Selective ansa cervicalis nerve transfer to the marginal mandibular nerve for lower lip reanimation: An anatomical study in cadavers and a case report.

BACKGROUND: Donor nerve options for lower lip reanimation are limited in patients undergoing oncological resection of the facial nerve. The ansa cervicalis nerve (ACN) is an advantageously situated donor with great potential but has not been examined in detail. In the current study, the anatomical technical feasibility of selective ACN to marginal mandibular nerve (MMN) transfer for restoration of lower lip tone and symmetry was explored. A clinical case is presented. METHODS: Dissections were conducted in 21 hemifaces in non-embalmed human cadavers. The maximal harvestable length of ACN was measured and transfer to MMN was simulated. A 28-year-old male underwent ACN-MMN transfer after parotidectomy (carcinoma) and was evaluated 12 months post-operatively (modified Terzis' Lower Lip Grading Scale [25 observers] and photogrammetry). RESULTS: The harvestable length of ACN was 100 ± 12 mm. A clinically significant anatomical variant ("short ansa") was present in 33% of cases (length: 37 ± 12 mm). Tensionless coaptation was possible in all cases only when using a modification of the surgical technique in "short ansa" cases (using an infrahyoid muscle nerve branch as an extension). The post-operative course of the clinical case was uneventful without complications, with improvement in tone, symmetry, and function at the lower lip at 12-month post-operative follow-up. CONCLUSIONS: Selective ACN-MMN nerve transfer is anatomically feasible in facial paralysis following oncological ablative procedures. It allows direct nerve coaptation without significant donor site morbidity. The clinical case showed good outcomes 12 months post-operatively. A strategy when encountering the "short ansa" anatomical variant in clinical cases is proposed.

Aesthetic single-stage vermilion reconstruction using facial artery musculomucosal flap and radial forearm free flap following cancer resection: A case report.

Reconstruction of defects measuring approximately two-thirds of the lower lip width is traditionally reconstructed utilizing loco-regional flap utilizing lip and cheek tissues. This often results in microstomia and unsatisfactory aesthetic outcome. This may hinder the psychosocial aspect of a recovering cancer survivor. Here we describe a single-stage reconstruction in a 79-year-old male patient who received lower lip resection for squamous cell carcinoma. The reconstruction was accomplished using a facial artery musculomucosal flap together with a free radial forearm flap for vermilion and soft tissue defect reconstruction after lip tumor resection with uneventful postoperative course. The patient remains disease-free after 2-year follow-up and does not require revision surgeries for functional or aesthetic reason. This approach may be considered a good option for reconstruction of missing lip and soft tissue simultaneously when the facial vessels are well-preserved during neck dissection. Aesthetically pleasing and functionally satisfactory outcomes may be produced.

Efficacy validation of a lymphatic drainage device for lymphedema drainage in a rat model.

BACKGROUND: Vascularized lymph node transfer (VLNT) is an effective surgery for extremity lymphedema. This study evaluated a lymphatic drainage device (LDD) for the drainage of accumulated fluid into the venous system. METHODS: Micropore filtering membranes with pore sizes of 5, 0.65, and 0.22 µm polyvinylidene difluoride, and 0.8 µm Nylon Net Filter were evaluated to determine the in vitro efficiency of drainage flow of an LDD. The two superior membranes were further used for the evaluation of the inflow and outflow of the LDD in vivo using 5% albumin. RESULTS: At 5 minutes, the volumes drained with 5, 0.65, and 0.22 µm polyvinylidene difluoride and 0.8 µm nylon membranes were 15.2, 2.77, 2.37, and 0.59 mL, respectively (P < .01). At 10 minutes, the collected volumes of 5 and 0.65 µm polyvinylidene difluoride were 1788 and 1051 µL (P = .3). The indocyanine green fluorescence was detected at 50 seconds for the 5 µm polyvinylidene difluoride membrane but not for the 0.65 µm membrane. CONCLUSIONS: The study successfully demonstrated the proof-of-concept of the LDD prototype that mimicked VLNT with drainage of 5% albumin into the venous system in a rat model.

A novel microsurgical rodent model for the transplantation of engineered cardiac muscle flap.

