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S100 proteins comprise a family of structurally related proteins that are calcium-sensitive. S100 proteins have been found to play various roles in regulation of cell apoptosis, cell proliferation and differentiation, cell migration and invasion, energy metabolism, calcium homeostasis, protein phosphorylation, anti-microbial activity and inflammation in a variety of cell types. While the specific function of many S100 proteins remains unknown, some of the S100 proteins serve as disease biomarkers as well as possible therapeutic targets in skin diseases. Interface dermatitis (ID) is a histopathological term that covers many different skin conditions including cutaneous lupus erythematosus, lichen planus, and dermatomyositis. These pathologies share similar histological features, which include basal cell vacuolization and lymphocytic infiltration at the dermal-epidermal junction. In this review, we summarize how the S100 protein family contributes to both homeostatic and inflammatory processes in the skin. We also highlight the role of S100 proteins in neuronal signalling, describing how this might contribute to neuroimmune interactions in ID and other skin pathologies. Last, we discuss what is known about the S100 family proteins as both biomarkers and potential treatment targets in specific pathologies.
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Homeostasis , Proteínas S100 , Piel , Humanos , Proteínas S100/metabolismo , Piel/metabolismo , Piel/patología , Dermatitis/metabolismo , Enfermedades de la Piel/metabolismo , Biomarcadores/metabolismo , AnimalesRESUMEN
Chemokines play critical roles in the recruitment and activation of immune cells in both homeostatic and pathologic conditions. Here, we examined chemokine ligand-receptor pairs to better understand the immunopathogenesis of cutaneous lupus erythematosus (CLE), a complex autoimmune connective tissue disorder. We used suction blister biopsies to measure cellular infiltrates with spectral flow cytometry in the interface dermatitis reaction, as well as 184 protein analytes in interstitial skin fluid using Olink targeted proteomics. Flow and Olink data concordantly demonstrated significant increases in T cells and antigen presenting cells (APCs). We also performed spatial transcriptomics and spatial proteomics of punch biopsies using digital spatial profiling (DSP) technology on CLE skin and healthy margin controls to examine discreet locations within the tissue. Spatial and Olink data confirmed elevation of interferon (IFN) and IFN-inducible CXCR3 chemokine ligands. Comparing involved versus uninvolved keratinocytes in CLE samples revealed upregulation of essential inflammatory response genes in areas near interface dermatitis, including AIM2. Our Olink data confirmed upregulation of Caspase 8, IL-18 which is the final product of AIM2 activation, and induced chemokines including CCL8 and CXCL6 in CLE lesional samples. Chemotaxis assays using PBMCs from healthy and CLE donors revealed that T cells are equally poised to respond to CXCR3 ligands, whereas CD14+CD16+ APC populations are more sensitive to CXCL6 via CXCR1 and CD14+ are more sensitive to CCL8 via CCR2. Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6/CXCR1 and CCL8/CCR2, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3.
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INTRODUCTION: We conducted a single-blind, prospective, randomized, 3-arm controlled trial to compare the efficacy of interactive and noninteractive video-based with instructor-led teaching in acquiring and retaining basic surgical skills. METHODS: Participants were pretested after providing written instruction using a simulator. After the pretest, students were randomized to three groups: noninteractive video-based instruction (NIVBI), instructor-led teaching with concurrent feedback, and interactive video-based instruction (IVBI). An immediate post-test and a retention test were performed 1 mo after the practice session's end to assess the efficacy of practice conditions. Two experts blinded to the experimental condition evaluated performance using expert-based assessment. Data were analyzed using SPSS. RESULTS: There were no differences in expert-based assessments between groups at the pretest. All three groups showed significant improvements in expert-based scores between the pretests and post-tests as well as between pretests and retention tests (P < 0.0001). Instructor-led teaching and IVBI were equally effective initially for teaching this skill to naive medical students and showed better performance than NIVBI (P < 0.0001 each). At retention, IVBI displayed superior performance compared to NIVBI and the instructor-led group (P < 0.0001 each). CONCLUSIONS: Our result showed that video-based instruction could be as effective as instructor-led teaching in acquiring basic surgical skills. These findings support the idea that with thoughtful incorporation into technical skill curricula, video-based instruction may efficiently use faculty time and serve as a helpful adjunct for basic surgical skills training.
