Localización biométrica de los puntos motores del músculo cuádriceps femoral de individuos brasileños / Biometric localization of the motor points of the femoral quadriceps muscle of Brazilian individuals

El músculo cuadríceps femoral es un músculo que participa principalmente en los movimientos de la rodilla y también en la cadera, pudiendo ser afectado por alteraciones en el trofismo muscular, tras lesiones de estas articulaciones o afecciones en el tono muscular, como la espasticidad, tras lesiones cerebrovasculares. Cada una de sus cabezas está inervada por ramos del nervio femoral. El presente estudio tuvo por objetivo la identificación y medición de la distancia de los puntos motores (Pm) del músculo cuadríceps femoral, en relación a estructuras anatómicas de relevancia clínica. Se utilizaron 30 miembros inferiores de 23 cadáveres formolizados, de individuos brasileños adultos. El estudio fue realizado en la Universidade Estadual de Ciências da Saúde de Alagoas (UNCISAL), Maceió, Brasil. Se realizó la disección por planos en la zona medial, anterior y lateral del muslo, identificando a los ramos del nervio femoral para cada componente, músculos recto femoral (mRf), vasto medial (mVm), vasto intermedio (mVint) y vasto lateral (mVlat), localizando cada uno de los Pm. Las mediciones se realizaron con un cáliper marca Mitutoyo de 0,05 mm de precisión. Los datos obtenidos fueron tratados estadísticamente, utilizando para ello, el software STATA (versión 14.1). El mRf, tuvo un promedio de 2,45 ± 1,39 Pm, estando la gran mayoría de los Pm (63 %), en la zona distal del tercio proximal del muslo; el mVm presentó 4,42 ± 2,74 Pm en promedio, encontrándose el 41 % de ellos en el tercio medio del muslo, zona distal; el mVint tuvo 3,99 ± 2,34 Pm en promedio y el 58 % de ellos, se localizaron en la zona proximal del tercio medio del muslo; el mVlat presentó un promedio de 3,88 ± 2,37 Pm y el 50 % de éstos se encontraron en del tercio proximal del muslo. La localización biométrica de los Pm se informa en resultados. La ubicación biométrica de los Pm, favorecerá el quehacer, tanto clínico como quirúrgico, de la zona anterior del muslo.

The quadriceps femoris muscle is a muscle that participates mainly in the movements of the knee and also in the hip, being able to be affected by alterations in muscle trophism, after injuries of these joints or muscular tone conditions, such as spasticity, after injuries cerebrovascular. Each of its heads is innervated by branches of the femoral nerve. The objective of this study was to identify and measure the distance of the motor points (MP) of the quadriceps femoris muscle, in relation to anatomical structures of clinical relevance. Thirty lower limbs of 23 formolized corpses of adult Brazilian individuals were used. The study was conducted at the State University of Ciências da Saúde de Alagoas (UNCISAL), Maceió, Brazil. The dissection was performed by planes in the medial, anterior and lateral thigh, identifying the femoral nerve branches for each component, rectus femoris muscles (Rfm), medial vastus (mVm), vastus intermedius (intVm) and vastus lateralis ( latVm), locating each of the MP. The measurements were made with a Mitutoyo caliper of 0.05 mm accuracy. The data obtained were treated statistically, using the STATA software (version 14.1). The Rfm had an average of 2.45 ± 1.39 MP, the great majority of the MP (63 %) being in the distal area of the proximal third of the thigh; the mVm presented 4.42 ± 2.74 MP on average, with 41 % of them in the middle third of the thigh, distal zone; the intVm had 3.99 + 2.34 MP on average and 58 % of them were located in the proximal area of the middle third of the thigh; the latVm presented an average of 3.88 ± 2.37 MP and 50 % of these were found in the proximal third of the thigh. The biometric localization of the MP is reported in results. The biometric location of the MP, will favor the task, both clinical and surgical of the anterior thigh area.

A Prospective Study to Compare Analgesia from Femoral Obturator Nerve Block with Fascia Iliaca Compartment Block for Acute Preoperative Pain in Elderly Patients with Hip Fracture.

BACKGROUND This study aimed to compare femoral obturator nerve block (FONB) with fascia iliaca compartment block (FICB) in the management of acute preoperative pain in elderly patients with hip fracture. MATERIAL AND METHODS Patients ≥65 years (n=154) diagnosed with hip fracture who had surgery within 48 hours of hospital admission included two groups who received ultrasound-guided nerve block, the FONB group (n=77), and the FICB group (n=77). The visual analog scale (VAS) score for pain, requirement for analgesic drugs, nursing care requirements after hospitalization, post-operative complications, and rehabilitation were compared between the FONB and FICB patient groups. RESULTS The VAS scores after both nerve block procedures were significantly reduced compared with those before both nerve block procedures (P<0.05), but there were no differences on the second day after nerve block. The VAS scores at rest and on exercise in the FONB group were significantly lower than those in the FICB group at 30 min and one day after nerve block (P<0.05). The requirement for postoperative analgesic drugs in the FONB group was significantly lower than that in the FICB group (P=0.048). The incidence of nausea and vertigo in the FICB group were significantly higher than in the FONB group (P=0.031 and P=0.034, respectively). Patients in the FONB group experienced significantly improved quality of postoperative function (P=0.029). CONCLUSIONS Both FONB and FICB provided pain control for elderly patients with hip fracture. However, compared with FICB, FONB resulted in significantly improved analgesia with a reduced requirement for analgesic drugs.

A safe percutaneous technique for the reduction of irreducible femoral neck fractures using ultrasound localization of the femoral vascular and nervous structures at the hip.

We present a safe percutaneous technique for the placement of Kirschner wires into the femoral head to assist in the reduction of irreducible femoral neck fractures using ultrasound to identify the vascular and nervous structures about the hip.From January 2011 to June 2014, a total of 36 patients (25 males and 11 females) were enrolled in this study. Patients were placed on a fracture reduction table for limb traction. After 3 unsuccessful reductions with limb traction, ultrasound-guided localization of the patient's femoral artery, vein, and nerve at the hip was performed. These structures were marked on the overlying skin and then Kirschner wires were inserted into the femoral head avoiding these marked structures. After the surgery, the Kirschner wire insertions were routinely reviewed by ultrasound, the hip fracture reduction and the femoral nerve sensorimotor function were routinely examined as well.All 36 patients with an irreducible variant of a femoral neck fracture showed anatomic reduction under C-arm fluoroscopy using ultrasound to avoid K wire injury to the femoral vascular structures and nerve. No major vascular injury during operation. In post-surgical ultrasound examination, local hematoma formation was not evident. There was normal function of the femoral nerve. On follow-up, there were no infections, wound problems, recurrence of fracture displacement, laxity, or implant breakage.Preoperative ultrasonic localization of the femoral artery, vein, and femoral nerve safely allowed. Kirschner wire placement under C-arm fluoroscopy into the femoral head to assist in fracture reduction. This assisted reduction method for irreducible femoral neck fractures had a number of advantages, including closed anatomic reduction with minimal attempts, used simple equipment, and avoided further destruction of the blood supply to the femoral head.

Anatomic implications of lesser trochanterplasty.

OBJECTIVE: The aim of this study was to measure the area of iliopsoas tendon attachment and the distance of sciatic nerve, medial circumflex femoral artery (MCFA) and quadratus muscle to lesser trochanter tip, before and after 5, 10, 15 mm depth excision of lesser trochanter. METHODS: A total 15 hips of 8 adult male cadavers were evaluated. Distances between lesser trochanter tip, sciatic nerve, the lower edge of quadratus muscle and MCFA; length and width of quadratus muscle insertion; area of iliopsoas muscle and quadratus muscle insertion was measured before and after sequential 5,10 and 15 mm depth trochanterplasties using 5 mm wide burr parallel to the posterior cortex. RESULTS: Each incremental 5 mm depth bone removal led to significant decrease of tendon area (p=0.001) at each stage. Mean decreases of iliopsoas tendon attachment area with incremental 5 mm burring were 22%±10 with 5 mm, 50%±13 with 10 mm, and 76% ±13 with 15 mm of burring. CONCLUSION: Up to 15 mm lesser trochanter removal did not result in complete detachment of the iliopsoas tendon. Lesser trochanter tip was detected at least 20 mm away from important anatomic structures including quadratus tendon, sciatic nerve, and the medial circumflex femoral artery.

Local chemical sympathectomy of rat bone marrow and its effect on marrow cell composition.

