Muscle-Bone Crosstalk in the Masticatory System: From Biomechanical to Molecular Interactions.

The masticatory system is a complex and highly organized group of structures, including craniofacial bones (maxillae and mandible), muscles, teeth, joints, and neurovascular elements. While the musculoskeletal structures of the head and neck are known to have a different embryonic origin, morphology, biomechanical demands, and biochemical characteristics than the trunk and limbs, their particular molecular basis and cell biology have been much less explored. In the last decade, the concept of muscle-bone crosstalk has emerged, comprising both the loads generated during muscle contraction and a biochemical component through soluble molecules. Bone cells embedded in the mineralized tissue respond to the biomechanical input by releasing molecular factors that impact the homeostasis of the attaching skeletal muscle. In the same way, muscle-derived factors act as soluble signals that modulate the remodeling process of the underlying bones. This concept of muscle-bone crosstalk at a molecular level is particularly interesting in the mandible, due to its tight anatomical relationship with one of the biggest and strongest masticatory muscles, the masseter. However, despite the close physical and physiological interaction of both tissues for proper functioning, this topic has been poorly addressed. Here we present one of the most detailed reviews of the literature to date regarding the biomechanical and biochemical interaction between muscles and bones of the masticatory system, both during development and in physiological or pathological remodeling processes. Evidence related to how masticatory function shapes the craniofacial bones is discussed, and a proposal presented that the masticatory muscles and craniofacial bones serve as secretory tissues. We furthermore discuss our current findings of myokines-release from masseter muscle in physiological conditions, during functional adaptation or pathology, and their putative role as bone-modulators in the craniofacial system. Finally, we address the physiological implications of the crosstalk between muscles and bones in the masticatory system, analyzing pathologies or clinical procedures in which the alteration of one of them affects the homeostasis of the other. Unveiling the mechanisms of muscle-bone crosstalk in the masticatory system opens broad possibilities for understanding and treating temporomandibular disorders, which severely impair the quality of life, with a high cost for diagnosis and management.

Different Trypanosoma cruzi calreticulin domains mediate migration and proliferation of fibroblasts in vitro and skin wound healing in vivo.

Calreticulin is an endoplasmic reticulum-resident, calcium-binding, stress-produced, chaperone protein that serves multiple functions and is widely distributed in eukaryotic cells. Exogenously applied recombinant calreticulin solution, markedly enhanced the rate and quality of skin wound healing. These modulatory effects are more efficient than commercially available topic platelet-derived growth factor ointments (Regranex®). Trypanosoma cruzi calreticulin is more effective in equimolar terms to human counterpart in accelerating skin wound healing. While the effect of externally added recombinant parasite calreticulin on wound healing has been reported, the domains responsible for these modulatory effects have not yet been established. Here, recombinant parasite calreticulin and some of its domains were tested to assess their influence in increasing proliferation and migration of fibroblasts in vitro and rat skin wound healing in vivo. Herein, we propose that Trypanosoma cruzi whole calreticulin or some of its domains are differentially involved in the modulation of wound-healing cell migration and proliferation, and cosmetic outcome. Therefore, precise combination of the parasite protein and its domains could allow us to tailor-specific desired effects during the skin wound-healing process.

Early molecular response and microanatomical changes in the masseter muscle and mandibular head after botulinum toxin intervention in adult mice.

BACKGROUND: Masseter muscle paralysis induced by botulinum toxin type A (BoNTA) evokes subchondral bone loss in mandibular heads of adult rats and growing mice after 4 weeks. However, the primary cellular and molecular events leading to altered bone remodeling remain unexplored. Thus, the aim of the current work has been to assess the molecular response that precedes the early microanatomical changes in the masseter muscle and subchondral bone of the mandibular head in adult mice after BoNTA intervention. METHODS: A pre-clinical in vivo study was performed by a single intramuscular injection of 0.2 U BoNTA in the right masseter (experimental) of adult BALB/c mice. The contralateral masseter was injected with vehicle (control). Changes in mRNA levels of molecular markers of bone loss or muscle atrophy/regeneration were addressed by qPCR at day 2 or 7, respectively. mRNA levels of receptor activator of nuclear factor-κB ligand (RANKL) was assessed in mandibular heads, whilst mRNA levels of Atrogin-1/MAFbx, MuRF-1 and Myogenin were addressed in masseter muscles. In order to identify the early microanatomical changes at day 14, fiber diameters in transversal sections of masseter muscles were quantified, and histomorphometric analysis was used to determine the bone per tissue area and the trabecular thickness of subchondral bone of the mandibular heads. RESULTS: An increase of up to 4-fold in RANKL mRNA levels were detected in mandibular heads of the BoNTA-injected sides as early as 2 days after intervention. Moreover, a 4-6 fold increase in Atrogin-1/MAFbx and MuRF-1 and an up to 25 fold increase in Myogenin mRNA level were detected in masseter muscles 7 days after BoNTA injections. Masseter muscle mass, as well as individual muscle fiber diameter, were significantly reduced in BoNTA-injected side after 14 days post-intervention. At the same time, in the mandibular heads from the treated side, the subchondral bone loss was evinced by a significant reduction in bone per tissue area (-40%) and trabecular thickness (-55%). CONCLUSIONS: Our results show that masseter muscle paralysis induced by BoNTA leads to significant microanatomical changes by day 14, preceded by molecular changes as early as 2 days in bone, and 7 days in muscle. Therefore, masseter muscle atrophy and subchondral bone loss detected at 14 days are preceded by molecular responses that occur during the first week after BoNTA intervention.

