RESUMO
Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective ß2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a ß2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed.
Assuntos
Clembuterol , Modelos Animais de Doenças , Fibromialgia , Hiperalgesia , Atrofia Muscular , Sistema Nervoso Simpático , Animais , Feminino , Fibromialgia/patologia , Fibromialgia/fisiopatologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Hiperalgesia/fisiopatologia , Hiperalgesia/patologia , Sistema Nervoso Simpático/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/patologia , Clembuterol/farmacologia , Ratos , Carragenina/toxicidade , Ratos Sprague-Dawley , Dor/patologia , Dor/fisiopatologia , Epinefrina , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Catecolaminas/metabolismo , Agonistas Adrenérgicos beta/farmacologiaRESUMO
OBJECTIVE: To report the effects of a tunica vagina flap on testicular compartment syndrome. METHODS: This single-arm clinical trial was conducted from September 2020 to October 2021. Consecutive patients with suspected testicular torsion within 24 hours of pain onset were included. Patients with past testicular torsion, bilateral torsion, or previous atrophy were excluded. The tunica vaginalis was opened, and the intratesticular pressure was measured before testicular retrieval from the scrotum and detorsion (P1), after detorsion (P2), and after transverse incision (P3). A tunica vaginalis flap was performed and a new intratesticular pressure was recorded (P4). The contralateral testicular pressure was recorded before fixation (Pc). The minimum follow-up period was 6 months. RESULTS: Fifteen patients were recruited from September 2020 to October 2021. Nine patients completed the follow-up. The median age (range) was 15 years (9-19). The mean P1, P2, P3, P4, and Pc (range) were 43, 60, 23, 20, and 14mmHg, respectively. The atrophy rate was 66.3% and the viability was 88.9%. No major complications were observed. CONCLUSION: The modified tunica vaginalis flap in acute testicular torsion decreased intratesticular pressure. Furthermore, normal testicular pressure can improve testicular preservation. It can also decrease testicular pressure to normal levels and preserve the testicular parenchyma. Testicular torsion causes orchiectomy in more than 80% of the cases after 24 hours of pain onset. Testicular detorsion only (P1-P2) showed a small difference in intratesticular pressure (median 4mmHg). Testicular incision (P2-P3) only demonstrated a major pressure decrease (median, 45mmHg). The final pressure after TVR was similar to the non-twisted testicle pressure (median, 1mmHg). Testicular salvage (88.9%) and atrophy (66.3%) rates were slightly higher than the previous literature reports, perhaps the initial learning curve of this novel technique.
Assuntos
Torção do Cordão Espermático , Testículo , Adolescente , Humanos , Masculino , Atrofia/complicações , Atrofia/patologia , Descompressão , Dor/complicações , Dor/patologia , Torção do Cordão Espermático/cirurgia , Testículo/cirurgiaRESUMO
Las urgencias odontológicas son, quizá, las razones principales de atención en el consultorio, muchas veces el significado de dolor se encuentra acompañado por inflamación; el uso de antiinflamatorios no esteroideos (AINES) es común en el ejercicio de la odontología por la excelente respuesta analgésica y antiinflamatoria que tiene, por lo que es importante conocer la fisiopatología de la inflamación y el dolor y cómo actúan los AINES, ya que algunos de estos fármacos tienen respuestas adversas y sitios de acción importantes. Los factores de riesgo por inflamación y dolor nos obligan a conocer la variedad de fármacos que no entran en la clasificación de AINES y que tenemos a disposición, hay más opciones para la elección ante la presencia de inflamación por un factor en particular, cada uno de éstos tienen indicaciones y contraindicaciones que conoceremos, lo cual nos ampliará el conocimiento para dar una prescripción ante la presencia de eventos inflamatorios. Se realizó un estudio detallado de artículos bibliográficos de cada tema, los fármacos más usados en odontología son los AINES, hay poco uso y conocimiento de antiinflamatorios que podemos usar en urgencias, el porcentaje de uso de los AINES derivados del ácido propiónico es alto por la excelente respuesta en pacientes y otras veces por el desconocimiento de más opciones (AU)
Dental emergencies are perhaps the main reasons for care in the office, many times the meaning of pain is accompanied by inflammation, the use of non-steroidal anti-inflammatory drugs is common in the practice of dentistry due to the excellent analgesic and anti-inflammatory response it has, important is knowing the pathophysiology of inflammation and pain, how NSAIDs act, some of these drugs have adverse responses and important sites of action, risk factors for inflammation and pain require us to know the variety of drugs that do not enter the classification of NSAIDs and we have at our disposal, there are more options for choosing in the presence of inflammation due to a particular factor, each of these have indications and contraindications that we will know, it expands our knowledge to give a prescription in the presence of inflammatory events. A detailed study of bibliographic articles on each topic was carried out, the drugs most used in dentistry are NSAIDs, there is little use and knowledge of anti-inflammatories that we can use in the emergency room, the percentage of use of NSAIDs derived from propionic acid is high, due to the excellent response in patients and others due to lack of knowledge of more options (AU)
Assuntos
Humanos , Masculino , Feminino , Odontalgia , Preparações Farmacêuticas , Anti-Inflamatórios não Esteroides , Inflamação , Dor/patologia , Dor Pós-Operatória , Propionatos , Prostaglandinas/fisiologia , Interações Medicamentosas , Ciclo-Oxigenase 1/farmacologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , EntorpecentesRESUMO
We have read the study by Siracusa et al. [...].