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Estudiantes de Medicina , Humanos , Estudios Prospectivos , Método Simple Ciego , Competencia Clínica , Curriculum , EnseñanzaRESUMEN
Significant work has been done in recent years on treatment strategies for distal femur fractures. Inclusive reviews on periprosthetic fractures of distal femur have been carried out recently, but there is a lack of such reviews on the subject of native distal femur fractures in the recent literature. In this narrative review, we are set out to address the latest updates on geriatric non-periprosthetic distal femur fractures, and perform a rapid review over different treatment options, arriving at a summarized proposed treatment algorithm.
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Fracturas del Fémur , Fracturas Periprotésicas , Anciano , Placas Óseas , Fracturas del Fémur/cirugía , Fémur , Fijación Interna de Fracturas , Humanos , Fracturas Periprotésicas/cirugíaRESUMEN
OBJECTIVES: To investigate the therapeutic effects of sumatriptan in a rat model of spinal cord injury (SCI) and possible anti-inflammatory and analgesic mechanisms underlying this effect. METHODS: Using an aneurysm mini-clip model of contusive SCI, T9-10 laminectomies were performed for 60 male rats. Animals were divided into six experimental groups (n = 10 per group) as follows: a minocycline administered positive control group, a saline-vehicle negative control group, a sham-operated group, and three experimental groups which received separate doses of sumatriptan (0.1, 0.3 and 1 mg/kg). Behavioural assessments were used to evaluate locomotor activity and neuropathic pain for 28 days. At the end of the study, spinal cord tissues were collected from sacrificed animals for histopathological analysis. Levels of calcitonin gene-related peptide (CGRP) and two pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1ß) were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: Sumatriptan significantly (P < 0.001) improved the locomotor activity in SCI group. Sumatriptan was also more effective than the positive control, i.e. minocycline (0.3 mg/kg). Additionally, sumatriptan and minocycline similarly attenuated the mechanical and thermal allodynia in SCI (P < 0.001). TNF-α, IL-1ß and CGRP levels in sumatriptan- and minocycline-treated groups significantly (P < 0.001) decreased compared to controls. Histopathological analysis also revealed a markedly improvement in hemorrhage followed by inflammatory cell invasion, neuronal vacuolation, and cyst formation in both sumatriptan- and minocycline-treated groups compared to control animals. CONCLUSIONS: Sumatriptan improves functional recovery from SCI through its anti-inflammatory effects and reducing pro-inflammatory and pain mediators.
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Antiinflamatorios/farmacología , Locomoción/efectos de los fármacos , Neuralgia , Traumatismos de la Médula Espinal , Sumatriptán/farmacología , Analgésicos/farmacología , Animales , Modelos Animales de Enfermedad , Inflamación/etiología , Masculino , Neuralgia/etiología , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/patologíaRESUMEN
BACKGROUND: Assessment of the association of various lifestyle factors and wellness and health status in patients with Behcet's disease was the main goal of this study. METHODS: Demographic information, body mass index, smoking habit, mood status, sleep quality, physical activity levels, nutritional data, symptoms, signs, laboratory findings and patient reported outcome (self-rated wellness and health) in 52 patients with Behcet's disease were collected in this cross-sectional study. A multivariable linear regression model was used to assess the association of self-rated wellness and health status and lifestyle factors, adjusted for age, sex, BMI, major symptoms and signs, as well as laboratory findings. RESULTS: Female to male ratio was 21/31, and the mean age of participants was 44 years. Mean self-rated wellness and health score was 14.6 out of 20. Oral and genital aphthous, ocular involvement, pathergy, and skin involvement were observed in 100, 52, 92, 36.5, and 9.5% of patients, respectively. The mean values of sleep, mood and nutrition quality scores were 17.7 (out of 70), 13.8 (out of 35), and 9 (out of 21), respectively. Univariable regression analysis showed a significant association between sleep quality, mood status, and disease duration, with patients' status in terms of self-rated wellness and health. In multivariable linear regression, sleep quality was the only significant predictive variable associated with self-rated wellness and health. CONCLUSION: Sleep quality was the most important factor associated with low self-rated wellness and health status in patients with Behcet's disease.
