artery choice (p = 0.032). CONCLUSION: Many interoperative options and techniques are available when performing microvascular lower extremity reconstruction that leads to equally high success rates. However, the use of arterial inflow outside of the posterior tibial and anterior tibial arteries leads to a higher overall complication rate and partial flap failure rate. Intraoperative revision of the arterial anastomosis portends poorly for ultimate flap survival.

Biology and pathophysiology of symptomatic neuromas.

ABSTRACT: Neuromas are a substantial cause of morbidity and reduction in quality of life. This is not only caused by a disruption in motor and sensory function from the underlying nerve injury but also by the debilitating effects of neuropathic pain resulting from symptomatic neuromas. A wide range of surgical and therapeutic modalities have been introduced to mitigate this pain. Nevertheless, no single treatment option has been successful in completely resolving the associated constellation of symptoms. While certain novel surgical techniques have shown promising results in reducing neuroma-derived and phantom limb pain, their effectiveness and the exact mechanism behind their pain-relieving capacities have not yet been defined. Furthermore, surgery has inherent risks, may not be suitable for many patients, and may yet still fail to relieve pain. Therefore, there remains a great clinical need for additional therapeutic modalities to further improve treatment for patients with devastating injuries that lead to symptomatic neuromas. However, the molecular mechanisms and genetic contributions behind the regulatory programs that drive neuroma formation-as well as the resulting neuropathic pain-remain incompletely understood. Here, we review the histopathological features of symptomatic neuromas, our current understanding of the mechanisms that favor neuroma formation, and the putative contributory signals and regulatory programs that facilitate somatic pain, including neurotrophic factors, neuroinflammatory peptides, cytokines, along with transient receptor potential, and ionotropic channels that suggest possible approaches and innovations to identify novel clinical therapeutics.