Assuntos
Fibromialgia/diagnóstico , Fibromialgia/patologia , Humanos , Hiperalgesia/patologia , Nociceptividade/fisiologia , Dor/patologiaRESUMO
The mechanistic interactions among redox status of leukocytes, muscle, and exercise in pain regulation are still poorly understood and limit targeted treatment. Exercise benefits are numerous, including the treatment of chronic pain. However, unaccustomed exercise may be reported as undesirable as it may contribute to pain. The aim of the present review is to evaluate the relationship between oxidative metabolism and acute exercise-induced pain, and as to whether improved antioxidant capacity underpins the analgesic effects of regular exercise. Preclinical and clinical studies addressing relevant topics on mechanisms by which exercise modulates the nociceptive activity and how redox status can outline pain and analgesia are discussed, in sense of translating into refined outcomes. Emerging evidence points to the role of oxidative stress-induced signaling in sensitizing nociceptor sensory neurons. In response to acute exercise, there is an increase in oxidative metabolism, and consequently, pain. Instead, regular exercise can modulate redox status in favor of antioxidant capacity and repair mechanisms, which have consequently increased resistance to oxidative stress, damage, and pain. Data indicate that acute sessions of unaccustomed prolonged and/or intense exercise increase oxidative metabolism and regulate exercise-induced pain in the post-exercise recovery period. Further, evidence demonstrates regular exercise improves antioxidant status, indicating its therapeutic utility for chronic pain disorders. An improved comprehension of the role of redox status in exercise can provide helpful insights into immune-muscle communication during pain modulatory effects of exercise and support new therapeutic efforts and rationale for the promotion of exercise.
Assuntos
Analgesia/efeitos adversos , Exercício Físico , Músculo Esquelético/patologia , Nociceptores/patologia , Estresse Oxidativo , Dor/patologia , Células Receptoras Sensoriais/patologia , Humanos , Músculo Esquelético/metabolismo , Nociceptores/imunologia , Nociceptores/metabolismo , Oxirredução , Dor/etiologia , Dor/metabolismo , Células Receptoras Sensoriais/imunologia , Células Receptoras Sensoriais/metabolismoRESUMO
OBJECTIVE: This split-mouth randomized controlled clinical trial assessed the effect of 10% strontium chloride in combination with photobiomodulation (PBM) for the control of tooth sensitivity (TS) post-bleaching. METHODS: The upper/lower, right and left quadrants of fifty volunteers were randomized and allocated to four groups (n = 25): PLACEBO-placebo gel + simulation of PBM; Placebo + PBM; STRONTIUM-10% strontium chloride + simulation of PBM; and PBM + STRONTIUM-10% strontium chloride + PBM. All groups received tooth bleaching treatment with 35% hydrogen peroxide. For the PBM treatment, the laser tip was positioned in the apical and cervical regions of the teeth bleached in the respective hemi-arch. The laser system was operated in continuous mode, using 1.7 J of energy. A dose of 60 J/cm2 was applied to each point for 16 seconds under 808 nm near-infrared light (100mW of power), with a point area of 0.028 cm2. TS was assessed during a 21-day follow-up, using the modified visual analogue scale. RESULTS: In the intragroup assessment, the Friedman test indicated that PBM + STRONTIUM promoted the greatest reduction in TS after the second week of treatment (p ≤ 0.05). The Wilcoxon-Mann-Whitney test indicated that the groups Placebo + PBM, STRONTIUM, and STRONTIUM + PBM did not differ statistically (p ≥ 0.05) in the first and third weeks of treatment The group PLACEBO exhibited the greatest TS in the first three days after each bleaching session. CONCLUSION: The combination of 10% strontium chloride with PBM was effective in reducing post-bleaching TS; however, the combination of 10% strontium chloride with PBM was effective in reducing post-bleaching TS; however, it did not differ from the individual use of Placebo + PBM or STRONTIUM groups assessed after 21 days of follow-up.
