Anti-nerve growth factor antibody attenuates chronic morphine treatment-induced tolerance in the rat.
BMC Anesthesiol
; 16(1): 73, 2016 09 05.
Article
en En
| MEDLINE
| ID: mdl-27596139
BACKGROUND: Nerve growth factor (NGF) is known to induce inflammation and pain; however its role in opioid-induced tolerance has not been studied. This study investigated the effects of an anti-NGF neutralizing antibody on the development of tolerance following chronic morphine treatment in naïve rats. METHODS: Four groups of rats were used in this study; one treated with saline alone, one with 10 mg/kg of morphine, one with 10 µg of anti-NGF and the other with 10 mg/kg of morphine + 10 µg of anti-NGF, twice per day for 5 days. The route of treatment was subcutaneous (S.C.) for morphine and saline, and intraperitoneal (i.p.) for anti-NGF. Response to a noxious thermal stimulus during the course of drug treatment was assessed (Hargreaves' test). Further, the change in the NGF levels in the lumbar spinal cord was measured by ELISA. RESULTS: Our results showed that repeated administration of morphine produced an apparent tolerance which was significantly attenuated by co-administration of anti-NGF (P < 0.001). Additionally, the area under the curve (AUC) of the analgesic effect produced by the combination of morphine and anti-NGF was significantly (P < 0.001) greater than for saline controls and chronic morphine treated rats. Moreover, the level of NGF in the spinal cord of chronic morphine treated rats was significantly higher (P < 0.05) than in both the saline control group and the group receiving simultaneous administration of anti-NGF with morphine. These results indicate that anti-NGF has the potential to attenuate morphine-induced tolerance behavior by attenuating the effects of NGF at the spinal level. CONCLUSION: Taken together, our study strongly suggests that the NGF signaling system is a potential novel target for treating opioid-induced tolerance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Nervioso
/
Tolerancia a Medicamentos
/
Anticuerpos Neutralizantes
/
Morfina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
BMC Anesthesiol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido