Upper-Extremity Nerve Transfers for Sensation: A Systematic Review.

PURPOSE: Sensory nerve transfers may be performed to restore protective sensation and tactile perception after peripheral nerve injury in the upper extremity. There is a paucity of literature on the available donor-recipient configurations for sensory nerve transfers. This article presents a systematic review of reported sensory nerve transfers in the upper extremity. METHODS: Original articles published between 1982 and 2022 were searched in MEDLINE and EMBASE. Articles describing a sensory nerve transfer were included if patient sensory outcomes were reported. Outcomes were categorized according to the modified British Medical Research Council scale, with an outcome of S3 or better defined as satisfactory. RESULTS: Of 1,049 articles, 39 met inclusion and quality criteria. Twenty-seven articles were primary research studies reporting on 197 patients who underwent 11 unique nondigital sensory donor nerve transfers and 24 unique digital donor nerve transfer procedures. The most reliable recipient nerve for restoring sensation to the ulnar border of the small finger was proper ulnar digital nerve of the small finger (38 patients, 89% satisfactory sensory outcome). The best available donors for transfer into the proper ulnar digital nerve of the small finger were proper ulnar digital nerve of the long finger (16 patients, 87.5% good sensory outcome) and palmar cutaneous branch of the median nerve (15 patients, 100% good sensory outcome). To restore sensation along the ulnar border of the thumb and radial aspect of the index finger, the best available donor was the superficial branch of the radial nerve, regardless of transfer into common digital nerve 1 (38 patients, success rate 63%) or directly to proper ulnar digital nerve of the thumb or proper radial digital nerve of the index finger (nine patients, success rates 67%). CONCLUSIONS: Outcomes after sensory nerve transfers are generally good. Surgeons should transfer into a digital nerve recipient when attempting to reconstruct sensation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Supinator to Anterior Interosseous Nerve Transfer to Restore Finger Flexion in Spinal Cord and Peripheral Nerve Injury.

PURPOSE: Restoration of pinch and grasp is a chief concern of patients with cervical spinal cord injury or peripheral nerve injury involving the anterior interosseous nerve (AIN). We hypothesize that supinator nerve-to-AIN (Sup-AIN) nerve transfer is a viable option for AIN neurotization. METHODS: We performed a retrospective review of patients who received Sup-AIN. Reported outcomes included Medical Research Council strength of the flexor digitorum profundus and flexor pollicis longus and passive range of digit motion. Patients with <12 months of follow-up were excluded. RESULTS: Eleven patients underwent Sup-AIN, eight with peripheral nerve injury, and three with spinal cord injury. Three patients were excluded because of insufficient follow-up. Average follow-up was 17 months (range: 12-25 months). Six patients had M4 recovery (75%), one patient had M3 recovery (12.5%), and one did not recover function because of severe stiffness (12.5%). We observed no complications or donor site morbidity in our patients. CONCLUSIONS: The Sup-AIN nerve transfer is an effective option to restore digital flexion in patients with peripheral nerve injury or spinal cord injury involving the AIN motor distribution. In comparison to previously described extensor carpi radialis brevis to AIN and brachialis to AIN nerve transfers, Sup-AIN offers the benefits of a more expendable donor nerve and shorter regenerative distance, respectively. The one failed Sup-AIN in our series highlights the importance of patient selection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Polyethylene Glycol-Fusion Repair of Peripheral Nerve Injuries.

Axons successfully repaired with polyethylene glycol (PEG) fusion tecnology restored axonal continuity thereby preventing their Wallerian degeneration and minimizing muscle atrophy. PEG fusion studies in animal models and preliminary clinical trials involving patients with digital nerve repair have shown promise for this therapeutic approach. PEG fusion is safe to perform, and given the enormous potential benefits, there is no reason not to explore its therapeutic potential.

Growth Factors to Enhance Nerve Regeneration: Approaching Clinical Translation.