Assuntos
Sensibilidade da Dentina/tratamento farmacológico , Terapia com Luz de Baixa Intensidade , Dor/tratamento farmacológico , Estrôncio/administração & dosagem , Adulto , Brasil/epidemiologia , Dentina/efeitos dos fármacos , Sensibilidade da Dentina/patologia , Feminino , Humanos , Lasers , Masculino , Dor/patologia , Placebos , Dente/efeitos dos fármacos , Dente/patologia , Clareamento Dental/normas , Adulto JovemRESUMO
This study investigated the effects of the protein-free galactomannan obtained from Delonix regia seeds (GM-DR) in an experimental osteoarthritis (OA) model. GM-DR was obtained from water-homogenized endosperms by collection of the supernatant and precipitation with ethanol. The remaining proteins in the galactomannan were removed by alkaline hydrolysis. Weight average molar mass (Mw) of the galactomannan was estimated in 5.8 × 105 g mol-1, presenting mannose:galactose ratio of 2.39:1. Rats received sodium monoiodoacetate (OA groups, 1 mg/25 µL) or saline (sham group) in the right tibio-tarsal joint. GM-DR (30-300 µg) was administered by intra-articular route at days 14 and 21 after OA induction. Hypernociception was evaluated daily by the measurement of the mechanical threshold required to cause joint flexion and paw withdrawal reflex. The 56-day animal groups were euthanized for joint histopahological analysis using the OARSI score system. Lower doses of GM-DR (30 and 100 µg) promoted antinociception from day 15 until the endpoint at day 56. Joint damage was reduced by GM-DR administration (100 µg) in OA-subjected animals, compared to the vehicle-treated OA group (5.9 ± 1.8 vs 19.0 ± 1.8, respectively, p < 0.05). Conclusion: Both antinociception and damage reduction suggest that Delonix regia galactomannan is a promising approach for osteoarthritis therapy.
Assuntos
Analgésicos/uso terapêutico , Mananas/uso terapêutico , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Modelos Animais de Doenças , Fabaceae , Articulações do Pé/efeitos dos fármacos , Articulações do Pé/patologia , Galactose/análogos & derivados , Ácido Iodoacético , Masculino , Nociceptividade/efeitos dos fármacos , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Dor/induzido quimicamente , Dor/patologia , Ratos Wistar , SementesRESUMO
BACKGROUND: Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). CASE PRESENTATION: Here, we present clinical and molecular findings in a 9-year-old girl with CIPA. The high-altitude indigenous Ecuadorian patient presented several health problems such as anhidrosis, bone fractures, self-mutilation, osteochondroma, intellectual disability and Riga-Fede disease. After the mutational analysis of NTRK1, the patient showed a clearly autosomal recessive inheritance pattern with the pathogenic mutation rs763758904 (Arg602*) and the second missense mutation rs80356677 (Asp674Tyr). Additionally, the genomic analysis showed 69 pathogenic and/or likely pathogenic variants in 46 genes possibly related to phenotypic heterogeneity, including the rs324420 variant in the FAAH gene. The gene ontology enrichment analysis showed 28 mutated genes involved in several biological processes. As a novel contribution, the protein-protein interaction network analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix involved in the response to stimulus and nervous system development. CONCLUSIONS: This is the first study that associates clinical, genomics and networking analyses in a Native American patient with consanguinity background in order to better understand CIPA pathogenesis.