[Postoperative analgesia for orthopedic surgeries of the hip and femur: a comparison between psoas compartment and inguinal paravascular blocks.]. / Analgesia pós-operatória para procedimentos cirúrgicos ortopédicos de quadril e fêmur: comparação entre bloqueio do compartimento do psoas e bloqueio perivascular inguinal.

BACKGROUND AND OBJECTIVES: This study evaluated the efficacy of a single injection of 0.25% bupivacaine in the psoas compartment or inguinal paravascular for postoperative analgesia in patients undergoing orthopedic surgeries using a peripheral nerve stimulator. METHODS: One hundred patients who had a lumbar plexus block through the psoas compartment were compared to 100 patients who had an inguinal paravascular block, using a peripheral nerve stimulator, with 40 mL of 0.25% bupivacaine. The analgesia of the ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral, and obturator nerves was assessed 4, 8, 12, 16, 20, and 24 hours after the end of the surgical procedure. Pain severity was also evaluated in the same period. The amount of opioids administered in the postoperative period was recorded. A radiological study with non-ionic contrast was done in five patients in each group to evaluate the dispersion of the anesthetic. RESULTS: The ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral, and obturator nerves were blocked in 92% of the patients with psoas compartment block versus 62% in those with inguinal paravascular block. Lumbar plexus block reduced the need for opioids, and 42% of the patients who underwent psoas compartment block and 36% of the patients who underwent inguinal paravascular block did not need additional analgesics in the postoperative period. Analgesia lasted for approximately 21 hours in the psoas compartment block and 15 hours in the inguinal paravascular block. CONCLUSIONS: Psoas compartment block and inguinal paravascular block are excellent techniques for postoperative analgesia in orthopedic surgeries, decreasing the need for opioids. This study showed that the injection in the psoas compartment was easier and more effective in blocking the five nerves of the lumbar plexus.

Bilateral pudendal nerves block for postoperative analgesia with 0.25% S75:R25 bupivacaine. Pilot study on outpatient hemorrhoidectomy.

BACKGROUND AND OBJECTIVES: Hemorrhoidectomy may be performed under several anesthetic techniques and in outpatient regimen. Postoperative pain is severe and may delay discharge. This study aimed at evaluating bilateral pundendal nerves block for post- hemorrhoidectomy analgesia. METHODS: Bilateral pundendal nerves block with 0.25% S75:R25 bupivacaine was performed with nerve stimulator in 35 patients submitted to hemorrhoidectomy under spinal anesthesia. Evaluated parameters were pain severity, duration of analgesia, demand analgesia and possible technique-related complications. Data were evaluated 6, 12, 18, 24 and 30 hours after surgery completion. RESULTS: Successful pudendal nerves stimulation was achieved in all patients. There has been no severe pain in all evaluated moments. At 12 hours after blockade, all patients had perineal anesthesia; at 18 hours, 17 patients and at 24 hours, 10 patients still presented perineal anesthesia. Postoperative analgesia was optimal for 18 patients; satisfactory, for 5 patients; and unsatisfactory, for 7 patients. Mean analgesic duration was 23.77 hours. There were no changes in blood pressure, heart rate, no nausea and vomiting were observed. All patients had spontaneous micturition. No local anesthetic-related local or systemic complications were observed. Technique was considered excellent by 27 patients and only 3 male patients considered it satisfactory due to penile anesthesia. CONCLUSIONS: Bilateral pudendal nerves block oriented by nerve stimulator provides excellent analgesia with low need for opioids, without local or systemic complications and without urinary retention. Controlled studies might be able to show whether this should be the first analgesic option for hemorrhoidectomies. Perineal anesthesia lasting 20.21 hours shall induce further studies with stimulator-oriented pudendal block.

