Anti-nerve growth factor antibody attenuates chronic morphine treatment-induced tolerance in the rat

BMC Anesthesiology

Research Article

Bopaiah P. Cheppudira¹  Alex V. Trevino¹  Robert J. Christy¹  John L. Clifford¹  Lawrence N. Petz² 

[1] Burn Injuries Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, 78234, San Antonio, Texas, USA;Department of Clinical Investigation, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, 78234, San Antonio, Texas, USA;

关键词: Nerve growth factor;    Anti-NGF;    Morphine;    Tolerance;    Hargreaves’ test;   

DOI  :  10.1186/s12871-016-0242-x

 received in 2016-03-04, accepted in 2016-08-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNerve 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.MethodsFour 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.ResultsOur 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.ConclusionTaken together, our study strongly suggests that the NGF signaling system is a potential novel target for treating opioid-induced tolerance.

【 授权许可】

CC BY   
© The Author(s). 2016