Strategies for Treating Traumatic Neuromas with Tissue-Engineered Materials.

Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include surgical excision and pharmacological management, aiming to alleviate symptoms. However, these approaches often offer temporary relief without addressing the underlying regenerative challenges, necessitating the exploration of advanced strategies such as tissue-engineered materials for more comprehensive and effective solutions. In this study, we discussed the etiology, molecular mechanisms, and histological morphology of traumatic neuromas after peripheral nerve injury. Subsequently, we summarized and analyzed current nonsurgical and surgical treatment options, along with their advantages and disadvantages. Additionally, we emphasized recent advancements in treating traumatic neuromas with tissue-engineered material strategies. By integrating biomaterials, growth factors, cell-based approaches, and electrical stimulation, tissue engineering offers a comprehensive solution surpassing mere symptomatic relief, striving for the structural and functional restoration of damaged nerves. In conclusion, the utilization of tissue-engineered materials has the potential to significantly reduce the risk of neuroma recurrence after surgical treatment.

A small painful neuroma of the transverse cervical nerve treated with pulsed radiofrequency: A case report.

BACKGROUND: Neck pain is a common complaint seen amongst patients from all ages. When common causes of neck pain have been ruled out, it is important to investigate further. A careful physical exam can help identify the painful structures. An ultrasound of the area can also be helpful to identify possible structures involved. Neuromas can be treated with oral medications as well as more invasive techniques, such as pulsed radiofrequency (PRF). CASE DESCRIPTION: In this case report, we discuss a 67-year-old female who presented with left anterior neck pain after developing a cervical mass who was later diagnosed as non-Hodgkin lymphoma. A small neuroma of the left transverse cervical nerve was found on ultrasound and ultimately was treated with PRF with a complete resolution of her symptoms at two months follow-up. CONCLUSION: PRF seems to be a useful tool for controlling neuropathic pain caused by a neuroma.

Musical therapy attenuates neuroma pain by modifying leptin expression.

BACKGROUND: Accumulating evidence reveals that music therapy appears to help patients with pain. However, there is a limited understanding of the underlying mechanisms. Several studies indicate that leptin level has a crucial relationship with acute and chronic pain. Herein, we evaluated the effects of music stimulation and the potential roles of adipokines (leptin) in pain behaviors. METHODS: We used a tibial neuroma transposition (TNT) rat model to mimic neuroma pain. Adult male Sprague-Dawley rats were randomly assigned to one of the three groups (n = 6):group 1 (GC), TNT with white noise; group 2(GM), TNT with music; and group 3(GH), TNT. White noise and music stimulation was given once a day following surgery until the end of the study (42nd day). Pain behavioral tests were carried out before surgery and on the 3rd, 10th, 14th, 21st, 28th, 35th, and 42nd days after surgery. At the end of the observation period, we analyzed the histological samples of blood, spinal cord, and prefrontal cortex to investigate the role of leptin in pain behaviors modulated by white noise and sound stimulation. RESULT: Music therapy might improve the pain of TNT rats. Music stimulation ameliorated paw withdrawal thermal latency (PWTL) from the 3rd day after the surgery while the mechanical pain was improved 21 days after the operation.Music stimulation also increased leptin expression in the spinal cord, prefrontal cortex.White noise had no obvious effect. CONCLUSION: Music therapy might improve the pain of TNT rats. Besides, music stimulation ameliorated TNT-induced pain behaviors and affected leptin expression.

Tratamiento mediante neurólisis ecoguiada con fenol 6 % acuoso del componente álgico por neuromas postamputación: a propósito de un caso / Treatment by ultrasound-guided neurolysis with 6 % aqueous phenol of the pain component for post-amputation neuromas: report of a clinical case