Analgesia pós-operatória para procedimentos cirúrgicos ortopédicos de quadril e fêmur: comparação entre bloqueio do compartimento do psoas e bloqueio perivascular inguinal / Postoperative analgesia for orthopedic surgeries of the hip and femur: a comparison between psoas compartment and inguinal paravascular blocks

JUSTIFICATIVA E OBJETIVOS: Este estudo avaliou a eficácia da injeção única de bupivacaína a 0,25 por cento no compartimento do psoas ou perivascular inguinal por meio do estimulador de nervos periféricos para analgesia pós-operatória em pacientes submetidos a intervenções cirúrgicas ortopédicas. MÉTODO: Cem pacientes receberam bloqueio do plexo lombar através do compartimento do psoas e foram comparados com 100 pacientes que receberam bloqueio do plexo lombar via perivascular inguinal, identificados pelo estimulador de nervos periféricos com a injeção de 40 mL bupivacaína a 0,25 por cento sem epinefrina. A analgesia nos nervos ilioinguinal, genitofemoral, cutâneo femoral lateral, femoral e obturatório foi avaliada 4, 8, 12, 16, 20 e 24 horas após o final da intervenção cirúrgica. A intensidade da dor foi também avaliada no mesmo período. A quantidade de opióides administrada no pós-operatório foi anotada. Em cinco pacientes de cada grupo, estudo radiográfico com contraste não-iônico foi realizado para avaliar a dispersão da solução anestésica. RESULTADOS: Os nervos ilioinguinal, genitofemoral, cutâneo femoral lateral, femoral e obturatório foram bloqueados em 92 por cento dos pacientes no compartimento do psoas versus 62 por cento no bloqueio perivascular inguinal. O bloqueio do plexo lombar reduziu a necessidade de opióides e 42 por cento dos pacientes submetidos ao bloqueio do compartimento do psoas e 36 por cento dos pacientes no bloqueio inguinal não necessitaram de analgésico adicional no pós-operatório. A duração da analgesia foi em torno de 21 horas com bloqueio do compartimento do psoas e 15 horas com bloqueio perivascular inguinal. CONCLUSÕES: O bloqueio do compartimento do psoas e perivascular inguinal é uma excelente técnica para analgesia pós-operatória em intervenções cirúrgicas ortopédicas reduzindo a necessidade de opióides. Este estudo mostrou que a injeção no compartimento do psoas foi mais fácil e mais efetiva no bloqueio...

BACKGROUND AND OBJECTIVES: This study evaluated the efficacy of a single injection of 0.25 percent bupivacaine in the psoas compartment or inguinal paravascular for postoperative analgesia in patients undergoing orthopedic surgeries using a peripheral nerve stimulator. METHODS: One hundred patients who had a lumbar plexus block through the psoas compartment were compared to 100 patients who had an inguinal paravascular block, using a peripheral nerve stimulator, with 40 mL of 0.25 percent bupivacaine. The analgesia of the ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral, and obturator nerves was assessed 4, 8, 12, 16, 20, and 24 hours after the end of the surgical procedure. Pain severity was also evaluated in the same period. The amount of opioids administered in the postoperative period was recorded. A radiological study with non-ionic contrast was done in five patients in each group to evaluate the dispersion of the anesthetic. RESULTS: The ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral, and obturator nerves were blocked in 92 percent of the patients with psoas compartment block versus 62 percent in those with inguinal paravascular block. Lumbar plexus block reduced the need for opioids, and 42 percent of the patients who underwent psoas compartment block and 36 percent of the patients who underwent inguinal paravascular block did not need additional analgesics in the postoperative period. Analgesia lasted for approximately 21 hours in the psoas compartment block and 15 hours in the inguinal paravascular block. CONCLUSIONS: Psoas compartment block and inguinal paravascular block are excellent techniques for postoperative analgesia in orthopedic surgeries, decreasing the need for opioids. This study showed that the injection in the psoas compartment was easier and more effective in blocking the five nerves of the lumbar plexus.