BACKGROUND: The survival of engineered cardiac muscle 'grafts' to the epicardium is limited by vascularization post-transplantation in rat models. In this article, we describe the methodology of a novel rat model that allows for the transplantation of an engineered cardiac muscle flap (ECMF) onto the epicardium. MATERIALS AND METHODS: A total of 40 rats were used. Twenty-four neonatal rats were used to harvest cardiomyocytes. At week 1, ECMF were generated by seeding cardiomyocytes into the arteriovenous loop (AVL) tissue engineering chamber implanted into the right groin of adult rats (n = 8). At week 6, the ECMF were harvested based on a pedicle along the femoral-iliac-abdominal vessel and anastomosed to the neck vessels of the recipient syngeneic adult rats (n = 8). The flaps were delivered into the thoracic cavity and onto the epicardium. The transplanted flaps were harvested at week 10. Survival of the flaps was assessed by the patency of anastomoses and viability of the cardiomyocytes through histological analysis (hematoxylin and eosin [H&E], desmin, and von Willebrand factor [vWF] immunostaining). RESULTS: Six out of 8 rats survived the transplantation procedure. These remaining 6 recipient rats survived until harvest time point at 4 weeks post-transplantation. The mean area of the flap was 46.7mm2 . Six out of 6 flaps harvested at week 10 showed viable cardiomyocytes using desmin immunostaining and vascular channels were seen at the interface between flap and epicardium. CONCLUSION: This is a technically feasible model that will be useful for future assessment of different cardiac stem cell implants and their functional significance in rat heart models.

Simplifying the Decision-Making Process in the Treatment of Kienböck's Disease.

Background In recent years, the classification and treatment algorithm for adult Kienböck's disease (KD) has expanded. However, the priority of the investigations done in determining its management has not been discussed, as not every patient with KD requires magnetic resonance imaging (MRI) or wrist arthroscopy. Materials and Methods We discuss the role of these investigations and emphasize the importance of computed tomography (CT) imaging in evaluating the cortical integrity of the lunate and its role in the decision-making process and management of KD. Results We put forward an investigative algorithm that places into context the investigative roles of MRI, arthroscopy, and CT. Conclusion KD is a rare condition, and there is a lack of comparative studies to help us choose the preferred treatment. The decision on the management options in adult KD may be made by determining the integrity of the lunate cortex and deciding whether the lunate is salvageable or not by CT scan. MRI may provide useful information on the vascular status if the lunate cortex is intact, and the lunate is salvageable. If the lunate is fragmented, it is not salvageable, and MRI does not provide useful information. Arthroscopy has a role in selective cases.

Determining the optimal radiologic wrist and forearm position to visualize screw protrusion in scaphoid fixation.

BACKGROUND: Surgical fixation of scaphoid fractures may result in unrecognized screw protrusion and subsequent cartilage damage to the adjacent joints. The purpose of this study was to use a three-dimensional (3D) scaphoid model to determine the wrist and forearm positioning that will allow intra-operative fluoroscopic visualization of screw protrusions. METHODS: Two 3D scaphoid models, with the wrist in neutral and 20° ulnar deviated, were reconstructed from a cadaveric wrist using the Mimics software. The scaphoid models were divided into three segments and further divided into four quadrants in each of the three segments along the scaphoid axes. Two virtual screws, with a 2 and 1 mm groove from the distal border, were placed so that the screws protrude from each quadrant. The wrist models were rotated along the long axis of the forearm and the angles at which the screw protrusions were visualized were recorded. RESULTS: One-millimetre screw protrusions were visualized at a narrower range of forearm rotation angles compared to 2 mm screw protrusions. One-millimetre screw protrusions in the middle dorsal ulnar quadrant could not be detected. Visualization of the screw protrusion in each quadrant varied with forearm and wrist positioning. CONCLUSION: In this model, all screw protrusions, except 1 mm protrusions in the middle dorsal ulnar quadrant, were visualized with the forearm in pronation, supination or in the mid-pronation position and with the wrist in neutral or 20° ulnar deviated.

Medial Femoral Condyle Corticoperiosteal Flap for Failed Total Wrist Fusions.

Background Recalcitrant nonunion following total wrist arthrodesis is a rare but challenging problem. Most commonly, in the setting of failed fusion after multiple attempts of refixation and cancellous bone grafting, the underlying cause for the failure is invariably multifactorial and is often associated with a range of host issues in addition to poor local soft-tissue and bony vascularity. The vascularized medial femoral condyle corticoperiosteal (MFC-CP) flap has been shown to be a viable option in a variety of similar settings, which provides vascularity and rich osteogenic progenitor cells to a nonunion site, with relatively low morbidity. While its utility has been described for many other anatomical locations throughout the body, its use for the treatment of failed total wrist fusions has not been previously described in detail in the literature. Methods In this article, we outline in detail the surgical technique for MFC-CP flap for the management of recalcitrant aseptic nonunions following failed total wrist arthrodesis. We discuss indications and contraindications, pearls and pitfalls, and potential complications of this technique. Results Two illustrative cases are presented of patients with recalcitrant nonunions following multiple failed total wrist fusions. Conclusion When all avenues have been exhausted, a free vascularized corticoperiosteal flap from the MFC is a sound alternative solution to achieve union, especially when biological healing has been compromised. We have been able to achieve good clinical outcomes and reliable fusion in this difficult patient population.

High throughput, spatially resolved thermal properties measurement using attachable and reusable 3ω sensors.

The 3ω method is a well-established thermal technique used to measure the thermal conductivity of materials and the thermal resistance of interfaces. It has significant advantages over other steady state and transient thermal techniques in its ability to provide spatially resolved thermal property measurements over a wide range of thermal conductivity. Despite its advantages, it has been restricted to lab-scale use because of the difficulty involved in sample preparation and sensor fabrication and is limited to non-metallic substrates. High-throughput 3ω measurements with reusable sensors have not been realized yet. In this work, we demonstrate a method of applying reusable 3ω sensors fabricated on flexible polyimide films to measure bulk and spatially resolved thermal properties. We establish the limits of thermal conductivity measurement with the method to be 1 to 200 W/mK, and within the measurement limit, we verify the method by comparing the measured thermal conductivities of standard samples with established values. From the 3ω measurements, we also determine the thermal resistance of an interlayer of thermal grease as a function of pressure and compare it against the resistance calculated from direct thickness measurements to demonstrate the ability of this method to provide spatially resolved subsurface information. The technique presented is general and applicable to both metallic and non-metallic substrates, providing a method for high-throughput 3ω measurements with reusable sensors and without considerable sample preparation.

Surgical and patient-reported outcomes in an Asian female population with or without adjuvant radiotherapy after immediate free perforator flap breast reconstruction: A retrospective review.

Background: The majority of English literature has reported on the somewhat conflicted outcomes of the effect of radiotherapy on immediate breast reconstruction. However, data specifically related to patients of Asian descent has been scarce. This retrospective study aims to shed light on this topic to aid in the management of this group of patients. Methods: All patients who received immediate free perforator flap-based breast reconstruction under a single surgeon over a 10-year period were included in the study. Patient characteristics, oncological and surgical data were collected. Patients were divided into post-mastectomy radiotherapy (PMRT) and non-PMRT groups. The final aesthetic outcome was assessed by a surgeon-reported outcome questionnaire. Patient satisfaction and psychological outcomes were assessed using validated patient-reported outcome (PRO) questionnaire (BREAST-Q), breast reconstruction, and postoperative module. Results: A total of 101 women, with an average age of 44.7 ± 8.4 underwent perforator flap-based reconstruction. Fifteen patients received PMRT, with remaining 86 patients in the non-PMRT group. The mean duration of follow-up was over 5 years (p = 0.514). The recurrence rate was acceptable in the PMRT group (3/15, p = 0.129). There were no significant differences in complication rates between the two groups (p = 1.000). The aesthetic outcomes were comparable (p = 0.342). PRO appears to be lower in the PMRT group. Conclusions: Immediate breast reconstruction with PMRT in the local patient cohort is oncologically safe, acceptable complication profile, revision rate, and aesthetic outcome. PRO showed lower scores in several categories, which differ from normative data generated in the Western population. Further studies will need to examine the confounding effects of radiation in this specific population.

Early Second Free Flap is Required in Osteoradionecrosis-related Nonunion after Primary Mandible Reconstruction.