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INTRODUCTION: Carbon dioxide (CO2) laser surgery as a conservative tool plays a peculiar role in the management of head and neck cancer. Numerous patients who were candidates for transoral laryngeal microsurgery have forced us to eliminate frozen-section evaluation of surgical margins and use a magnified view of the larynx. The present study evaluated surgeon-judged negative margins with permanent microscopic pathologic evaluation. MATERIALS AND METHODS: In this cross-sectional study, we evaluated the permanent pathologic margins of the resected laryngeal specimen which were considered negative by judgment of surgeons. Patients consisted of 61 pathologic proven T1-T2 laryngeal squamous cell carcinoma (SCC) cases. In all patients, tumor resection was performed via a transoral route with CO2 laser, and no residual laryngeal tumor was observed according to judgment of the surgeon. The patients with positive margin (s) underwent another resection. Patients were followed up for 18 months for tumor recurrence. RESULTS: The obtained results demonstrated that pathologic margins were reported in 6 patients, with the deep margin being the most common positive margin. During the 18-month follow-up, 8 cases of recurrence were detected. CONCLUSION: Judgment of the surgeon was in agreement with permanent pathologic evaluation in transoral laryngeal laser resection at the early stages of laryngeal SCC in most cases. Nevertheless, it is suggested that further direct studies be conducted to evaluate the frozen section on oncologic outcomes in transoral laser surgery for laryngeal cancer.
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Melatonin is a neurohormone secreted principally by the pineal gland. This molecule has various pharmacological properties including improving immune system, prevent cancer, anti-aging, and anti-oxidant effects. The anticonvulsant effects of melatonin have been proved by previous studies. Adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels are considered as an important target in the seizure modulation. The aim of the present study was to investigate the anticonvulsant effect of melatonin in pentylenetetrazole (PTZ)-induced seizures in mice, focusing on its ability to regulate KATP channels. Acute intraperitoneal administration of melatonin (40 and 80 mg/kg) increased clonic seizure threshold induced by intravenous administration of PTZ. Melatonin (40 and 80 mg/kg) increased the latency of clonic seizure and reduced its frequency in mice receiving an intraperitoneal injection of PTZ. Administration of glibenclamide, a KATP channels blocker, before intravenous injection of PTZ reduced melatonin anticonvulsant effect. Diazoxide and cromakalim, as KATP channels openers, increased antiseizure effect of melatonin in PTZ model of seizures. These findings suggest that the antiseizure effect of melatonin probably is gained through increasing the opening of KATP channels.
