Results of a Novel Technique for Increasing Bone Contact and Stability in Mandibular Reconstruction with Micro-vascularized Fibula Flap.

Background: Reconstruction of large mandibular defects requires reestablishment of mandibular continuity with bone and soft tissue. The microvascularized fibula flap (MFF) has the advantage of providing both, with adequate length, low resorption rate, low infection risk and possibility of dental implant insertion. It can be adapted to mandibular defects in many different ways. Purpose: This retrospective study will present and evaluate the results of the male-female joint technique for flap positioning and fixation. Methods: The technique consists of designing osteotomies on the binding edge of the MFF and recipient jaw, increasing bone contact from one to five faces. Patients submitted to mandibular reconstruction through this technique were included and evaluated regarding systemic compromise, complication occurrence as well as primary and long-term stability. Results: Ten patients underwent mandibular reconstruction with the male-female joint technique. Sixteen joints were applied, and excluding an early loss due to vascular failure, all remaining 14 joints healed uneventfully. None showed signs of early or late mobility. Conclusion: Fitting the MFF through a male-female joint that provides greater bone contact may improve stability and reduce screw loosening and mini-plate removal rates.

Absence of paresthesia during high-rate spinal cord stimulation reveals importance of synchrony for sensations evoked by electrical stimulation.

Electrically activating mechanoreceptive afferents inhibits pain. However, paresthesia evoked by spinal cord stimulation (SCS) at 40-60 Hz becomes uncomfortable at high pulse amplitudes, limiting SCS "dosage." Kilohertz-frequency SCS produces analgesia without paresthesia and is thought, therefore, not to activate afferent axons. We show that paresthesia is absent not because axons do not spike but because they spike asynchronously. In a pain patient, selectively increasing SCS frequency abolished paresthesia and epidurally recorded evoked compound action potentials (ECAPs). Dependence of ECAP amplitude on SCS frequency was reproduced in pigs, rats, and computer simulations and is explained by overdrive desynchronization: spikes desychronize when axons are stimulated faster than their refractory period. Unlike synchronous spikes, asynchronous spikes fail to produce paresthesia because their transmission to somatosensory cortex is blocked by feedforward inhibition. Our results demonstrate how stimulation frequency impacts synchrony based on axon properties and how synchrony impacts sensation based on circuit properties.

Modelo alternativo para o treinamento de técnicas de microssuturas em "patch" de pericárdio bovino / Alternative model for training microsuture techniques in bovine pericardium patches

Introdução: As técnicas microcirúrgicas caracterizam-se pela aplicação de manobras e suturas em estruturas milimétricas com o auxílio de lentes de aumento. São técnicas complexas, utilizadas em diversas especialidades médicas, que demandam grande habilidade e treinamento antes da aplicação em humanos. O objetivo é desenvolver um modelo de baixo custo e alta fidelidade, para o treinamento de técnicas de microcirurgia, utilizando um fragmento de patch de pericárdio bovino. Método: São utilizados para a confecção deste modelo segmentos remanescentes de uma placa de pericárdio bovino, previamente utilizado em reparos vasculares. O material é recortado em duas partes simétricas e suas extremidades fixadas aos campos cirúrgicos, com auxílio de clamps. A borda superior de cada uma das partes é, então, suturada à borda inferior com fio de Prolene 8-0, de maneira que cada uma forme uma estrutura tubular. Posteriormente, as extremidades tubulares livres passam pela dissecção da camada adventícia e são suturadas entre si, mimetizando uma anastomose vascular término-terminal. Resultados: Com o modelo, simulam-se os mesmos inconvenientes/ dificuldades presentes nas suturas vasculares humanas, como a delaminação de camadas, excesso da camada adventícia e risco de sutura inadvertida da parede posterior, provando sua utilidade na aquisição de habilidades microcirúrgicas básicas, sem necessidade de manipulação de tecidos humanos ou animais. A prática neste modelo pode ocorrer dentro do próprio centro cirúrgico e emprega materiais que seriam descartados. Conclusão: A utilização do pericárdio bovino para confecção de suturas milimétricas mimetiza o tecido vascular humano e é um procedimento de baixo custo, que possibilita o treinamento de habilidades microcirúrgicas.

Introduction: Microsurgical techniques are characterized by the application of maneuvers and sutures to millimetric structures with the aid of magnifying lenses. These are complex techniques, used in various medical specialties, which require great skill and training before applying them to humans. The objective is to develop a lowcost and high-fidelity model for training microsurgery techniques using a fragment of bovine pericardium patch. Method: Remaining segments of a bovine pericardium plate, previously used in vascular repairs, are used to create this model. The material is cut into two symmetrical parts, and its ends are fixed to the surgical drapes with the aid of clamps. The upper edge of each part is then sutured to the lower edge with 8-0 Prolene thread so that each one forms a tubular structure. Subsequently, the free tubular ends undergo dissection of the adventitial layer and are sutured together, mimicking an end-to-end vascular anastomosis. Results: With the model, the same inconveniences/ difficulties present in human vascular sutures are simulated, such as delamination of layers, excess of the adventitial layer, and risk of inadvertent suturing of the posterior wall, proving its usefulness in the acquisition of basic microsurgical skills, without need to manipulate human or animal tissues. Practice in this model can take place within the surgical center itself and uses materials that would otherwise be discarded. Conclusion: The use of bovine pericardium to create millimetric sutures mimics human vascular tissue and is a low-cost procedure that allows the training of microsurgical skills.

Therapeutic exercise interventions in rat models of arthritis.

Arthritis is the leading cause of musculoskeletal pain and disability worldwide. Nearly 50% of individuals over the age of 65 have arthritis, which contributes to limited function, articular pain, physical inactivity, and diminished quality of life. Therapeutic exercise is often recommended in clinical settings for patients experiencing arthritic pain, however, there is little practical guidance regarding the use of therapeutic exercise to alleviate arthritic musculoskeletal pain. Rodent models of arthritis allow researchers to control experimental variables, which cannot be done with human participants, providing an opportunity to test therapeutic approaches in preclinical models. This literature review provides a summary of published findings in therapeutic exercise interventions in rat models of arthritis as well as gaps in the existing literature. We reveal that preclinical research in this field has yet to adequately investigate the impact of experimental variables in therapeutic exercise including their modality, intensity, duration, and frequency on joint pathophysiology and pain outcomes.

Modulating the activity of human nociceptors with a SCN10A promoter-specific viral vector tool.

Despite the high prevalence of chronic pain as a disease in our society, there is a lack of effective treatment options for patients living with this condition. Gene therapies using recombinant AAVs are a direct method to selectively express genes of interest in target cells with the potential of, in the case of nociceptors, reducing neuronal firing in pain conditions. We designed a recombinant AAV vector expressing cargos whose expression was driven by a portion of the SCN10A (NaV1.8) promoter, which is predominantly active in nociceptors. We validated its specificity for nociceptors in mouse and human dorsal root ganglia and showed that it can drive the expression of functional proteins. Our viral vector and promoter package drove the expression of both excitatory or inhibitory DREADDs in primary human DRG cultures and in whole cell electrophysiology experiments, increased or decreased neuronal firing, respectively. Taken together, we present a novel viral tool that drives expression of cargo specifically in human nociceptors. This will allow for future specific studies of human nociceptor properties as well as pave the way for potential future gene therapies for chronic pain.

Time-dependent and selective microglia-mediated removal of spinal synapses in neuropathic pain.

Neuropathic pain is a debilitating condition resulting from damage to the nervous system. Imbalance of spinal excitation and inhibition has been proposed to contribute to neuropathic pain. However, the structural basis of this imbalance remains unknown. Using a preclinical model of neuropathic pain, we show that microglia selectively engulf spinal synapses that are formed by central neurons and spare those of peripheral sensory neurons. Furthermore, we reveal that removal of inhibitory and excitatory synapses exhibits distinct temporal patterns, in which microglia-mediated inhibitory synapse removal precedes excitatory synapse removal. We also find selective and gradual increase in complement depositions on dorsal horn synapses that corresponds to the temporal pattern of microglial synapse pruning activity and type-specific synapse loss. Together, these results define a specific role for microglia in the progression of neuropathic pain pathogenesis and implicate these immune cells in structural remodeling of dorsal horn circuitry.

Distinct and sex-specific expression of mu opioid receptors in anterior cingulate and somatosensory S1 cortical areas.

ABSTRACT: The anterior cingulate cortex (ACC) processes the affective component of pain, whereas the primary somatosensory cortex (S1) is involved in its sensory-discriminative component. Injection of morphine in the ACC has been reported to be analgesic, and endogenous opioids in this area are required for pain relief. Mu opioid receptors (MORs) are expressed in both ACC and S1; however, the identity of MOR-expressing cortical neurons remains unknown. Using the Oprm1-mCherry mouse line, we performed selective patch clamp recordings of MOR+ neurons, as well as immunohistochemistry with validated neuronal markers, to determine the identity and laminar distribution of MOR+ neurons in ACC and S1. We found that the electrophysiological signatures of MOR+ neurons differ significantly between these 2 areas, with interneuron-like firing patterns more frequent in ACC. While MOR+ somatostatin interneurons are more prominent in ACC, MOR+ excitatory neurons and MOR+ parvalbumin interneurons are more prominent in S1. Our results suggest a differential contribution of MOR-mediated modulation to ACC and S1 outputs. We also found that females had a greater density of MOR+ neurons compared with males in both areas. In summary, we conclude that MOR-dependent opioidergic signaling in the cortex displays sexual dimorphisms and likely evolved to meet the distinct function of pain-processing circuits in limbic and sensory cortical areas.

Síndrome autoimune induzida por adjuvantes desencadeada por implantes mamários de silicone: revisão sistemática / Adjuvant-induced autoimmune syndrome triggered by silicone breast implants: systematic review

A síndrome autoimune induzida por adjuvantes (ASIA) e seus critérios diagnósticos foram descritos por Shoenfeld em 2011, relacionando sintomas de autoimunidade a adjuvantes, como o silicone, presente em próteses mamárias. Essa revisão sistemática objetivou reunir dados da literatura sobre a sintomatologia, a incidência e os tratamentos propostos para ASIA causada por implantes mamários de silicone (IMS). Foram realizadas pesquisas nas bases de dados PubMed, LILACS, Embase e Cochrane, utilizando os descritores "Autoimmune Syndrome Induced by Adjuvants", "Breast implant" e "Silicone Implant Incompatibility Syndrome". A estratégia de busca gerou 95 artigos, dos quais 20 foram incluídos na revisão. São as três as principais teorias sugeridas pelos autores para explicar o desenvolvimento da síndrome: predisposição genética, silicone bleeding e a formação de uma cápsula periprótese. As manifestações clínicas mais frequentemente descritas incluem fadiga crônica, artralgia, mialgia, distúrbios cognitivos e do sono. Não há consenso sobre os achados laboratoriais e os fatores de risco associados, além disso, estudos recentes propõem a ampliação dos critérios diagnósticos inicialmente descritos. O tratamento adequado permanece controverso, envolvendo desde o uso de medicações até o explante da prótese. Apesar dos artigos revisados sugerirem a existência da ASIA relacionada aos IMS, sua fisiopatologia precisa é desconhecida, os sintomas relatados são inespecíficos e o tempo entre a exposição e o surgimento das manifestações é incerto. Por meio dessa revisão sistemática, conclui-se que, até o presente momento, não existem evidências científicas suficientes para estabelecer a causalidade do desenvolvimento da síndrome autoimune induzida por adjuvantes decorrente de implantes mamários de silicone.

Adjuvant-induced autoimmune syndrome (ASIA) and its diagnostic criteria were described by Shoenfeld in 2011, relating symptoms of autoimmunity to adjuvants, such as silicone, present in breast implants. This systematic review aimed to gather data from the literature on symptomatology, incidence and proposed treatments for ASIA caused by silicone breast implants (SBI). Searches were carried out in PubMed, LILACS, Embase and Cochrane databases, using the descriptors "Autoimmune Syndrome Induced by Adjuvants," "Breast implant," and "Silicone Implant Incompatibility Syndrome." The search strategy generated 95 articles, of which 20 were included in the review. The authors suggest three main theories to explain the development of the syndrome: genetic predisposition, silicone bleeding and the formation of a periprosthetic capsule. The most frequently described clinical manifestations include chronic fatigue, arthralgia, myalgia, and cognitive and sleep disorders. There is no consensus on laboratory findings and associated risk factors; recent studies propose expanding the diagnostic criteria initially described. Adequate treatment remains controversial, ranging from medications to prosthesis explantation. Although the reviewed articles suggest the existence of ASIA related to SBI, its precise pathophysiology is unknown, the symptoms reported are nonspecific, and the time between exposure and the onset of manifestations is uncertain. This systematic review concludes that, to date, there is not enough scientific evidence to establish the causality of the development of adjuvant-induced autoimmune syndrome resulting from silicone breast implants.