Osteoradionecrosis (ORN) manifested as symptomatic nonunion between primary free flap and native mandible after primary bony reconstruction of the mandible is an entity not included in current conventional ORN staging guidelines. This article reports on and proposes early management of this debilitating condition using a chimeric scapular tip free flap (STFF). Methods: A retrospective review was performed examining cases with bony nonunion at the junction of primary free fibula flap (FFF) and native mandible at a single center over a 10-year duration, which required a second free bone flap. Details of each case (patient demographics, oncological details, primary surgery, presentation, and secondary surgery) were documented and analyzed. Outcomes of the treatment were assessed. Results: Four patients (two men and two women; age range, 42-73 years) out of a total of 46 primary FFF were identified. All patients presented with symptoms of low-grade ORN and radiological signs of nonunion. All cases were reconstructed with chimeric STFF. The duration of follow-up ranged from 5 to 20 months. All patients reported resolution of symptoms and radiological evidence of union. Two of four patients subsequently received osseointegrated dental implants. Conclusions: Institutional rate of nonunion after primary FFF requiring a second free bone flap is 8.7%. All the patients of this cohort presented with a similar clinical entity easily discounted as an infected nonunion postosseous flap reconstruction. There is no ORN grading system that currently guides the management of this cohort. Good outcomes are possible with early surgical intervention with a chimeric STFF.

Pro-opiomelanocortin gene delivery suppresses the growth of established Lewis lung carcinoma through a melanocortin-1 receptor-independent pathway.

BACKGROUND: Pro-opiomelanocortin (POMC) is the precursor of several neuropeptides, such as corticotropin, melanocyte-stimulating hormone and the endogenous opioid (ß-endorphin). Our previous studies have indicated that POMC gene delivery inhibited the progression and metastasis of B16-F10 melanoma via the α- melanocyte-stimulating hormone/melanortin-1 receptor (MC-1R) pathway. METHODS: In the present study, the therapeutic efficacy of POMC gene therapy was evaluated in mice bearing established Lewis lung carcinoma (LLC) models both in vitro and in vivo. We also investigated the MC-1R-independent mechanism underlying POMC gene therapy. RESULTS: We found that POMC gene delivery significantly inhibited the growth and colony formation in MC-1R-deficient LLC cells. In addition, POMC gene transfer effectively suppressed the growth of established LLC in mice. The inhibitory mechanisms underlying POMC gene delivery were attibuted to be inhibition of proliferation and the induction of apoptosis. Moreover, POMC gene delivery attenuated tumor ß-catenin signaling by reducing protein levels of ß-catenin and its downstream proto-oncogenes, including cyclin D1 and c-myc. Lastly, POMC gene delivery induced a significant suppression of tumor vasculature. CONCLUSIONS: These results support the existence of an MC-1R-independent pathway for POMC gene therapy, which further expands the therapeutic spectrum of POMC therapy for multiple types of cancer.

In vivo tissue engineering chamber supports human induced pluripotent stem cell survival and rapid differentiation.

Pluripotent stem cells are a potential source of autologous cells for cell and tissue regenerative therapies. They have the ability to renew indefinitely while retaining the capacity to differentiate into all cell types in the body. With developments in cell therapy and tissue engineering these cells may provide an option for treating tissue loss in organs which do not repair themselves. Limitations to clinical translation of pluripotent stem cells include poor cell survival and low cell engraftment in vivo and the risk of teratoma formation when the cells do survive through implantation. In this study, implantation of human induced-pluripotent stem (hiPS) cells, suspended in Matrigel, into an in vivo vascularized tissue engineering chamber in nude rats resulted in substantial engraftment of the cells into the highly vascularized rat tissues formed within the chamber. Differentiation of cells in the chamber environment was shown by teratoma formation, with all three germ lineages evident within 4 weeks. The rate of teratoma formation was higher with partially differentiated hiPS cells (as embryoid bodies) compared to undifferentiated hiPS cells (100% versus 60%). In conclusion, the in vivo vascularized tissue engineering chamber supports the survival through implantation of human iPS cells and their differentiated progeny, as well as a novel platform for rapid teratoma assay screening for pluripotency.

Challenges in the Management of Kidney Allograft Herniation With a Single-stage Pedicled Anterolateral Thigh Flap.