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Anticonvulsivantes/farmacología , Canales KATP/efectos de los fármacos , Melatonina/farmacología , Convulsiones/tratamiento farmacológico , Animales , Anticonvulsivantes/administración & dosificación , Cromakalim/farmacología , Diazóxido/farmacología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Gliburida/farmacología , Inyecciones Intraperitoneales , Canales KATP/metabolismo , Masculino , Melatonina/administración & dosificación , Ratones , Pentilenotetrazol , Convulsiones/fisiopatologíaRESUMEN
BACKGROUND: Metformin ameliorates non-histamine-mediated itch. We have recently reported that the nitric oxide (NO) pathway is involved in chloroquine (CQ)-induced scratching behavior. Here we investigated the involvement of the NO pathway in the antipruritic effect of metformin on CQ-induced itch. METHODS: Metformin (5-200 mg/kg, given intraperitoneally [i.p.]) was injected 4 h before CQ (400 µg/site, given intradermally [i.d.]) or compound 48/80 (100 µg/site, i.d.). A nonspecific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 and 10 mg/kg, i.p.), or an NO precursor, L-arginine (10 and 100 mg/kg, i.p.) was administered 30 min before injection of CQ. A neural NOS (nNOS) inhibitor, 7-nitroindazole (7-NI; 1 and 10 nmol/site, i.d.) was concurrently administered with CQ. The scratching behavior was recorded for 30 min following the injection of CQ. We studied the changes in skin and spinal nitrite levels after treatments. RESULTS: Our results showed that metformin (100 and 200 mg/kg) significantly reduced the CQ-induced scratching behavior but not the compound 48/80-induced scratching behavior. L-Arginine inhibited the antipruritic effect of metformin, while L-NAME and 7-NI significantly potentiated the inhibitory effects of a subeffective dose of metformin on the CQ-induced scratching behavior. The skin but not the spinal nitrite level was significantly increased after CQ administration. The elevated cutaneous nitrite level was reversed by effective doses of either metformin or 7-NI, but not by the subeffective doses of metformin + 7-NI. CONCLUSION: Acute injection of metformin significantly inhibits CQ-induced scratching behavior. This effect is mediated through inhibition of the NO pathway, especially by inhibiting the dermal nNOS enzyme.
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Antipruriginosos/uso terapéutico , Cloroquina/efectos adversos , Metformina/uso terapéutico , Óxido Nítrico/biosíntesis , Prurito/tratamiento farmacológico , Piel/efectos de los fármacos , Animales , Antipruriginosos/metabolismo , Antipruriginosos/farmacología , Cloroquina/farmacología , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/farmacología , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Inyecciones , Metformina/metabolismo , Metformina/farmacología , Ratones , Prurito/inducido químicamente , Prurito/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/inervación , Piel/metabolismoRESUMEN
Lipopolysaccharide (LPS) increases inflammatory cytokines of the brain and deregulates the mitochondrial function, thus could increase the seizure susceptibility. Studies have shown that minocycline has neuroprotective and antioxidant properties. In this study, we aimed to evaluate the anticonvulsant properties of minocycline in LPS-treated animals and the possible involvement of nitric oxide and mitochondrial pathways. In a PTZ model of seizure in mice, minocycline was administrated to LPS-treated mice. Then followed by co-injection of its sub-effective dose and NOS inhibitors including 7-Nitroindazole (7-NI), aminoguanidine (AG) and L-NG-Nitroarginine methyl ester (L-NAME) to evaluate the changes in seizure threshold and the possible involvement of nitrergic system. Molecular assessments were used to evaluate the effects of each treatment on inflammation and mitochondrial function in the brain. LPS-treated animals had lower seizure threshold compared to intact animals; injection of minocycline (80â¯mg/kg) to LPS-treated mice reversed this effect. Co-injection of sub-effective doses of minocycline (40â¯mg/kg) and L-NAME to LPS-treated animals significantly increased seizure threshold. We observed that co-treatment of minocycline and AG dissimilar to 7-NI could increase the seizure threshold of LPS-treated animals. L-arginine reversed the anticonvulsant effect of minocycline. Also, molecular evaluations showed that LPS could increase the ATP levels, GSH levels, and reactive oxygen species formation. However, minocycline at both doses significantly reversed the effect of LPS. Minocycline counteracts the proconvulsant effects of LPS through regulating of mitochondrial function and decreasing of neuro-inflammation. Also, co-administration of minocycline and i-NOS inhibitors could intensify anticonvulsant effects of minocycline.
