PMID- 27596139 OWN - NLM STAT- MEDLINE DCOM- 20171002 LR - 20220317 IS - 1471-2253 (Electronic) IS - 1471-2253 (Linking) VI - 16 IP - 1 DP - 2016 Sep 5 TI - Anti-nerve growth factor antibody attenuates chronic morphine treatment-induced tolerance in the rat. PG - 73 LID - 10.1186/s12871-016-0242-x [doi] LID - 73 AB - 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 naive 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 mug of anti-NGF and the other with 10 mg/kg of morphine + 10 mug 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. FAU - Cheppudira, Bopaiah P AU - Cheppudira BP AD - Burn Injuries Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, 78234, USA. bopaiah.p.cheppudira.vol@mail.mil. FAU - Trevino, Alex V AU - Trevino AV AD - Burn Injuries Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, 78234, USA. FAU - Petz, Lawrence N AU - Petz LN AD - Department of Clinical Investigation, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, 78234, USA. FAU - Christy, Robert J AU - Christy RJ AD - Burn Injuries Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, 78234, USA. FAU - Clifford, John L AU - Clifford JL AD - Burn Injuries Task Area, United States Army Institute of Surgical Research, 3698 Chambers Pass, San Antonio Military Medical Center, Fort Sam Houston, San Antonio, Texas, 78234, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20160905 PL - England TA - BMC Anesthesiol JT - BMC anesthesiology JID - 100968535 RN - 0 (Antibodies, Neutralizing) RN - 76I7G6D29C (Morphine) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Administration, Cutaneous MH - Animals MH - Antibodies, Neutralizing/administration & dosage/*pharmacology MH - Drug Tolerance/*immunology MH - Injections, Intraperitoneal MH - Male MH - Morphine/administration & dosage/*immunology/pharmacology MH - Nerve Growth Factor/*immunology/metabolism MH - Pain Measurement/drug effects MH - Rats MH - Spinal Cord/metabolism PMC - PMC5011970 OTO - NOTNLM OT - Anti-NGF OT - Hargreaves' test OT - Morphine OT - Nerve growth factor OT - Tolerance EDAT- 2016/09/07 06:00 MHDA- 2017/10/03 06:00 PMCR- 2016/09/05 CRDT- 2016/09/07 06:00 PHST- 2016/03/04 00:00 [received] PHST- 2016/08/25 00:00 [accepted] PHST- 2016/09/07 06:00 [entrez] PHST- 2016/09/07 06:00 [pubmed] PHST- 2017/10/03 06:00 [medline] PHST- 2016/09/05 00:00 [pmc-release] AID - 10.1186/s12871-016-0242-x [pii] AID - 242 [pii] AID - 10.1186/s12871-016-0242-x [doi] PST - epublish SO - BMC Anesthesiol. 2016 Sep 5;16(1):73. doi: 10.1186/s12871-016-0242-x.