Motion Sensors for Knee Angle Recognition in Muscle Rehabilitation Solutions.

The progressive loss of functional capacity due to aging is a serious problem that can compromise human locomotion capacity, requiring the help of an assistant and reducing independence. The NanoStim project aims to develop a system capable of performing treatment with electrostimulation at the patient's home, reducing the number of consultations. The knee angle is one of the essential attributes in this context, helping understand the patient's movement during the treatment session. This article presents a wearable system that recognizes the knee angle through IMU sensors. The hardware chosen for the wearables are low cost, including an ESP32 microcontroller and an MPU-6050 sensor. However, this hardware impairs signal accuracy in the multitasking environment expected in rehabilitation treatment. Three optimization filters with algorithmic complexity O(1) were tested to improve the signal's noise. The complementary filter obtained the best result, presenting an average error of 0.6 degrees and an improvement of 77% in MSE. Furthermore, an interface in the mobile app was developed to respond immediately to the recognized movement. The systems were tested with volunteers in a real environment and could successfully measure the movement performed. In the future, it is planned to use the recognized angle with the electromyography sensor.

Uso do retalho tubular retroauricular para reconstrução da hélice e lóbulo da orelha / Use of retroauricular tubular flap for ear helix and ear lobe reconstruction

Defeitos de orelha são frequentes e de etiologias diversas. Ainda assim, a reconstrução de orelha permanece um desafio dentro da cirurgia plástica reconstrutiva, principalmente devido a anatomia e a escassez de tecido local. Embora pouco utilizado, o retalho tubular retroauricular se apresenta como alternativa para reconstrução da hélice e lóbulo. No presente estudo os autores descrevem a técnica operatória, bem como relatam um caso em que foi utilizado. Realizou-se uma avaliação do resultado operatório de quatro casos de reconstrução de orelha utilizando o retalho tubular retroauricular, através de questionários encaminhados para avaliadores leigos e cirurgiões plásticos. O resultado estético final foi classificado como bom ou excelente por 35% dos avaliadores leigos e 50% dos cirurgiões plásticos. Já o resultado operatório foi avaliado como bom ou excelente por 70% dos leigos e 80% dos cirurgiões plásticos. Os resultados permitem concluir que a técnica do retalho tubular retroauricular para reconstrução de defeitos da borda de hélice pode ser indicada, com resultados satisfatórios.

Ear defects are frequent and result of many etiologies, even though ear reconstruction remains a challenge in plastic reconstructive surgery due to anatomy and local tissue paucity. Despite being rarely used, the tubular retroauricular flap presents as an alternative for helix and lobule reconstruction. In this article, the authors describe the operative technique and report a case in which it was used. Also, plastic surgeons and laypeople rated the operative results of four cases of ear reconstructions using the tubular retroauricular flap. The final esthetic result was rated as good or excellent by 35% of laypeople and 50% of plastic surgeons, whereas the operative result was rated as good or excellent by 70% of laypeople and 80% of plastic surgeons. Thereby the findings and authors' experience, we can recommend the tubular retroauricular flap technique for reconstructing ear helix border defects.

The cholesteryl ester transfer protein (CETP) raises cholesterol levels in the brain.

The cholesteryl ester transfer protein (CETP) is a lipid transfer protein responsible for the exchange of cholesteryl esters and triglycerides between lipoproteins. Decreased CETP activity is associated with longevity, cardiovascular health, and maintenance of good cognitive performance. Interestingly, mice lack the CETP-encoding gene and have very low levels of LDL particles compared with humans. Currently, the molecular mechanisms induced because of CETP activity are not clear. To understand how CETP activity affects the brain, we utilized CETP transgenic (CETPtg) mice that show elevated LDL levels upon induction of CETP expression through a high-cholesterol diet. CETPtg mice on a high-cholesterol diet showed up to 22% higher cholesterol levels in the brain. Using a microarray on mostly astrocyte-derived mRNA, we found that this cholesterol increase is likely not because of elevated de novo synthesis of cholesterol. However, cholesterol efflux is decreased in CETPtg mice along with an upregulation of the complement factor C1Q, which plays a role in neuronal cholesterol clearance. Our data suggest that CETP activity affects brain health through modulating cholesterol distribution and clearance. Therefore, we propose that CETPtg mice constitute a valuable research tool to investigate the impact of cholesterol metabolism on brain function.