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Lipopolisacáridos/farmacología , Minociclina/farmacología , Mitocondrias/efectos de los fármacos , Óxido Nítrico/metabolismo , Convulsiones/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Minociclina/uso terapéutico , Mitocondrias/metabolismo , Mitocondrias/patología , NG-Nitroarginina Metil Éster/farmacología , Convulsiones/metabolismo , Convulsiones/patologíaRESUMEN
Acute doses of topiramate (TPM) have been shown to reduce immobility time in the mice forced swimming test (FST) through inhibition of the nitric oxide (NO) pathway. Adenosine triphosphate-sensitive potassium (KATP) channels are known to have an active role in depression. This study investigates the potential participation of KATP channels in the antidepressant-like effect of TPM through the stimulatory effects of NO. FST and tail suspension tests (TST) were applied to adult male mice for assessment of the antidepressant-like activity of TPM. Different doses of glibenclamide and cromakalim were also applied in order to investigate the involvement of KATP channels. Fluoxetine was used as a positive control for evaluation of antidepressant-like effects. In addition, each animal's locomotor activity was evaluated by the open-field test (OFT). TPM (30 mg/kg intraperitoneal (i.p.)) had a significant reductive effect on the immobility behavior similar to fluoxetine (20 mg/kg). Co-administration of sub-effective doses of glibenclamide (1 mg/kg i.p.) and TPM (10 mg/kg i.p.) led to significant synergistic effects in FST and TST. Additionally, the results showed that administration of the sub-effective dose of cromakalim (0.1 and 0.3 mg/kg i.p.) blocked the antidepressant-like effects of TPM (30 mg/kg i.p.) in both tests. These interventions had no impact on the locomotor movement of mice in OFT. This study shows that the antidepressant-like activity of TPM may potentially be mediated by the blocking of the KATP channels.
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Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Canales KATP/metabolismo , Locomoción/efectos de los fármacos , Topiramato/farmacología , Animales , Cromakalim/farmacología , Relación Dosis-Respuesta a Droga , Gliburida/farmacología , Suspensión Trasera , Masculino , Ratones , NataciónRESUMEN
Non-traumatic subluxation of atlanto-axial joint known as Grisel's syndrome is a rare condition. The pathogenesis of Grisel syndrome in not clear but it seems laxity of cervical ligaments in children and an inflammatory process in neck might cause the syndrome. Here we present a case of Grisel's syndrome, a 9 -year- old boy presented with torticollis and discuss about clinical radiological and treatment aspects of the syndrome.
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BACKGROUND: Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action. METHODS: After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4min was evaluated. All drugs were given intraperitoneally (ip). RESULTS: Selegiline (10mg/kg) decreased the immobility time in the FST similar to fluoxetine (20mg/kg). Pretreatment with l-arginine (NO precursor, 750mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents. CONCLUSIONS: It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of l-arginine-NO-cyclic guanosine monophosphate pathway.
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Antidepresivos/farmacología , GMP Cíclico/metabolismo , Pérdida de Tono Postural/efectos de los fármacos , Óxido Nítrico/metabolismo , Selegilina/farmacología , Natación , Animales , Arginina/farmacología , Sinergismo Farmacológico , Fluoxetina/farmacología , Guanidinas/farmacología , Hipocampo/metabolismo , Indazoles/farmacología , Masculino , Azul de Metileno/farmacología , Ratones , Actividad Motora/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Nitritos/metabolismo , Corteza Prefrontal/metabolismo , Selegilina/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Citrato de Sildenafil/farmacologíaRESUMEN
Clinical use of vincristine (VCR), an effective chemotherapeutic agent, has been limited due to its peripheral neuropathy toxicity. Sumatriptan, which is an anti-migraine agent is a specific agonist for 5-hydroxytryptamine 1B, 1D (5HT1B, 1D) receptors. Several studies have shown that sumatriptan exerts anti-inflammatory and immunomodulatory properties. This study aimed to investigate the effects of sumatriptan on VCR-induced peripheral neuropathy in a rat model. Male Wistar rats were intraperitoneally injected with VCR and normal saline four times per week for 2 weeks. In the treatment group, sumatriptan (1â¯mg/kg) was administered intraperitoneally 30â¯min prior to VCR injection every day. Mortality rate, weight variations and histopathological changes were monitored. Hot plate, tail flick and motor nerve conduction velocity (MNCV) tests were used to evaluate sensory and motor neuropathy. Levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and caspase-3 in the dorsal ganglion root were assessed by quantitative reverse transcription-PCR (qRT-PCR). Moreover, the protein levels of p65 nuclear factor kappa B (NF-