Introducción: El tratamiento del dolor producido por neuromas es en sí complejo. Las opciones de tratamiento una vez se ha descartado la vía quirúrgica son pocas, si bien el impacto que dicho dolor produce en la vida de los pacientes obliga a buscar en estos casos alternativas que ofrezcan un control aceptable del mismo. El objetivo es presentar la neurólisis como una alternativa eficaz para el dolor por neuromas. Caso clínico: Reporte de caso, descriptivo y retrospectivo, de paciente perteneciente al Sistema Nacional de Salud, llevado a cabo por la Unidad de Dolor del Servicio de Anestesiología y Reanimación del Hospital Universitario Joan XXIII.Paciente de 59 años a quien, tras rechazar la cirugía, se le realizó neurólisis ecoguiada con fenol al 6 % acuososo para el tratamiento del dolor por neuromas derivados de la amputación de ambos miembros superiores. Discusión: La infiltración con fenol 6 % acuoso puede llegar a disminuir considerablemente el dolor durante un tiempo igual o superior a los 6 meses, otorgando una mejoría significativa en la calidad de vida de los pacientes.(AU)

Introduction: Magement of pain caused by neuromas is in itself complex. The treatment options once the surgical route has been ruled out are few, although the impact that this pain produces in the lives of patients makes it necessary to look for alternative cases that offer acceptable control of it. The objective is to present neurolysis as an effective alternative for pain due to neuromas. Case report: Descriptive and retrospective case report of a patient belonging to the National Health System, carried out by the Pain Unit of the Anesthesiology and Resuscitation Service of the Hospital Universitario Joan XXIII. 59-year-old patient who, after refusing surgery, underwent ultrasound-guided neurolysis with 6 % aqueous phenol for the treatment of pain due to neuromas derived from the amputation of both upper limbs. Discusion: Infiltration with 6 % aqueous phenol can considerably reduce pain, for a time equal to or greater than 6 months, granting a significant improvement in the quality of life of patients.(AU)

Nonsurgical Approaches to Neuroma Management.

Symptomatic neuromas and chronic neuropathic pain are significant problems affecting patients' quality of life and independence that are challenging to treat. These symptoms are due to structural and functional changes that occur peripherally within neuromas, as well as alterations that occur centrally within the brain and spinal cord. A multimodal approach is most effective, with goals to minimize opioid use, to capitalize on the synergistic effects of nonopioid medications and to explore potential benefits of novel adjunctive treatments.

Incidence, Diagnosis, and Management of Neuromas Following Radiofrequency Ablation Treatment: a Narrative Review.

OBJECTIVE: To determine the epidemiology of neuroma formation as a complication following radiofrequency ablation for chronic pain conditions as well as reviewing the diagnosis and management of neuromas. DESIGN: Evidence-based narrative review and critical appraisal of literature. RESULTS: A comprehensive review of the literature generated one case report describing neuroma formation following lumbar facet medial branch radiofrequency denervation. The rare incidence may be explained by neuroma pathophysiology and peripheral nerve injury produced by radiofrequency ablation, in combination with its asymptomatic nature. Diagnosis of neuromas is predominantly confirmed by clinical history and physical exam with potential for nerve blocks or imaging. Ultrasound has been suggested as a primary imaging modality with magnetic resonance imaging as a secondary option. Neuroma management ranges from conservative therapy to surgery with varying success rates. CONCLUSIONS: Neuroma formation following radiofrequency ablation procedures is exceedingly rare and could be a hypothetical concern in clinical practice. However, the true incidence may be inaccurate given the asymptomatic nature of neuromas.

Effects of 4% Ethanol Sclerosing Injection on Morton's Neuroma: A Histologic Study.

BACKGROUND: Nonoperational treatments for Morton's neuroma remain controversial because it is believed that sclerosing injections do not change nerve fibers on a cellular level. Up to 80% success rates with 4% ethanol sclerosing have been documented, and the remainder required operational removal of the painful nerve. We sought to evaluate the histologic characteristics of Morton's neuromas treated with 4% ethanol sclerosing injection versus corticosteroid injection alone in patients who required removal of the nerve for pain relief. METHODS: A retrospective histologic review was performed of 23 consecutive patients who were treated with either sclerosing injection or nonsclerosing injection and underwent nerve removal between September 1, 2012, and February 28, 2015. RESULTS: Of 19 patients who met the inclusion criteria, eight received sclerosing injections and 11 received nonsclerosing injections. Intraneural fibrosis was more severe in the nonsclerosing injection group (P = .008). CONCLUSION: Histologic changes are seen in Morton's neuroma with the use of 4% ethanol sclerosing injection, contrary to findings from previous studies.