Focal Dermal Hypoplasia (Goltz Syndrome): A Case Report Showing a Wide Variety of Systemic and Oral Manifestations.

Focal dermal hypoplasia (FDH), also known as Goltz syndrome, consists of an unusual genodermatosis that affects tissues of ectodermal and mesodermal origin and various organs and systems, especially skin, bones, eyes, and oral cavity. While systemic manifestations of FDH have been well documented, the oral manifestations have not been extensively discussed. We present a 22-year-old female patient with history of FDH that showed a variety of systemic and oral manifestations. FDH was diagnosed at birth based on cutaneous alterations. Extra and intraoral examination showed facial asymmetry, lip and perioral atrophy, upper lip papilloma, malocclusion, enamel hypoplasia, and gingival hyperplasia. Mucosal lesions, periodontal diseases, and malocclusion were treated by oral surgery, periodontal therapy and orthodontic treatment, respectively. Although FDH is an uncommon syndrome, health professionals should be aware of its systemic and oral manifestations to establish an early diagnosis and adequate treatment.

Therapeutic effects of a lipid transfer protein isolated from Morinda citrifolia L. (noni) seeds on irinotecan-induced intestinal mucositis in mice.

This work aimed to evaluate the activity of a lipid transfer protein isolated from Morinda citrifolia L. seeds, McLTP1, on the development of intestinal mucositis following irinotecan administration. McLTP1 (0.5, 2, and 8 mg/kg, i.v.) was injected into mice 1h before irinotecan administration (75 mg/kg, i.p.; 4 days), and then for additional 6 days. Seven days after the first dose of irinotecan, diarrhea was assessed, and the intestine was removed for histological evaluation, assessment of intestinal over-contractility, measurement of myeloperoxidase (MPO), proinflammatory cytokines and chemokine (IL-1, IL-6, and KC levels - a murine homolog of human IL-8 chemokine), analysis of cyclooxygenase 2 (COX-2), nuclear factor kappa B (NF-κB), and nitric oxide synthase (iNOS) expression. At the two highest doses, McLTP1 administration decreased mortality and diarrhea. McLTP1 (8 mg/kg, i.v.) significantly prevented irinotecan-induced intestinal damage and led to a reduction in over-contractility of the intestinal muscle (p < 0.05). Moreover, McLTP1 decreased the MPO, IL-1ß, IL-6, and KC levels by 74.7%, 42%, 92.9%, and 95.9%, respectively. Also, the expression of COX-2, NF-κB, and iNOS was reduced. Our study provides a potential new therapeutic for preventing irinotecan-induced mucositis, improved clinical parameters, and reduced inflammation.

Correction: Netto et al. Hypovitaminosis D Is Associated with Higher Levels of Inflammatory Cytokines and with HAM/TSP in HTLV-Infected Patients. Viruses 2021, 13, 2223.

In the original publication [...].

The Succinate Receptor SUCNR1 Resides at the Endoplasmic Reticulum and Relocates to the Plasma Membrane in Hypoxic Conditions.

The GPCR SUCNR1/GPR91 exerts proangiogenesis upon stimulation with the Krebs cycle metabolite succinate. GPCR signaling depends on the surrounding environment and intracellular localization through location bias. Here, we show by microscopy and by cell fractionation that in neurons, SUCNR1 resides at the endoplasmic reticulum (ER), while being fully functional, as shown by calcium release and the induction of the expression of the proangiogenic gene for VEGFA. ER localization was found to depend upon N-glycosylation, particularly at position N8; the nonglycosylated mutant receptor localizes at the plasma membrane shuttled by RAB11. This SUCNR1 glycosylation is physiologically regulated, so that during hypoxic conditions, SUCNR1 is deglycosylated and relocates to the plasma membrane. Downstream signal transduction of SUCNR1 was found to activate the prostaglandin synthesis pathway through direct interaction with COX-2 at the ER; pharmacologic antagonism of the PGE2 EP4 receptor (localized at the nucleus) was found to prevent VEGFA expression. Concordantly, restoring the expression of SUCNR1 in the retina of SUCNR1-null mice renormalized vascularization; this effect is markedly diminished after transfection of the plasma membrane-localized SUCNR1 N8A mutant, emphasizing that ER localization of the succinate receptor is necessary for proper vascularization. These findings uncover an unprecedented physiologic process where GPCR resides at the ER for signaling function.