Following nerve injury, growth factors (GFs) are transiently upregulated in injured neurons, proliferating Schwann cells, and denervated muscle and skin. They act on these same cells and tissues to promote nerve regeneration and end-organ reinnervation. Consequently, much attention has been focused on developing GF-based therapeutics. A major barrier to clinical translation of GFs is their short half-life. To provide sustained GF treatment to the affected nerve, muscle, and skin in a safe and practical manner, engineered drug delivery systems are needed. This review highlights recent advancements in GF-based therapeutics and discusses the remaining hurdles for clinical translation.

Testosterone Promotes Nerve Tethering and Acellular Biomaterial Perineural Fibrosis in a Rat Wound Repair Model.

Objective: Nerve scarring after traumatic or iatrogenic exposure can lead to impaired function and pain. Nerve-adjacent biomaterials promoting a regenerative tissue response may help reduce perineural fibrosis. Our prior work suggests that testosterone may promote fibrotic skin scarring, but it is unknown how testosterone alters nerve fibrosis or shifts the response to biomaterials. Approach: Sterilized Lewis rats received either testosterone cypionate (+T) or placebo (-T) biweekly. Fifteen days later, wounds were created over the sciatic nerve and covered with an acellular matrix (AM) or closed via primary closure (PC). At day 42, force gauge testing measured the force required to mobilize the nerve, and wound tissue was analyzed. Results: Nerve mobilization force was greater in +T versus -T wounds (p < 0.01). Nerves tore before gliding in 60% of +T versus 6% of -T rats. Epidermal gap (p < 0.01), scar width (p < 0.01), and cross-sectional scar tissue area (p = 0.02) were greater in +T versus -T rats. +T versus -T rats expressed less Col-3 (p = 0.02) and CD68 (p = 0.02). Nerve mobilization force trended nonsignificantly higher for PC versus AM wounds and for +T versus -T wounds within the AM cohort. Innovation: Testosterone increases nerve tethering in the wound healing milieu, altering repair and immune cell balances. Conclusion: Testosterone significantly increases the force required to mobilize nerves in wound beds and elevates histological markers of scarring, suggesting that testosterone-induced inflammation may increase perineural adhesion. Testosterone may reduce the potential anti-tethering protective effect of AM. Androgen receptor antagonism may represent a therapeutic target to reduce scar-related nerve morbidity.

Multidisciplinary strategies to treat painful mononeuropathies in the upper extremity: from lab to bedside.

Neuropathic pain in the upper extremity is a serious problem, commonly involving relatively young patients. The pain causes loss of function and productivity, changes a patient's lifestyle and can progress into a chronic pain syndrome with secondary psychosocial co-morbidities. Treating patients with a painful mononeuropathy remains challenging, with a monodisciplinary approach often having limited treatment efficacy. This narrative review discusses how to deal with this challenge in the treatment of patients with peripheral nerve injury pain, addressing the four important pillars: (1) diagnosing a painful mononeuropathy; (2) clinical pain phenotyping; (3) personalized pain treatment; and (4) using a multidisciplinary team approach.

Nerve-Targeted Surgical Treatments for Spasticity: A Narrative Review.

Spasticity is a potentially debilitating symptom of various acquired and congenital neurologic pathologies that, without adequate treatment, may lead to long-term disability, compromise functional independence, and negatively impact mental health. Several conservative as well as non-nerve targeted surgical strategies have been developed for the treatment of spasticity, but these may be associated with significant drawbacks, such as adverse side effects to medication, device dependence on intrathecal baclofen pumps, and inadequate relief with tendon-based procedures. In these circumstances, patients may benefit from nerve-targeted surgical interventions such as (i) selective dorsal rhizotomy, (ii) hyperselective neurectomy, and (iii) nerve transfer. When selecting the appropriate surgical approach, preoperative patient characteristics, as well as the risks and benefits of nerve-targeted surgical intervention, must be carefully evaluated. Here, we review the current evidence on the efficacy of these nerve-targeted surgical approaches for treating spasticity across various congenital and acquired neurologic pathologies.