Existing experimental studies of the effect of sympathetic nerve fibers on bone marrow cells are based on the systemic administration of neurotoxic 6-hydroxydopamine. The method of global chemical sympathectomy has some serious disadvantages and could lead to questionable results. We describe a new method of local chemical sympathectomy of rat femoral bone marrow using guanethidine (Ismelin) delivery using an osmotic mini pump. Local guanethidine treatment for 14days led to complete elimination of sympathetic fibers in femoral bone marrow in contrast to bone marrow of contralateral or naïve femurs. Ablation of sympathetic fibers was associated with a loss of rat endothelial cell marker (RECA) indicating immunophenotype changes in blood vessel endothelial cells, but no significant effect of guanethidine was found on the survival of endothelial cells and mesenchymal stem cells in vitro. Moreover, local guanethidine treatment also elicited a significant reduction of Nestin+/SDF1+ mesenchymal stem cells and c-Kit+/CD90+ hematopoietic stem cells in femoral bone marrow. Tissue-specific chemical sympathectomy of rat bone marrow by guanethidine overcomes some of the drawbacks of systemic administration of neurotoxic compounds like 6-hydroxydopamine and delivers unequivocal evidence on the effects of sympathetic innervation on the cell content of bone marrow.

Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported by Complete Immunohistochemical Loss of H3K27me3.

The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging because of the wide morphological spectrum and suboptimal performance of conventional immunohistochemical markers. MPNST arising primarily in the bone is exceptional, and its definitive diagnosis, particularly out of the neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a highly specific biomarker of MPNSTs. In this article, we report a case of sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The patient was treated with limb-sparing surgery and postoperative radiotherapy. He developed multiple lung and bone metastases 4 months after surgery. Our case confirms the utility of H3K27me3 immunohistochemistry to yield a definitive diagnosis of sporadic MPNST in a rare primary site.

Radiation-Induced Glandular Malignant Peripheral Nerve Sheath Tumor.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors. They can occur in patients with neurofibromatosis type-1 (NF-1) or as sporadic tumors. Only 10% of MPNSTs are radiation induced. Divergent differentiation in MPNSTs can occur in 15% of cases and may include cartilage, bone, skeletal muscle, blood vessels, and very rarely well-formed glands, the latter typically described in NF-1-associated MPNSTs. We report an exceedingly rare case of radiation induced glandular MPNST arising in a neurofibroma of the femoral nerve in a patient previously irradiated for endometrial carcinoma.

The Direct Anterior Approach for Hip Revision: Accessing the Entire Femoral Diaphysis Without Endangering the Nerve Supply.

BACKGROUND: The direct anterior approach (DAA) to the hip has been criticized as an approach that is limited to primary arthroplasty only. Our study objective was to demonstrate, in a cadaveric setting, that an alternate extension of the DAA can be used to reach the femur at the posterior border of the lateral vastus muscle without endangering the nerve supply. METHODS: The iliotibial tract is split anteriorly and pulled laterally, thereby opening the interval to the lateral-posterior aspect of the vastus muscle. The muscle fascia is incised at the posterior border to access the femoral diaphysis. The vastus mobilization is started distally and laterally to the greater trochanter, leaving a muscular bridge between the vastus and the medial gluteal muscle intact. If it is necessary to open the femoral cavity for implant retrieval, we perform an anterior wall osteotomy instead of an extended trochanteric osteotomy. RESULTS: It was possible to split the iliotibial band and pull it laterally, thereby exposing the entire vastus lateralis muscle. The junction of the vastus lateralis and vastus intermedius was not encountered in all cases, nor was the nerve supply with all nerve fibers in that interval. CONCLUSION: The alternate technique described here for accessing the femoral diaphysis allows for easy access to the lateral aspect of the vastus lateralis and the femoral diaphysis. Using this technique, it should also be possible to access the femur and perform all necessary reconstructive procedures on it without damaging the surrounding nerve structures.

Small femoral offset is a risk factor for lateral femoral cutaneous nerve injury during total hip arthroplasty using a direct anterior approach.

