Isela E Juárez-Rojop1, Paulina E Morales-Hernández2, Carlos A Tovilla-Zárate3, Deysi Y Bermúdez-Ocaña3, Jorge E Torres-Lopez2, Jorge L Ble-Castillo2, Juan C Díaz-Zagoya4, Vinicio Granados-Soto5. 1. División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico. Electronic address: iselajua22@yahoo.com.mx. 2. División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico. 3. División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Mexico. 4. Facultad de Medicina, Universidad Nacional Autónoma de México, Universidad 3000, Ciudad Universitaria, Coyoacán, México, D.F., Mexico. 5. Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, México, D.F., Mexico.
Abstract
BACKGROUND: In the present study we determined the antihyperalgesic and antiallodynic effect of celecoxib in diabetic rats as well as the possible participation of opioid receptors in the mechanism of action of celecoxib in these rats. METHODS: Experimental diabetes was induced by streptozotocin. Formalin (0.5%) was used to produce hyperalgesia in non-diabetic and diabetic rats. von Frey filaments were used to determine the 50% withdrawal threshold in diabetic rats. RESULTS: Oral administration of celecoxib (0.3-30 mg/kg) reduced formalin-induced nociceptive behavior during phase 2. Systemic pre-treatment (-10 min) with naltrexone (3mg/kg) prevented celecoxib-induced antihyperalgesia in formalin-treated diabetic rats. Furthermore, naltrexone as well as the δ and κ opioid receptor antagonists naltrindole (3mg/kg) and 5'-guanidino naltrindole (1mg/kg), respectively, fully prevented celecoxib-induced antihyperalgesia (10mg/kg) in formalin-treated non-diabetic and diabetic rats. Furthermore, celecoxib (0.3-30 mg/kg) produced an antiallodynic effect in diabetic rats. Pre-treatment with naltrexone (3mg/kg) fully prevented the antiallodynic effect of celecoxib at 0.3, 3 and 10mg/kg. In contrast, this dose of naltrexone only partially prevented the antiallodynic effect of celecoxib 30 mg/kg. Naltrexone and naltrindole (3mg/kg), but not 5'-guanidino naltrindole (1mg/kg), fully prevented the antiallodynic effect of celecoxib in diabetic rats. CONCLUSIONS: Data suggest that celecoxib produces an antihyperalgesic and antiallodynic effect in diabetic rats. These effects seem to result from activation of μ, δ and κ opioid receptors for antinociception and μ and δ for antiallodynia. Celecoxib could be useful to treat neuropathic pain in diabetic patients.
BACKGROUND: In the present study we determined the antihyperalgesic and antiallodynic effect of celecoxib in diabeticrats as well as the possible participation of opioid receptors in the mechanism of action of celecoxib in these rats. METHODS: Experimental diabetes was induced by streptozotocin. Formalin (0.5%) was used to produce hyperalgesia in non-diabetic and diabeticrats. von Frey filaments were used to determine the 50% withdrawal threshold in diabeticrats. RESULTS: Oral administration of celecoxib (0.3-30 mg/kg) reduced formalin-induced nociceptive behavior during phase 2. Systemic pre-treatment (-10 min) with naltrexone (3mg/kg) prevented celecoxib-induced antihyperalgesia in formalin-treated diabeticrats. Furthermore, naltrexone as well as the δ and κ opioid receptor antagonists naltrindole (3mg/kg) and 5'-guanidino naltrindole (1mg/kg), respectively, fully prevented celecoxib-induced antihyperalgesia (10mg/kg) in formalin-treated non-diabetic and diabeticrats. Furthermore, celecoxib (0.3-30 mg/kg) produced an antiallodynic effect in diabeticrats. Pre-treatment with naltrexone (3mg/kg) fully prevented the antiallodynic effect of celecoxib at 0.3, 3 and 10mg/kg. In contrast, this dose of naltrexone only partially prevented the antiallodynic effect of celecoxib 30 mg/kg. Naltrexone and naltrindole (3mg/kg), but not 5'-guanidino naltrindole (1mg/kg), fully prevented the antiallodynic effect of celecoxib in diabeticrats. CONCLUSIONS: Data suggest that celecoxib produces an antihyperalgesic and antiallodynic effect in diabeticrats. These effects seem to result from activation of μ, δ and κ opioid receptors for antinociception and μ and δ for antiallodynia. Celecoxib could be useful to treat neuropathic pain in diabeticpatients.
Authors: Christoforos Tsantoulas; Sergio Laínez; Sara Wong; Ishita Mehta; Bruno Vilar; Peter A McNaughton Journal: Sci Transl Med Date: 2017-09-27 Impact factor: 17.956