JUSTIFICATIVA Y OBJETIVOS: Este estudio evaluó la eficacia de la inyección única de bupivacaína a 0,25 por ciento en el compartimiento del psoas o perivascular inguinal a través del estimulador de nervios periféricos para analgesia postoperatoria en pacientes sometidos a intervenciones quirúrgicas ortopédicas. MÉTODO: Cien pacientes recibieron bloqueo del plexo lumbar a través del compartimiento del psoas y fueron comparados con 100 pacientes que recibieron bloqueo del plexo lumbar vía perivascular inguinal, identificados por el estimulador de nervios periféricos con la inyección de 40 mL bupivacaína a 0,25 por ciento sin epinefrina. La analgesia en los nervios ilioinguinal, genitofemoral, cutáneo femoral lateral, femoral y obturatorio fue evaluada a las 4, 8, 12, 16, 20 y 24 horas después del final de la intervención quirúrgica. La intensidad del dolor también fue medida en el mismo período. La cantidad de opioides administrada en el postoperatorio fue anotada. En cinco pacientes de cada grupo, un estudio radiográfico con contraste no iónico se realizó para medir la dispersión de la solución anestésica. RESULTADOS: Los nervios ilioinguinal, genitofemoral, cutáneo femoral lateral, femoral y obturatorio fueron bloqueados en 92 por ciento de los pacientes en el compartimiento del psoas versus 62 por ciento en el bloqueo perivascular inguinal. El bloqueo del plexo lumbar redujo la necesidad de opioides y 42 por ciento de los pacientes sometidos al bloqueo del compartimiento del psoas y 36 por ciento de los pacientes en el bloqueo inguinal no necesitaron analgésico adicional en el postoperatorio. La duración de la analgesia fue de aproximadamente 21 horas con el bloqueo del compartimiento del psoas y 15 horas en el bloqueo perivascular inguinal. CONCLUSIONES: El bloqueo del compartimiento del psoas y perivascular inguinal es una excelente técnica para la analgesia postoperatoria en intervenciones quirúrgicas ortopédicas reduciendo la necesidad...

Analgesia pós-operatória com bloqueio bilateral do nervo pudendo com bupivacaína S75:R25 a 0, 25 por cento: estudo piloto em hemorroidectomia sob regime ambulatorial / Postoperative analgesia with bilateral pudendal nerve block with bupivacaine S75:R25 at 0.25%: pilot study in hemorrhoidectomy on an outpatient basis

JUSTIFICATIVA E OBJETIVOS: A hemorroidectomia pode ser realizada sob várias técnicas anestésicas e em regime ambulatorial. A dor pós-operatória é intensa e pode atrasar o retorno para a residência. O objetivo deste estudo foi avaliar as vantagens e a realização do bloqueio bilateral dos nervos pudendos para analgesia pós-operatória em hemorroidectomias. MÉTODO: O bloqueio bilateral dos nervos pudendos com bupivacaína S75:R25 a 0,25 por cento foi realizado com estimulador de nervos em 35 pacientes submetidos à hemorroidectomia sob raquianestesia. Foram avaliadas intensidade da dor, duração da analgesia, analgesia de demanda e eventuais complicações relacionadas à técnica. Os dados foram avaliados às 6, 12, 18, 24 e 30 horas após o término da intervenção cirúrgica. RESULTADOS: Em todos os pacientes, foi obtido sucesso com a estimulação de ambos os nervos pudendos. Em nenhum momento da avaliação ocorreu dor intensa. Até 12 horas após o bloqueio, todos os pacientes apresentaram anestesia na região perineal; com 18 horas, 17 pacientes e 24 horas; 10 pacientes A analgesia pós-operatória foi ótima em 18 pacientes; satisfatória, em cinco pacientes; e insatisfatória, em sete pacientes. A duração média da analgesia foi de 23,77 horas. Não ocorreram alterações da pressão arterial, da freqüência cardíaca, nem foram observadas náuseas ou vômitos. Todos os pacientes tiveram micção espontânea. Nenhuma complicação local ou sistêmica foi relacionada ao anestésico local. Vinte e sete pacientes classificaram de excelente a técnica de analgesia e apenas três pacientes do sexo masculino ficaram satisfeitos o que foi justificado pela anestesia no pênis. CONCLUSÕES: O bloqueio bilateral dos nervos pudendos, orientado por estimulador de nervos, proporciona a analgesia de excelente qualidade, com baixa necessidade de opióides, sem complicações local ou sistêmica e sem retenção urinária. Estudos controlados permitirão demonstrar se esta técnica deve ser a primeira opção para analgesia em hemorroidectomias. A permanência de anestesia perineal por 20,21 horas deverá induzir novos trabalhos com o bloqueio dos nervos pudendos orientado por estimulador para o ato cirúrgico.