INTRODUCTION: Lateral femoral cutaneous nerve (LFCN) injury is a risk specific to the direct anterior approach (DAA) for total hip arthroplasty (THA). However, prevention strategies have not been established. This study aimed to identify the predisposing factors determining LFCN injury during THA via a DAA. HYPOTHESIS: Patients with LFCN injury after THA via DAA would demonstrate predisposing factors. MATERIAL AND METHODS: LFCN injury was identified using a patient questionnaire. Potential factors predisposing to LFCN injury were identified in four categories in patient records: patient factors (age, sex, BMI, diagnosis and range of hip motion), surgical factors (surgical time and surgeon's experience of the DAA), preoperative radiographic factors (neck-shaft angle, femoral offset, acetabular offset, total offset and length of muscle on computed tomography axial image) and radiographic changes (differences between each offset pre- and post-surgery). Multivariate analysis was performed to identify risk factors for LFCN injury during this surgery. RESULTS: After application of inclusion and exclusion criteria, 102 hips (28 with LFCN injury; 74 without) in 102 patients (17 males, 85 females; mean age 66.0 years [range, 26-88 years]) were included. Univariate analysis of patients with and without LFCN injury revealed that small preoperative femoral offset and short preoperative long axis of the tensor fascia lata were statistically significant risk factors for LFCN injury (P=0.004, and P=0.01, respectively). Multivariate analysis showed that small preoperative femoral offset was the only independent risk factor for LFCN injury (odds ratio, 0.895; 95% Confidence Interval, 0.817-0.981; P=0.0018). DISCUSSION: Smaller femoral offset was a significant risk factor for LFCN injury following THA via a DAA. Our recommendations are that careful attention should be paid to the skin-fascia incision and subcutaneous exposure, and that excessive retraction of the sartorius muscle and tensor fascia lata should be avoided, to reduce the risk of LFCN injury in patients with a small femoral offset. LEVEL OF EVIDENCE: IV, retrospective historical cohort study.

NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone.

Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkA(F592A) mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

Long Term Outcome of Conservative Management or Surgical Treatment of Bovine Spastic Paresis: 79 Cases.

OBJECTIVE: To report the long term clinical outcome of calves treated surgically or managed conservatively for bovine spastic paresis of the gastrocnemius (BSP-G), quadriceps femoris muscle (BSP-Q), or mixed muscle involvement (BSP-M). STUDY DESIGN: Retrospective case study. ANIMALS: Calves (n = 79) with bovine spastic paresis. METHODS: Medical records of calves treated by partial tibial neurectomy or managed conservatively for bovine spastic paresis were analyzed for sex, breed, lineage history, and the onset, duration, and severity of clinical signs. Cases were classified as unilateral or bilateral BSP-G, BSP-Q, or BSP-M. Long term follow-up information was obtained by telephone questionnaire. RESULTS: The study group included 26 BSP-G (33%), 16 BSP-Q (20%), and 37 BSP-M (47%) calves. BSP-M and BSP-Q calves were significantly more bilaterally affected compared to BSP-G calves. Twenty-five of 26 BSP-G calves were treated surgically; 86% had complete resolution of clinical signs. Twenty-nine of 37 BSP-M calves were treated surgically; 81.5% improved, but none completely recovered. In all of the conservatively managed BSP-M calves, clinical signs gradually worsened. None of the BSP-Q calves were treated surgically; in 66.7%, clinical signs gradually worsened and 33.3% of calves spontaneously improved. CONCLUSION: Partial tibial neurectomy is advocated for the treatment of BSP-G and in selected cases of BSP-M. However, only partial resolution of clinical signs should be expected for BSP-M. No surgical treatment exists for BSP-Q calves, although spontaneous improvement is possible.

Salicylic acid-based poly(anhydride-ester) nerve guidance conduits: Impact of localized drug release on nerve regeneration.

Nerve guidance conduits (NGCs) can serve as physical scaffolds aligning and supporting regenerating cells while preventing scar tissue formation that often interferes with the regeneration process. Numerous studies have focused on functionalizing NGCs with neurotrophic factors, for example, to support nerve regeneration over longer gaps, but few directly incorporate therapeutic agents. Herein, we fabricated NGCs from a polyanhydride comprised of salicylic acid (SA), a nonsteroidal anti-inflammatory drug, then performed in vitro and in vivo assays. In vitro studies included cytotoxicity, anti-inflammatory response, and NGC porosity measurements. To prepare for implantation, type I collagen hydrogels were used as NGC luminal fillers to further enhance the axonal regeneration process. For the in vivo studies, SA-NGCs were implanted in femoral nerves of mice for 16 weeks and evaluated for functional recovery. The SA-based NGCs functioned as both a drug delivery vehicle capable of reducing inflammation and scar tissue formation because of SA release as well as a tissue scaffold that promotes peripheral nerve regeneration and functional recovery.