Assuntos
Altitude , Marcadores Genéticos , Hipo-Hidrose/patologia , Mutação , Insensibilidade Congênita à Dor/patologia , Dor/patologia , Criança , Análise Mutacional de DNA , Feminino , Genômica , Humanos , Hipo-Hidrose/genética , Hipo-Hidrose/metabolismo , Dor/genética , Dor/metabolismo , Insensibilidade Congênita à Dor/genética , Insensibilidade Congênita à Dor/metabolismo , Mapas de Interação de ProteínasRESUMO
BACKGROUND: Ultraviolet B (UVB) radiation exposure promotes sunburn and thereby acute and chronic inflammatory processes, contributing to pain development and maintenance. New therapeutic alternatives are necessary because typical treatments can cause adverse effects. An attractive alternative would be to target the transient receptor potential ankyrin 1 (TRPA1), a calcium-permeable, non-selective cation channel, which is involved in a variety of inflammatory pain models. OBJECTIVE: Evaluate the peripheral participation of TRPA1 using a topical treatment (HC030031 gel formulation; a selective TRPA1 antagonist) in nociception and inflammation caused by a UVB radiation-induced burn model in male mice (25-30 g). METHODS: The mice were anaesthetised, and just the right hind paw was exposed to UVB radiation (0.75 J/cm2). Topical treatments were applied immediately after irradiation and once a day for 8 days. RESULTS: HC030031 gel presented suitable pH and spreadability factor, ensuring its quality and the therapeutic effect. HC030031 0.05 % reversed UVB-induced mechanical and cold allodynia, with maximum inhibition (Imax) of 69 ± 13 % and 100 % (on day 4), respectively. HC030031 0.05 % also reduced the paw edema and MPO activity, with Imax of 77 ± 6 % (on day 5) and 69 ± 28 %, respectively. Likewise, UVB radiation increased the H2O2 levels (a TRPA1 agonist) and the Ca2+ influx in mice spinal cord synaptosomes. UVB radiation-induced Ca2+ influx was reduced by HC030031. CONCLUSION: These findings confirm the activation of the TRPA1 channel by UVB radiation, suggesting that topical TRPA1 antagonists can be a new strategy for the adjuvant treatment of sunburn-associated pain and inflammation.
Assuntos
Acetanilidas/administração & dosagem , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Purinas/administração & dosagem , Queimadura Solar/tratamento farmacológico , Canal de Cátion TRPA1/antagonistas & inibidores , Administração Cutânea , Animais , Cálcio/metabolismo , Modelos Animais de Doenças , Humanos , Peróxido de Hidrogênio/metabolismo , Inflamação/etiologia , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Dor/etiologia , Dor/patologia , Pele/imunologia , Pele/patologia , Pele/efeitos da radiação , Medula Espinal/citologia , Medula Espinal/patologia , Queimadura Solar/etiologia , Queimadura Solar/patologia , Sinaptossomos/metabolismo , Canal de Cátion TRPA1/metabolismo , Raios Ultravioleta/efeitos adversosRESUMO
Clindamycin, a bacteriostatic semisynthetic lincosamide, is useful in the management of infections caused by aerobic and anaerobic Gram-positive cocci, including bacteremic pneumonia, streptococcal toxic shock syndrome and sepsis. It has been recently demonstrated that clindamycin inhibits in vitro and in vivo inflammatory cytokine production. In the present study, we investigated the effects of clindamycin in acute and chronic models of pain and inflammation in mice and the underlying mechanisms. Intraperitoneal (i.p.) administration of clindamycin (400 mg/kg) increased the animal's latency to exhibit the nociceptive behavior induced by noxious heat (hot plate model). Intrathecal injection of clindamycin (2, 10 and 50 µg) also increased the animals' latency to exhibit the nociceptive behavior. Tactile hypersensitivity and paw edema induced by intraplantar (i.pl.) injection of carrageenan were attenuated by previous administration of clindamycin (200 and 400 mg/kg, i.p.). Clindamycin (100, 200 and 400 mg/kg, i.p.) also attenuated ongoing tactile hypersensitivity and paw edema induced by i.pl. injection of complete Freund's adjuvant (CFA). The antinociceptive activity of clindamycin (400 mg/kg, i.p.) in the hot plate model was attenuated by previous administration of naltrexone (5 and 10 mg/kg, i.p.), but not glibenclamide or AM251. CFA-induced production of TNF-α and CXCL-1 was reduced by clindamycin (400 mg/kg, i.p.). Concluding, clindamycin exhibits activities in acute and chronic models of pain and inflammation. These effects are associated with reduced production of TNF-α and CXCL-1 and activation of opioidergic mechanisms. Altogether, these results indicate that the clindamycin's immunomodulatory effects may contribute to a pharmacological potential beyond its antibiotic property.