Traumatic neuroma in mastectomy scar: Two case reports and review of the literature.

RATIONALE: Traumatic neuroma is a reparative proliferative response of the nerve after trauma or surgery, which rarely occurs in the breast. However, it must be distinguished from tumor recurrence. PATIENT CONCERNS: A 78-year-old woman underwent left-sided modified radical mastectomy for invasive carcinoma, 7 years before this case. Two painless nodules near the mastectomy scar were discovered in regular follow-up physical examination. A 62-year-old woman had received right-sided modified radical mastectomy for intraductal carcinoma, 4 years before this case. An asymptomatic nodule near the mastectomy scar was detected during follow-up ultrasound (US) examination. DIAGNOSIS: The lesions in both patients were diagnosed as traumatic neuroma. INTERVENTIONS: The first patient underwent excisional biopsy. The second patient underwent US guided core-needle aspiration, followed by conservative therapy. OUTCOMES: Neither patient complained of any discomfort, nor both exhibited normal physical and US findings during follow-up examinations. LESSONS: Newly discovered nodules with the benign imaging features near the mastectomy site of a patient, especially with the tail sign, traumatic neuromas should be taken into consideration. Routine US examination is important for follow-up of breast cancer patients who have undergone mastectomy.

Painful Complications After Cosmetic Surgery: Management of Peripheral Nerve Injury.

BACKGROUND: Aesthetic procedures are among the most common surgeries performed by plastic surgeons. The prevalence of persistent pain remains unknown and underappreciated in the plastic surgery literature. OBJECTIVES: The purpose of this article was to increase awareness of this problem while describing the diagnostic and management strategies for patients with postoperative pain after aesthetic plastic surgery. METHODS: A literature review was performed utilizing the PubMed database to identify painful complications of brachioplasty, blepharoplasty, rhytidectomy, abdominoplasty, breast augmentation, mastopexy, and breast reduction. A treatment algorithm was described to guide plastic surgeons presented with patients reporting pain after aesthetic surgery. RESULTS: Title and abstract review followed by application of inclusion and exclusion criteria resulted in 20 clinical studies for this review, including lateral femoral cutaneous nerve, iliohypogastric nerve, and intercostal nerves after abdominoplasty; median antebrachial cutaneous nerve after brachioplasty; supraorbital, supratrochlear, and infratrochlear nerves after blepharoplasty; greater auricular nerve, auriculotemporal nerve, and zygomaticofacial nerve after rhytidectomy; and intercostobrachial nerve after breast surgery. CONCLUSIONS: Neuromas can be the source of pain following aesthetic surgery. The same clinical and diagnostic approach used for upper and lower extremity neuroma pain can be employed in patients with persistent pain after aesthetic surgery.

Mechanisms and treatment of painful neuromas.

A painful neuroma is a common complication of a peripheral nerve injury or amputation, and it can cause tremendous pain that is resistant to most analgesics. Furthermore, painful neuromas have a high postoperative recurrence rate. Painful neuromas are often accompanied by functional disorders, drastically reducing the patient's quality of life. Several pathophysiological mechanisms have been proposed to explain this type of neuropathic pain, including peripheral and central sensitisation and the involvement of nerve growth factor, α-smooth muscle actin, the cannabinoid CB2 receptor and structural changes in neuroma fibres. Nevertheless, the mechanisms of neuroma-associated pain are not fully understood, contributing to the challenge of managing patients with painful neuromas. There are several effective treatment methods, although none are universally accepted. This review summarises the common mechanisms and treatments of painful neuromas, attempting to link the mechanisms and treatments. We hope to provide useful guidelines for choosing the appropriate treatment for the management of painful neuromas.

Peripheral Interventions for Painful Stump Neuromas of the Lower Limb: A Systematic Review.