Successful Pre-Clinical Management of Irinotecan-Debilitated Animals: A Protein- Based Accessory Phytomedicine.

BACKGROUND: Calotropis procera is a laticiferous plant (Apocynaceae) found in tropical regions all over the world. The ultrastructural characteristics of laticifers, their restricted distribution among different taxonomic groups, and in some species in each clade, as peptidases from latex, make them very attractive for biological analysis. OBJECTIVE: The study aims to investigate the effects of LP-PII-IAA (laticifer protein (LP) sub-fraction II (PII) of C. procera presenting an iodoacetamide-inhibited cysteine proteinase activity) on irinotecan-induced intestinal mucositis, a serious adverse effect of this medicine for the treatment of cancer. METHODS: LP-PII-IAA is composed of closely related isoforms (90%) of peptidases derived from catalysis and an osmotin protein (5%). Animals receiving co-administration of LP-PII-IAA presented a significant decrease in mortality, absence of diarrhea, histological preservation, and normalization of intestinal functions. RESULTS: Clinical homeostasis was accompanied by a reduction in MPO activity and declined levels of IL-1ß, IL-6 and KC, while the IL-10 level increased in LP-PII-IAA-treated animals. COX-2 and NF-kB immunostaining was reduced and the levels of oxidative markers (GSH, MDA) were normalized in animals that received LP-PII-IAA. CONCLUSION: We suggest that peptidases from the latex of Calotropis procera were instrumental in the suppression of the adverse clinical and physiological effects of irinotecan.

Maxillary and Orbital Floor Reconstruction with Parallel Segments of the Fibula Free Flap: A Technical Note.

Introduction: The fibula free flap (FFF) is considered a gold standard for maxillary reconstructions, and in the last few decades, this flap has been widely used for mandibular defects, with a range of modifications, which have allowed the improvement and greater success. The reconstructions of the maxilla and midface are less reported than mandibular reconstructions, despite the remarkable evolution over the years. In the reconstruction of type IIIa maxillary defects using FFF, some authors report that it may not provide enough height to support the orbit in class 3 and 4 defects. Others also encountered several difficulties, mainly in modeling fibular bone (FB) for the zygomatic-maxilla complex reconstruction and orbital floor, due to the difficulty in rotating the soft tissues, pedicle, orientation of the (FB) segments. Objective: To show this new technique presents another option for maxillary reconstruction with a FFF in type IIIa defects. Methods: After harvesting FFF in the standard fashion, differentiated osteotomies, modeling, and arrangement of the fibular bone segments are performed. Results and Conclusion: This new technique presented has the advantage of requiring only one flap, promoting the resolution of the technical difficulties previously reported.

Microglia-mediated degradation of perineuronal nets promotes pain.

Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity.

mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation.

The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. Tissue inflammation, by changing the intrinsic properties of the nociceptive endings, leads to nociceptive hyperexcitability and thus to the development of inflammatory pain. Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain. Pharmacological activation of mTORC2 induced elongation and branching of nociceptor peripheral endings and caused long-lasting pain hypersensitivity. Conversely, nociceptor-specific deletion of the mTORC2 regulatory protein rapamycin-insensitive companion of mTOR (Rictor) prevented inflammation-induced elongation and branching of cutaneous nociceptive fibers and attenuated inflammatory pain hypersensitivity. Computational modeling demonstrated that mTORC2-mediated structural changes in the nociceptive terminal tree are sufficient to increase the excitability of nociceptors. Targeting mTORC2 using a single injection of antisense oligonucleotide against Rictor provided long-lasting alleviation of inflammatory pain hypersensitivity. Collectively, we showed that tissue inflammation-induced activation of mTORC2 causes structural plasticity of nociceptive free nerve endings in the epidermis and inflammatory hyperalgesia, representing a therapeutic target for inflammatory pain.