A Systematic Review of Registered Clinical Trials for Peripheral Nerve Injuries.

ABSTRACT: Upper extremity peripheral nerve injuries (PNIs) significantly impact daily functionality and necessitate effective treatment strategies. Clinical trials play a crucial role in developing these strategies. However, challenges like retrospective data collection, reporting biases, inconsistent outcome measures, and inadequate data sharing practices hinder effective research and treatment advancements. This review aims to analyze the landscape of reporting, methodological design, outcome measures, and data sharing practices in registered clinical trials concerning upper extremity PNIs. It seeks to guide future research in this vital area by identifying current trends and gaps.A systematic search was conducted on ClinicalTrials.gov and WHO International Clinical Trials Registry Platform up to November 10, 2023, using a combination of MeSH terms and keywords related to upper extremity nerve injury. The PRISMA 2020 guidelines were followed, and the studies were selected based on predefined inclusion and exclusion criteria. A narrative synthesis of findings was performed, with statistical analysis for associations and completion rates.Of 3051 identified studies, 96 met the inclusion criteria. These included 47 randomized controlled trials, 27 nonrandomized trials, and others. Sensory objective measures were the most common primary outcomes. Only 13 studies had a data sharing plan. The analysis revealed varied intervention methods and inconsistencies in outcome measures. There was a significant association between study funding, design, and completion status, but no association between enrollment numbers and completion.This review highlights the need for standardized outcome measures, patient-centered assessments, and improved data sharing in upper extremity PNI trials. The varied nature of interventions and inconsistency in outcome measures indicate the necessity for more rigorous and transparent research practices to strengthen the evidence base for managing these injuries.

Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model.

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied. Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls. Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG's force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001). Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation.

Adipofascial Perforator Flaps for Peripheral Nerve Resurfacing after External Neurolysis.

Background: External neurolysis is an important approach to treating symptomatic peripheral nerve entrapment. In cases of recurrent neurolysis or particularly extensive neurolysis, a paucity of overlying soft tissue for closure over the freshly liberated nerve presents a challenge to long-term surgical success as primary closure of this tissue may predispose the patient to recalcitrant epineural scarring. We report the intermediate term outcomes of the use of adipofascial perforator flaps as a means of vascularised tissue resurfacing of nerves in these difficult scenarios. Methods: We retrospectively reviewed patients undergoing external neurolysis for painful peripheral nerve lesions who subsequently had soft tissue reconstruction with local adipofascial flaps. Data with regard to age, gender, limb involved, duration of symptoms, number of prior surgeries, operative time, type of flap, vascular basis of flap, duration of follow-up, visual analogue pain score, monofilament sensory testing and complications were collected. Results: We included six patients (four women) with a minimum follow-up period of 17 months (range: 17-25 months). Age ranged from 39 to 60 years of age. Four cases involved the upper extremity and two the lower extremity. Symptoms had been present between 1 and 10 years. All operations utilised a local adipofascial flap perfused by a named perforating vessel emanating from an adjacent axial vessel. Operative time for flap creation and inset was 74 minutes, on average. There was one minor complication owing to superficial wound dehiscence. All patients reported substantial pain relief (≥five-point reduction on visual analogue scale; scores 0-3 at last follow-up) and objective sensory testing demonstrated improvement. Conclusions: Our report pays particular attention to surgical technique that is applicable to both upper and lower extremities in addition to intermediate term safety and pain outcomes. Level of Evidence: Level IV (Therapeutic).

Small Joint Denervation of the Hand and Thumb Base: History, Anatomy, Technique, and Outcomes.