Anatomic changes in the macroscopic morphology and microarchitecture of denervated long bone tissue after spinal cord injury in rats.

To study the effects of mechanical loading on bones after SCI, we assessed macro- and microscopic anatomy in rats submitted to passive standing (PS) and electrical stimulation (ES). The study design was based on two main groups of juvenile male Wistar rats with SCI: one was followed for 33 days with therapies starting at day 3 and the other was followed for 63 days with therapies starting at day 33. Both groups were composed of four subgroups (n = 10/group): (1) Sham, (2) SCI, (3) SCI + PS, and (4) SCI + ES. Rehabilitation protocol consisted of a 20-minute session, 3x/wk for 30 days. The animals were sequentially weighed and euthanized. The femur and tibia were assessed macroscopically and microscopically by scanning electronic microscopy (SEM). The SCI rats gained less weight than Sham-operated animals. Significant reduction of bone mass and periosteal radii was observed in the SCI rats, whereas PS and ES efficiently improved the macroscopic parameters. The SEM images showed less and thin trabecular bone in SCI rats. PS and ES efficiently ameliorated the bone microarchitecture deterioration by thickening and increasing the trabeculae. Based on the detrimental changes in bone tissue following SCI, the mechanical loading through weight bearing and muscle contraction may decrease the bone loss and restore the macro- and microanatomy.

Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling.

Microsurgical training with fresh chicken legs.

PURPOSE: With the increasing use of microsurgical techniques in clinical work, regular laboratory training in these techniques has become essential. Several specialized materials have been used for this purpose. We investigated whether effective training could be provided with greater convenience and less expense using fresh chicken thighs. Also, we present the histologic characteristics of chicken femoral neurovascular structures. METHODS: The femoral neurovascular bundles of fresh chicken thighs were dissected. Microanastomosis of vessels and nerves were performed with the aid of a microscope. Tissue from the midthigh of 8 chickens was examined histologically. RESULTS: It was found to reduce the time taken to perform anastomoses using the chicken thigh model with statistically significance. The mean diameters (± standard deviations) of the arteries, veins, and nerves were 2.04 ± 0.17 mm, 1.45 ± 0.06 mm, and 1.24 ± 0.08 mm, respectively. The observed tunica adventitia to media ratio was 1:1 and multiple nerve fascicles were wrapped in a single epineurium. Microsurgery training with this material provides several advantages: ready availability, minimal expense, no scheduling or location limitations, neurorrhaphy training, no need for special facilities for animal care or anesthesia, and no need for the trimming of adventitia. CONCLUSION: The femoral neurovascular bundles of chicken are an appropriate and effective model for teaching and practicing microsurgery.

A new flap design: prefabricated neuro-osseous flap.

We hypothesized that an osseous tissue can be prefabricated with a peripheral nerve by vascular induction, and by using a rat model, we tested this hypothesis.Twenty Wistar rats were used in the prefabricated neuro-osseous flap study. Bilateral sciatic nerves were placed linearly within the medullary cavities of the femurs. Left femurs were accepted as the experimental group. The right femurs of all the rats were used as internal control where the sciatic nerves were ligated at the bony entrance of the flap.After 6 weeks, all experimental femur flaps were viable. Radioactivity counts and metabolic activity studies showed viable and functional bone tissue in experimental group compared with control group (P = 0.001). On microangiographic evaluation, significant dilatation of the perineural vasculature was observed in experimental group. Histologic investigations showed viable bone tissue only in the experimental group flaps.Due to its easy applicability, reproducibility, and robust circulation, the prefabricated neuro-osseous flap would be an option in reconstructive surgery.

The safety and feasibility of a less invasive distal femur closing wedge osteotomy technique: a cadaveric dissection study of the medial aspect of the distal femur.