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Modelos Animales de Enfermedad , Fármacos Neuroprotectores/uso terapéutico , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/prevención & control , Sumatriptán/uso terapéutico , Vincristina/toxicidad , Animales , Antineoplásicos Fitogénicos/toxicidad , Masculino , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Enfermedades del Sistema Nervioso Periférico/patología , Ratas , Ratas Wistar , Agonistas del Receptor de Serotonina 5-HT1/uso terapéuticoRESUMEN
Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and impaired serotonin signaling has been linked to a variety of itch conditions. Intradermal injection of 5-HT induces scratching behavior in mice through stimulation of 5-HT receptors. Previous studies have demonstrated that selective 5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission. We have also reported that sumatriptan suppresses chloroquine-induced itch. Therefore, we investigated if sumatriptan has inhibitory effects on serotonin-induced itch in mice. Here, we show that intradermal and intraperitoneal administration of sumatriptan significantly reduce 5-HT-induced scratching behavior in mice. While intradermal injection of GR-127935, a selective 5-HT1B/1D receptors antagonist, reverses the anti-pruritic effects of sumatriptan. In addition, we show that intradermal and intraperitoneal naltrexone (NTX), a non-specific opioid receptor antagonist, and methylnaltrexone (MNTX), a peripherally acting opioid receptor antagonist, significantly decrease the 5-HT-induced scratching behavior. Additionally, combined treatment with sub-effective doses of sumatriptan and an opioid receptor antagonist, naltrexone, decreases 5-HT-evoked scratching responses. We conclude that sumatriptan inhibits 5-HT-induced itch by activating the peripheral 5-HT1B/1D receptors. Moreover, peripheral opioid receptors have a role in serotonin-induced itch, and anti-pruritic effects of sumatriptan seem to involve the opioid system. These data suggest that 5-HT1B/1D receptors agonists maybe useful to treat a variety of pathologic itch conditions with impaired serotonergic system.
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Péptidos Opioides/metabolismo , Prurito/tratamiento farmacológico , Receptores de Serotonina 5-HT1/metabolismo , Agonistas del Receptor de Serotonina 5-HT1/uso terapéutico , Sumatriptán/uso terapéutico , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada/métodos , Humanos , Inyecciones Intradérmicas , Masculino , Ratones , Naltrexona/análogos & derivados , Naltrexona/farmacología , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/uso terapéutico , Oxadiazoles/farmacología , Piperazinas/farmacología , Prurito/inducido químicamente , Prurito/patología , Compuestos de Amonio Cuaternario/farmacología , Compuestos de Amonio Cuaternario/uso terapéutico , Serotonina/administración & dosificación , Serotonina/metabolismo , Antagonistas de la Serotonina/farmacologíaRESUMEN
Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/cyclic guanosine monophosphate pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity. Thus, we aimed to investigate the effect of sumatriptan on CQ-induced scratching. We used the rostral back model of itch. Chloroquine was injected intradermally into the rostral back of NMRI mice, and the scratching behavior was evaluated by measuring the number of bouts over 30 min. We evaluated the effect of sumatriptan and combination of sumatriptan and a non-selective NO synthase inhibitor, L-N-nitro arginine methyl ester (L-NAME), on the scratching behavior. Additionally, the changes of skin, hippocampus, and cortical nitrite level after different treatments were studied. Intraperitoneal and intradermal sumatriptan attenuates CQ-induced itch which reversed by GR-127935, the selective 5-HTR1b and 5-HTR1d antagonist. Co-administration of subeffective doses of sumatriptan and L-NAME significantly decreases the scratching behavior. Intradermal injection of CQ significantly increases the intradermal nitrite levels while it does not have any significant effects on hippocampal or cortical nitrite concentrations. Likewise, the effective doses of intraperitoneal and intradermal sumatriptan significantly reduce intradermal nitrite levels. We concluded that sumatriptan suppresses CQ-induced itch most likely by activating 5-HT1b/1d receptors. This effect probably mediates through NO pathway.