Painful arthritis of the small joints of the hand is a common condition affecting older adults, with distal interphalangeal joint and thumb carpometacarpal joint being the two most common locations. Younger adults may also develop painful arthritis after trauma and with inflammatory arthropathy. Traditional surgical approaches address the structure of the joints with either arthrodesis or arthroplasty with or without an implant. In recent decades, denervation has been reported as an alternative treatment for painful small joints that are mobile and stable. Publications on denervation often report faster surgery and recovery times than traditional surgeries that manipulate the small joint bony structures. This article reviews the history, anatomy, surgical techniques, and outcomes of denervation of the small joints of the hand.

Surgical Technique: Brachioradialis to Extensor Carpi Radialis Longus and Brevis Nerve Transfers for Tetraplegia.

Improving upper extremity function in high cervical spinal cord injury (SCI) patients with tetraplegia is a challenging task owing to the limited expendable donor muscles and nerves that are available. Restoring active wrist extension for these patients is critical because it allows for tenodesis grasp. This is classically achieved with brachioradialis (BR) to extensor carpi radialis brevis (ECRB) tendon transfer, but outcomes are suboptimal because BR excursion is insufficient and its origin proximal to the elbow further limits the functionality of the tendon transfer, particularly in the absence of elbow extension. As an alternative approach to restore wrist extension in patients with ICSHT group 1 SCI, we present the first clinical report of the BR to extensor carpi radialis longus (ECRL) and BR to ECRB nerve transfers.

Distal nerve transfers for peripheral nerve injuries: indications and outcomes.

Distal nerve transfer is a refined surgical technique involving the redirection of healthy sacrificable nerves from one part of the body to reinstate function in another area afflicted by paralysis or injury. This approach is particularly valuable when the original nerves are extensively damaged and standard repair methods, such as direct suturing or grafting, may be insufficient. As the nerve coaptation is close to the recipient muscles or skin, distal nerve transfers reduce the time to reinnervation. The harvesting of nerves for transfer should usually result in minimal or no donor morbidity, as any anticipated loss of function is compensated for by adjacent muscles or overlapping cutaneous territory. Recent years have witnessed notable progress in nerve transfer procedures, markedly enhancing the outcomes of upper limb reconstruction for conditions encompassing peripheral nerve, brachial plexus and spinal cord injuries.

Symptomatic Neuroma Development following En Bloc Resection of Skeletal and Soft-Tissue Tumors: A Retrospective Analysis of 331 Cases.

BACKGROUND: Although symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aimed to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. METHODS: The authors retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014 to 2019. The authors included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics, and multivariable regression modeling was performed. RESULTS: The authors included 231 patients undergoing 331 en bloc resections (female, 46%; mean age, 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on examination and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18 to 39 [adjusted OR (aOR), 3.6; 95% CI, 1.5 to 8.4; P < 0.01] and 40 to 64 (aOR, 2.2; 95% CI, 1.1 to 4.6; P = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7 to 5.9; P < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI, 1.2 to 6.0; P = 0.01), and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3 to 1.0; P = 0.045). CONCLUSION: The authors' results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Impact of Upper Limb Motor Recovery on Functional Independence After Traumatic Low Cervical Spinal Cord Injury.

