Celecoxib reduces hyperalgesia and tactile allodynia in diabetic rats.
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.
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico. Electronic address: iselajua22@yahoo.com.mx.
Isela E
IE
Juárez-Rojop
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico.
Paulina E
PE
Morales-Hernández
División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Mexico.
Carlos A
CA
Tovilla-Zárate
División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma de Tabasco, Comalcalco, Mexico.
Deysi Y
DY
Bermúdez-Ocaña
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico.
Jorge E
JE
Torres-Lopez
División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Mexico.
Jorge L
JL
Ble-Castillo
Facultad de Medicina, Universidad Nacional Autónoma de México, Universidad 3000, Ciudad Universitaria, Coyoacán, México, D.F., Mexico.
Juan C
JC
Díaz-Zagoya
Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, México, D.F., Mexico.
Vinicio
V
Granados-Soto
D000818:Animals; D000068579:Celecoxib / Q000627:therapeutic use*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
D052246:Cyclooxygenase 2 Inhibitors; D000068579:Celecoxib
Celecoxib; Hypersensitivity; Neuropathic pain; Opioid receptors; Tactile allodynia