Wound complications are the most common surgical complication after kidney allograft transplantation. Total wound rupture exposing the entire kidney is a rare and not well-described event. We present a successful treatment of this complication in a patient admitted to our unit. A single-stage procedure was performed combining debridement and reconstruction with a pedicled anterolateral thigh flap and an iliotibial band transferring. A short literature review is performed comparing the different treatment strategies and results.

Harvesting the anterolateral thigh flap with non-sizable perforators.

BACKGROUND: The anterolateral thigh flap (ALT) has proven over time to be one of the best reconstructive workhorses due to its versatility and reliability. Without preoperative imaging, vascular anomalies such as having no sizable perforator are sometimes encountered during dissection. We propose a technique, based on a modified version of the traditional myocutaneous ALT to allow harvest of the flap based on non-sizable perforators. This technique can also enable the splitting of a flap when only one sizable perforator is present. METHODS: A retrospective review of patients who received reconstruction with free ALT flap from 2013 to 2019 by the senior author HSS was performed and included all flaps in which non-sizable perforators were harvested. Data collected for analysis included patient demographics, flap size, defect location, inset type, and flap survival. SURGICAL TECHNIQUE: Despite detachment of the majority of skin paddle from the muscle, the flap is harvested with a sleeve of areolar tissue containing preferably more than one non-sizable perforator attached to a small muscular segment of the vastus lateralis containing the pedicle. RESULTS: A total of 349 ALT flaps were performed during the review period by senior author HSS, and 25 flaps were harvested with non-sizable perforator, 10 of which were to enable a split. There were no total losses and 6 partial losses; 2 were amenable to direct closure after debridement, 1 required skin graft, and 3 required a new flap for wound coverage. Incorporating more than one non-sizable perforator increases the reliability of the flap. This technique should be used with caution in patients with multiple underlying comorbidities and when a flow-through flap is required. We were able to achieve primary closure of all donor sites. CONCLUSIONS: It is possible to harvest the anterolateral thigh flap without sizable perforators by conversion to a modified version of the myocutaneous flap. In well-selected patients, using our technique, several non-sizable perforators can reliably perfuse an ALT without the need to use an alternative donor site. This maximizes the number of harvestable ALTs and increases the reconstructive potential by splitting previously "un-splitable" flaps.

The medial sural artery perforator pedicled propeller flap for coverage of middle-third leg defects.

BACKGROUND: Pedicled medial sural artery perforator (MSAP) flap has been described primarily for the coverage of knee and proximal-third leg defects. The technique for reaching the middle third and its use as a retrograde-flow flap were never demonstrated with clarity. This retrospective case-series aimed to report the author's experience in these regards. PATIENTS AND METHODS: Details of all patients who underwent pedicled MSAP flap for lower limb reconstruction over a 7-year period were collected. Surgical outcomes were examined retrospectively. For defects in the anterior middle third of the leg, the "pedicled propeller flap" design was utilized. To determine more distal defects beyond the reach of the anterograde-flow MSAP flap, retrograde-flow pedicled MSAP flaps were used. RESULTS: Eleven anterograde-flow pedicled MSAP flaps were used for defects ranging from the knee to the middle third of the leg. The etiologies of defects included trauma, chronic ulcer, and skin malignancy. All 11 anterograde pedicled MSAP flaps survived and achieved good outcomes. The mean pedicle length was 11.3 cm (range 7-18 cm), and the mean arc length after double pivoting (n = 4) was 29 cm (range 22-36 cm). Of three retrograde-flow pedicled MSAP flaps, two achieved the goal of wound coverage and one suffered complete flap loss. CONCLUSION: The "pedicled propeller flap" design extends the reach of the anterograde-flow pedicled MSAP flap as far as the middle-third anterior leg defects. Our preliminary experience with retrograde-flow MSAP flap has mixed results. Further studies are required to examine its reliability.

Increasing numbers of admissions to the adult burns service at the Royal Adelaide Hospital 2001-2004.