Cervical spinal cord injury (SCI) causes devastating loss of upper limb function and independence. Restoration of upper limb function can have a profound impact on independence and quality of life. In low-cervical SCI (level C5-C8), upper limb function can be restored via reinnervation strategies such as nerve transfer surgery. The translation of recovered upper limb motor function into functional independence in activities of daily living (ADLs), however, remains unknown in low cervical SCI (i.e., tetraplegia). The objective of this study was to evaluate the association of patterns in upper limb motor recovery with functional independence in ADLs. This will then inform prioritization of reinnervation strategies focused to maximize function in patients with tetraplegia. This retrospective study performed a secondary analysis of patients with low cervical (C5-C8) enrolled in the SCI Model Systems (SCIMS) database. Baseline neurological examinations and their association with functional independence in major ADLs-i.e., eating, bladder management, and transfers (bed/wheelchair/chair)-were evaluated. Motor functional recovery was defined as achieving motor strength, in modified research council (MRC) grade, of ≥ 3 /5 at one year from ≤ 2/5 at baseline. The association of motor function recovery with functional independence at one-year follow-up was compared in patients with recovered elbow flexion (C5), wrist extension (C6), elbow extension (C7), and finger flexion (C8). A multi-variable logistic regression analysis, adjusting for known factors influencing recovery after SCI, was performed to evaluate the impact of motor function at one year on a composite outcome of functional independence in major ADLs. Composite outcome was defined as functional independence measure score of 6 or higher (complete independence) in at least two domains among eating, bladder management, and transfers. Between 1992 and 2016, 1090 patients with low cervical SCI and complete neurological/functional measures were included. At baseline, 67% of patients had complete SCI and 33% had incomplete SCI. The majority of patients were dependent in eating, bladder management, and transfers. At one-year follow-up, the largest proportion of patients who recovered motor function in finger flexion (C8) and elbow extension (C7) gained independence in eating, bladder management, and transfers. In multi-variable analysis, patients who had recovered finger flexion (C8) or elbow extension (C7) had higher odds of gaining independence in a composite of major ADLs (odds ratio [OR] = 3.13 and OR = 2.87, respectively, p < 0.001). Age 60 years (OR = 0.44, p = 0.01), and complete SCI (OR = 0.43, p = 0.002) were associated with reduced odds of gaining independence in ADLs. After cervical SCI, finger flexion (C8) and elbow extension (C7) recovery translate into greater independence in eating, bladder management, and transfers. These results can be used to design individualized reinnervation plans to reanimate upper limb function and maximize independence in patients with low cervical SCI.

Neuromuscular implants: Interfacing with skeletal muscle for improved clinical translation of prosthetic limbs.

After an amputation, advanced prosthetic limbs can be used to interface with the nervous system and restore motor function. Despite numerous breakthroughs in the field, many of the recent research advancements have not been widely integrated into clinical practice. This review highlights recent innovations in neuromuscular implants-specifically those that interface with skeletal muscle-which could improve the clinical translation of prosthetic technologies. Skeletal muscle provides a physiologic gateway to harness and amplify signals from the nervous system. Recent surgical advancements in muscle reinnervation surgeries leverage the "bio-amplification" capabilities of muscle, enabling more intuitive control over a greater number of degrees of freedom in prosthetic limbs than previously achieved. We anticipate that state-of-the-art implantable neuromuscular interfaces that integrate well with skeletal muscle and novel surgical interventions will provide a long-term solution for controlling advanced prostheses. Flexible electrodes are expected to play a crucial role in reducing foreign body responses and improving the longevity of the interface. Additionally, innovations in device miniaturization and ongoing exploration of shape memory polymers could simplify surgical procedures for implanting such interfaces. Once implanted, wireless strategies for powering and transferring data from the interface can eliminate bulky external wires, reduce infection risk, and enhance day-to-day usability. By outlining the current limitations of neuromuscular interfaces along with potential future directions, this review aims to guide continued research efforts and future collaborations between engineers and specialists in the field of neuromuscular and musculoskeletal medicine.

Vascularized Denervated Muscle Targets for Headache Surgery-Presentation and Surgical Management.

Patients with substantial trauma to their occipital nerves and those with recurrent or persistent chronic headaches after occipital nerve decompression surgery require transection of their greater occipital and/or lesser occipital nerves to control debilitating pain. Current techniques, such as burying the transected nerve stump in nearby muscle, do not prevent neuroma formation, and more advanced techniques, such as targeted muscle reinnervation and regenerative peripheral nerve interface, have demonstrated only short-term anecdotal success in the context of headache surgery. Vascularized denervated muscle targets (VDMTs) are a novel technique to address the proximal nerve stump after nerve transection that has shown promise to improve chronic nerve pain and prevent neuroma formation. However, VDMTs have not been described in the context of headache surgery. Here authors describe the etiology, workup, and surgical management of 2 patients with recurrent occipital neuralgia who developed vexing neuromas after previous surgery and were successfully treated with VDMTs, remaining pain-free at 3-year follow-up.