OBJECTIVES: Painful stump neuromas in lower limb amputees are a significant burden on a person's quality of life due to interference with wearing prostheses and therefore the ability to walk. Treating painful stump neuromas is a challenge perhaps reflected by the lack of clinical guidelines. MATERIALS AND METHODS: A systematic review was conducted to evaluate the efficacy of all treatments tried in the management of symptomatic neuromas in the lower limb amputation stump in order to establish whether one treatment is superior. RESULTS: Twenty-two studies were included in the final review which examined 14 different treatments both surgical and nonsurgical. Results showed that no single treatment showed superiority. DISCUSSION: The 4 treatments that showed most promise included targeted nerve implantation, traction neurectomy, nerve-to-nerve anastomosis, and perineurial gluing. The short follow-up times and small sample sizes of the studies highlighted the need for more robust clinical studies.

Stromal Vascular Fraction-enriched Fat Grafting for the Treatment of Symptomatic End-neuromata.

The purpose of this study was to methodically illustrate and highlight the crucial steps of stromal vascular fraction (SVF)-enriched fat grafting as a novel treatment of symptomatic end-neuromata of peripheral sensory nerves, and in this study, specifically of the superficial branch of the radial nerve (SBRN). Despite a multitude of existing treatments, persistent postoperative pain and common pain relapse are still very common, independent of the procedure assessed. The neuroma is microsurgically excised accordingly to standardized protocol. Instead of the relocation of the regenerating nerve stump in neighboring anatomical structures, such as muscle or bone, a fat graft is applied perifocally and acts as a mechanical barrier. In order to reduce the fat resorption rate and boost the regenerative potential of the graft, the highly concentrated SVF is integrated in the grafting. The SVF is isolated from subcutaneous fat by enzymatic and mechanic separation of the lipoaspirate by a specific commercial isolation system. The SVF-enriched fat graft provides both a mechanical barrier and various biological effects at the cellular level, including improving angiogenesis, inflammation, and fibrosis. Both mechanical and biologic effects help to reduce the disorganized axonal outgrowth of the nerve stump during nerve regeneration and hence prevent the recurrence of painful end-neuromata.

Unique Considerations in Spinal Cord Stimulator Placement in Pediatrics: A Case Report.

Spinal cord stimulation can be a valuable treatment option in the management of neuropathic pain in select pediatric patients. We present a unique case of a 16-year-old girl with Klippel-Trenaunay-Weber syndrome and scoliosis who required the placement of a spinal cord stimulator (SCS) for severe sciatic nerve neuropathic pain after a right above-knee amputation. Several attempts at lead placement were required before successful pain coverage was achieved because of late recognition of significant vertebral body rotation. This case highlights important considerations in pediatric SCS placement including a careful review of the spinal cord anatomy before the placement of an SCS.

Peripheral Neuromodulation for the Treatment of Postamputation Neuroma Pain: A Case Report.

Neuroma pain can be severe, persistent, and treatment resistant. We present a case of a 37-year-old female amputee who suffered from severe neuroma pain, which had proved resistant to pharmacologic treatment, glycerol injections, spinal cord stimulation, radiofrequency thermocoagulation, and repeated surgical removals. After treatment with peripheral nerve stimulation, using a St. Jude Medical Octrode lead implanted percutaneously under ultrasound guidance close to her painful neuroma, her ongoing pain dramatically decreased from 8 to 3 on a numeric rating scale (0-10). Peripheral neuromodulation is a promising relatively new treatment that can be used for neuroma pain.

Multiple Neuromas Cause Painful "Jumping Stump" in a Transfemoral Amputee: A Case Report.

Painful "jumping stump" is an uncommon but very disturbing complication postamputation. This condition is one of the movement disorder entities resulting from peripheral nerve pathology, often known as "peripherally induced movement disorders." Previously case reports have been written about painful and nonpainful incidence of "jumping stump"; however, only the earliest "jumping stump" article in 1852 suspected that neuromas might influence the involuntary movement. In this study, we describe a 38-year-old man with bilateral transfemoral amputee who suffered from painful "jumping stump" with multiple neuromas confirmed by imaging. He was treated successfully by ultrasound-guided phenol injection into the sciatic neuroma stalks. The pathophysiology of jumping stump and its possible association with neuroma are briefly discussed.

Management of Pain in Complex Nerve Injuries.