PURPOSE: To investigate the feasibility and safety of a less invasive surgical approach to the distal medial aspect of the femur in supracondylar medial closing wedge osteotomy for the treatment of lateral compartment osteoarthritis of the knee. The aim of a less invasive approach is to minimize soft tissue disruption, reduce damage to neurovascular structures and thereby prevent muscle atrophy and optimize bone healing potential. METHODS: A human cadaver dissection study on the vascular and neural structures of the medial side of the distal femur was conducted. Surgical dissection (n = 4), cryomicrotomy and subsequent 3D reconstruction of the anatomy (n = 1), and surgical dissection after performance of a supracondylar osteotomy through a less invasive approach (n = 1) were performed in 6 legs in total. RESULTS: The surgical dissection and 3D reconstruction showed that a branch of the femoral artery, the distal genicular artery, supplies the distal area of the vastus medialis (VM) muscle. This artery has several branching patterns; crucial in the presented less invasive approach is its musculo-articular branch, which has an oblique course through the VM to the superomedial pole of the patella. The femoral nerve and saphenous nerve innervate the VM. These structures are at risk in the traditional subvastus approach, whereas no major damage was observed in the leg in which a less invasive approach was performed. CONCLUSIONS: In this cadaveric dissection study, a less invasive approach to the medial side of the distal femur proved to be feasible and safe. Damage to the VM and its neurovascular structures is minimized as compared to the traditional subvastus approach.

Different sympathetic pathways control the metabolism of distinct bone envelopes.

Bone remodeling, the mechanism that modulates bone mass adaptation, is controlled by the sympathetic nervous system through the catecholaminergic pathway. However, resorption in the mandible periosteum envelope is associated with cholinergic Vasoactive Intestinal Peptide (VIP)-positive nerve fibers sensitive to sympathetic neurotoxics, suggesting that different sympathetic pathways may control distinct bone envelopes. In this study, we assessed the role of distinct sympathetic pathways on rat femur and mandible envelopes. To this goal, adult male Wistar rats were chemically sympathectomized or treated with agonists/antagonists of the catecholaminergic and cholinergic pathways; femora and mandibles were sampled. Histomorphometric analysis showed that sympathectomy decreased the number of preosteoclasts and RANKL-expressing osteoblasts in mandible periosteum but had no effect on femur trabecular bone. In contrast, pharmacological stimulation or repression of the catecholaminergic cell receptors impacted the femur trabecular bone and mandible endosteal retromolar zone. VIP treatment of sympathectomized rats rescued the disturbances of the mandible periosteum and alveolar wall whereas the cholinergic pathway had no effect on the catecholaminergic-dependent envelopes. We also found that VIP receptor-1 was weakly expressed in periosteal osteoblasts in the mandible and was increased by VIP treatment, whereas osteoblasts of the retromolar envelope that was innervated only by tyrosine hydroxylase-immunoreactive fibers, constitutively expressed beta-2 adrenergic receptors. These data highlight the complexity of the sympathetic control of bone metabolism. Both the embryological origin of the bone (endochondral for the femur, membranous for the mandibular periosteum and the socket wall) and environmental factors specific to the innervated envelope may influence the phenotype of the sympathetic innervation. We suggest that an origin-dependent imprint of bone cells through osteoblast-nerve interactions determines the type of autonomous system innervating a particular bone envelope.

The majority of myelinated and unmyelinated sensory nerve fibers that innervate bone express the tropomyosin receptor kinase A.

Although skeletal pain is a leading cause of chronic pain and disability, relatively little is known about the specific populations of nerve fibers that innervate the skeleton. Recent studies have reported that therapies blocking nerve growth factor (NGF) or its cognate receptor, tropomyosin receptor kinase A (TrkA) are efficacious in attenuating skeletal pain. A potential factor to consider when assessing the analgesic efficacy of targeting NGF-TrkA signaling in a pain state is the fraction of NGF-responsive TrkA+ nociceptors that innervate the tissue from which the pain is arising, as this innervation and the analgesic efficacy of targeting NGF-TrkA signaling may vary considerably from tissue to tissue. To explore this in the skeleton, tissue slices and whole mount preparations of the normal, adult mouse femur were analyzed using immunohistochemistry and confocal microscopy. Analysis of these preparations revealed that 80% of the unmyelinated/thinly myelinated sensory nerve fibers that express calcitonin gene-related peptide (CGRP) and innervate the periosteum, mineralized bone and bone marrow also express TrkA. Similarly, the majority of myelinated sensory nerve fibers that express neurofilament 200 kDa (NF200) which innervate the periosteum, mineralized bone and bone marrow also co-express TrkA. In the normal femur, the relative density of CGRP+, NF200+ and TrkA+ sensory nerve fibers per unit volume is: periosteum>bone marrow>mineralized bone>cartilage with the respective relative densities being 100:2:0.1:0. The observation that the majority of sensory nerve fibers innervating the skeleton express TrkA+, may in part explain why therapies that block NGF/TrkA pathway are highly efficacious in attenuating skeletal pain.