Polyethylene Glycol Fusion Restores Axonal Continuity and Improves Return of Function in a Rat Median Nerve Denervation Model.

BACKGROUND: Polyethylene glycol (PEG) can fuse severed closely-apposed axolemmas and restore axonal continuity. We evaluated the effects of PEG-fusion on functional recovery in a rodent forelimb model of peripheral nerve injury. METHODS: The median nerves of male Lewis rats (n=5 per group) were transected and repaired with standard suture repair (SR), SR with PEG (PEG), or SR with PEG and 1% methylene blue (PEG+MB); a sham surgery group was also included. Proximal stimulation produced compound nerve (CAPS) and muscle (CMAPs) action potentials recorded distally. The contralateral limb of each animal acted as an internal control for grip strength measurements. RESULTS: CAPs and CMAPs immediately returned in all PEG and PEG+MB animals, but not in SR animals. PEG and PEG+MB groups demonstrated earlier return of function by post-operative day (POD) 7 (62.6 ±7.3% and 50.9 ±6.7% of contralateral limb grip strength, respectively) compared to SR group, in which minimal return of function was not measurable until POD 21. At POD 98, the PEG group grip strength recovered to 77.2 ±2.8% while the PEG+MB grip strength recovered to 79.9 ±4.4%, compared to 34.9 ±1.8% recovery in the SR group (p<0.05). The PEG and PEG+MB groups reached 50% of the Sham group grip strength on POD 3.8 and 6.3, respectively, whereas the SR group did not reach 50% grip strength recovery of the Sham group throughout the study period. CONCLUSION: PEG-fusion plus neurorrhaphy with or without methylene blue re-established axonal continuity, shortened recovery time, and augmented functional recovery compared to suture neurorrhaphy alone.

Optical absorption spectra and corresponding in vivo photoacoustic visualization of exposed peripheral nerves.

Significance: Multispectral photoacoustic imaging has the potential to identify lipid-rich, myelinated nerve tissue in an interventional or surgical setting (e.g., to guide intraoperative decisions when exposing a nerve during reconstructive surgery by limiting operations to nerves needing repair, with no impact to healthy or regenerating nerves). Lipids have two optical absorption peaks within the NIR-II and NIR-III windows (i.e., 1000 to 1350 nm and 1550 to 1870 nm wavelength ranges, respectively) which can be exploited to obtain photoacoustic images. However, nerve visualization within the NIR-III window is more desirable due to higher lipid absorption peaks and a corresponding valley in the optical absorption of water. Aim: We present the first known optical absorption characterizations, photoacoustic spectral demonstrations, and histological validations to support in vivo photoacoustic nerve imaging in the NIR-III window. Approach: Four in vivo swine peripheral nerves were excised, and the optical absorption spectra of these fresh ex vivo nerves were characterized at wavelengths spanning 800 to 1880 nm, to provide the first known nerve optical absorbance spectra and to enable photoacoustic amplitude spectra characterization with the most optimal wavelength range. Prior to excision, the latter two of the four nerves were surrounded by aqueous, lipid-free, agarose blocks (i.e., 3% w/v agarose) to enhance acoustic coupling during in vivo multispectral photoacoustic imaging using the optimal NIR-III wavelengths (i.e., 1630 to 1850 nm) identified in the ex vivo studies. Results: There was a verified characteristic lipid absorption peak at 1725 nm for each ex vivo nerve. Results additionally suggest that the 1630 to 1850 nm wavelength range can successfully visualize and differentiate lipid-rich nerves from surrounding water-containing and lipid-deficient tissues and materials. Conclusions: Photoacoustic imaging using the optimal wavelengths identified and demonstrated for nerves holds promise for detection of myelination in exposed and isolated nerve tissue during a nerve repair surgery, with possible future implications for other surgeries and other optics-based technologies.