Endocannabinoid System Attenuates Oxaliplatin-Induced Peripheral Sensory Neuropathy Through the Activation of CB1 Receptors
| العنوان: | Endocannabinoid System Attenuates Oxaliplatin-Induced Peripheral Sensory Neuropathy Through the Activation of CB1 Receptors |
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| المؤلفون: | Bruno Wesley de Freitas Alves, Jaime Eduardo Cecílio Hallak, Mariana Lima Vale, Jonas Costa de França, Mario Roberto Pontes Lisboa, José Alexandre de Souza Crippa, Antonio Waldo Zuardi, Cristiane Maria Pereira da Silva, Roberto C. P. Lima-Júnior, Francisco Rafael Alves Santana Cesário, Diego Bernarde Souza Dias, Anamaria Falcão Pereira, Nylane M.N. Alencar, Amanda Rocha de Oliveira, Karoline Luanne Santos de Menezes |
| المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | AM251, Cannabinoid receptor, business.industry, General Neuroscience, medicine.medical_treatment, Spinal trigeminal nucleus, CANABINOIDES, Pharmacology, Toxicology, Endocannabinoid system, Nociception, medicine.anatomical_structure, Allodynia, nervous system, medicine, lipids (amino acids, peptides, and proteins), Cannabinoid, medicine.symptom, business, Cannabidiol, psychological phenomena and processes, medicine.drug |
| الوصف: | Oxaliplatin-induced neurotoxicity is expressed as a dose-limiting peripheral sensory neuropathy (PSN). Cannabinoid substances have been investigated for the analgesic effect. This study aimed to investigate the role of cannabinoid receptors in oxaliplatin-associated PSN. Swiss male mice received nine oxaliplatin injections (2 mg/kg, i.v.). Mechanical and thermal nociceptive tests were performed for 56 days. CB1, CB2, and c-Fos expression were assessed in dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), spinal trigeminal nucleus caudalis (Sp5C), and periaqueductal gray (PAG). Iba-1 expression was assessed in DRG and ATF3 in TG. Cannabidiol (10 mg/kg, p.o.) or a CB1/CB2 non-selective agonist (WIN 55,212–2; 0.5 mg/kg, s.c.) or AM251 (CB1 antagonist) or AM630 (CB2 antagonist) (3 mg/kg, i.p.) were injected before oxaliplatin. Oxaliplatin increased CB1 in DRG, SC, TG, Sp5C, and ventrolateral PAG, with no interference in CB2 expression. Cannabidiol increased CB1 in DRG, reduced mechanical hyperalgesia and c-Fos expression in DRG and SC. Additionally, WIN 55,212–2 increased CB1 in DRG, reduced mechanical hyperalgesia, cold allodynia and c-Fos expression in DRG and SC. CB1 blockage hastened the cold allodynia response, but the CB2 antagonist failed to modulate the oxaliplatin-induced nociceptive behavior. Oxaliplatin also increased Iba-1 in DRG, suggesting immune response modulation which was reduced by cannabidiol and enhanced by AM630. The modulation of the endocannabinoid system, through the CB1 receptor, attenuates the oxaliplatin-associated PNS. The activation of the endocannabinoid system could be considered as a therapeutic target for controlling oxaliplatin-associated neuropathy. |
| تدمد: | 1476-3524 1029-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84d3b929c8d62756704c6a7a8f08ba8fTest https://doi.org/10.1007/s12640-021-00442-xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....84d3b929c8d62756704c6a7a8f08ba8f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14763524 10298428 |
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