BACKGROUND: The purpose of the study was to illustrate the increasing trend in the number of adult burns patients admitted to the Royal Adelaide Hospital and attempt to explain it and to describe the burn patients admitted to the Royal Adelaide Hospital in terms of age, sex, origin, cause and burn size, particularly since the increasing trend began, in an effort to identify a particular group or burn cause, which may make up a large proportion of the increasing numbers. METHODS: A retrospective review of 1548 acute burn-injured patients using information from the burns unit database between 1996 and 2004 was carried out. RESULTS: Of 1841 total admissions, 1548 were admitted for acute burn injury. There has been an increase in the number of admissions since 2001 amounting to approximately 20% per annum. The cumulative rise in total admissions 2000-2004 is 107% where the increase in acute burn admission in the same period is 82%. There appears to be no difference whether the patient is from a rural or a metropolitan area. Burns of <10% total body surface area constitute most of the increase and are mainly flame and scald injuries. Chemical and contact burns are proportionately increasing. CONCLUSION: The increase in acute admissions is mainly due to the increasing presentation of smaller burns to the unit. The statewide rural burn education programme and media exposure following the 2002 Bali bombings may have contributed to the increase in acute admissions.

Supermicrosurgical replantation of a small amputated nasal tissue in a child.

This study reports a case of an 8-year-old boy who suffered from a dog bite injury to the nose. The amputated nasal tissue measured approximately 1.0 × 1.5 cm and included part of the tip, alar, and soft triangle subunits. Both ends of an artery of less than 0.5 mm were found, and replantation was performed. Chemical leeching was performed postoperatively. At 5-year follow-up, a good aesthetic result was achieved.

An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1ß are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

Transplantation of engineered cardiac muscle flaps in syngeneic rats.

Cardiac tissue engineering offers the prospect of a novel treatment for acquired or congenital heart defects. Previously, our studies have shown a significant mass of vascularized cardiac tissue can be generated using a vascularized tissue engineering chamber approach in nude rats. In this present study, syngeneic rats were investigated as an animal model for cardiac tissue engineering using the arteriovenous loop (AVL) chamber in the presence of a functional immune system. Neonatal cardiomyocytes implanted into the AVL chamber survived and assembled into a contractile flap confirming the basic features we previously showed in growing a cardiac construct. There was no significant loss of the assembled cardiac muscle from immune response. The engineered cardiac muscle flaps (ECMFs) formed were transplanted to the neck vessels of the same animal using a microsurgical technique, and all transplanted tissues remained contractile. The cardiac muscle volume of the control and transplant groups was estimated with histomorphometry using desmin and α-sarcomeric actin immunostaining, and there were no significant differences between the two groups. Finally, utilizing a novel model of transplantation, the ECMFs were transplanted to the heart of a recipient syngeneic rat as a vascularized tissue. The cardiac muscle within the transplanted ECMF was shown to survive and remain contractile for the 4-week post-transplantation period, and importantly, the cardiomyocytes retained the elongated, striated appearance of a mature phenotype. This study demonstrated the proof of concept for transplanting tissue-engineered cardiac muscle as a vascularized cardiac construct.

Glial cell line-derived neurotrophic factor gene transfer exerts protective effect on axons in sciatic nerve following constriction-induced peripheral nerve injury.

Damage to peripheral nerves following trauma or neurodegenerative diseases often results in various sensory and motor abnormalities and chronic neuropathic pain. The loss of neurotrophic factor support has been proposed to contribute to the development of peripheral neuropathy. The main objective of this study was to investigate the protective effect of glial cell line-derived neurotrophic factor (GDNF) using peripheral gene delivery in a rat model of constriction-induced peripheral nerve injury. In this study, it was shown that mechanical and thermal hypersensitivity increased on the injured limb at day 7 after chronic constrictive injury (CCI) was induced. The neurological changes were correlated with the structural changes and loss of GDNF/Akt signaling, particularly in the distal stump of the injured sciatic nerve. Subsequently, recombinant adenovirus was employed to evaluate the potential of intramuscular GDNF gene delivery to alleviate the CCI-induced nerve degeneration ad neuropathic pain. After CCI for 3 days, intramuscular injection of adenovirus encoding GDNF (Ad-GDNF) restored the protein level and activity of GDNF/Akt signaling pathway in the sciatic nerve. This was associated with an improved myelination profile and behavioral outcomes in animals with CCI. In conclusion, the present study demonstrates the involvement of GDNF loss in the pathogenesis of CCI-induced neuropathic pain and the therapeutic potential of intramuscular GDNF gene delivery for the treatment of peripheral nerve degeneration.