Traumatic nerve injuries can be devastating and life-changing events, leading to functional morbidity and psychological stress and social constraints. Even in the event of a successful surgical repair with recovered motor function, pain can result in continued disability and poor quality of life. Pain after nerve injury can also prevent recovery and return to preinjury life. It is difficult to predict which patients will develop persistent pain; once incurred, pain can be even challenging to manage. This review seeks to define the types of pain following peripheral nerve injuries, investigate the pathophysiology and causative factors, and evaluate potential treatment options.

What factors predict the need for further intervention following corticosteroid injection of Morton's neuroma?

BACKGROUND: This study investigated factors that may predict the need for Morton's neuroma (MN) to undergo further treatment within 2 years of a single ultrasound-guided corticosteroid injection. METHODS: A retrospective study was undertaken over a three-year period. The data was stratified into two groups: Group A - did not receive further intervention and Group B - received further treatment. We investigated age, gender, neuroma size and presence of other forefoot pathology or ipsilateral neuromas. RESULTS: 54 patients (57 feet) were reviewed. 29 feet (51%) required further treatment within 2 years (11 repeat injections, 18 surgical excisions). Binary logistic regression showed that larger neuromas (p=0.011) and younger patients (p=0.007) predicted the need for further intervention but not gender (p=0.272). The distribution of concomitant forefoot pathology and ipsilateral neuromas were similar between the two groups. CONCLUSION: Size and age appear to be predictors for further treatment of MN within 2 years of corticosteroid injection.

Ultrasound-Guided Diagnosis and Treatment of Morton's Neuroma.

Morton's neuroma is the fibrous enlargement of the interdigital nerve branches, usually in the second and third interspace between the metatarsal heads where the lateral and medial plantar nerves often join. Specific symptoms are dull or sharp pain, numbness and/or tingling in the third and fourth digits, burning sensation, cramping, and a feeling of "walking on a stone" around the metatarsal heads. Numerous clinical tests for Morton's neuroma have been described, such as thumb index finger squeeze, and Mulder's click and foot squeeze tests. Ultrasound and magnetic resonance imaging can be used for confirmation, especially for differential diagnosis, exact localization, and number of neuromas. Further, performing dynamic imaging during the aforementioned tests is paramount and can readily be carried out with ultrasound. The treatment mainly comprises footwear modifications, radiofrequency ablation, physical therapy, local (corticosteroid and anesthetic) injections into the affected webspace, and surgery. Again the use of real-time ultrasound guidance during such interventions is noteworthy.

Pain Phenotypes and Associated Clinical Risk Factors Following Traumatic Amputation: Results from Veterans Integrated Pain Evaluation Research (VIPER).

OBJECTIVE: To define clinical phenotypes of postamputation pain and identify markers of risk for the development of chronic pain. DESIGN: Cross-sectional study of military service members enrolled 3-18 months after traumatic amputation injury. SETTING: Military Medical Center. SUBJECTS: 124 recent active duty military service members. METHODS: Study subjects completed multiple pain and psychometric questionnaires to assess the qualities of phantom and residual limb pain. Medical records were reviewed to determine the presence/absence of a regional catheter near the time of injury. Subtypes of residual limb pain (somatic, neuroma, and complex regional pain syndrome) were additionally analyzed and associated with clinical risk factors. RESULTS: A majority of enrolled patients (64.5%) reported clinically significant pain (pain score ≥ 3 averaged over previous week). 61% experienced residual limb pain and 58% experienced phantom pain. When analysis of pain subtypes was performed in those with residual limb pain, we found evidence of a sensitized neuroma in 48.7%, somatic pain in 40.8%, and complex regional pain syndrome in 19.7% of individuals. The presence of clinically significant neuropathic residual limb pain was associated with symptoms of PTSD and depression. Neuropathic pain of any severity was associated with symptoms of all four assessed clinical risk factors: depression, PTSD, catastrophizing, and the absence of regional analgesia catheter. CONCLUSIONS: Most military service members in this cohort suffered both phantom and residual limb pain following amputation. Neuroma was a common cause of neuropathic pain in this group. Associated risk factors for significant neuropathic pain included PTSD and depression. PTSD, depression, catastrophizing, and the absence of a regional analgesia catheter were associated with neuropathic pain of any severity.