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Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. Objectives. To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. Methods. Sprague\u2013Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100\u2009\u03bcg), neostigmine (0.3, 1, 3, and 10\u2009\u03bcg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30\u2009minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30\u2009minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. Results. Intrathecally administered pentazocine (3, 10, 30, and 100\u2009\u03bcg) and neostigmine (0.3, 1, 3, and 10\u2009\u03bcg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100\u2009\u03bcg) and neostigmine (0.3, 1, 3, and 10\u2009\u03bcg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. Conclusions. All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord.<\/jats:p>","DOI":"10.1155\/2022\/4819910","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T22:35:39Z","timestamp":1652913339000},"page":"1-12","source":"Crossref","is-referenced-by-count":4,"title":["Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats"],"prefix":"10.1155","volume":"2022","author":[{"given":"Huiying","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion, Guangzhou First People\u2019s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-8246","authenticated-orcid":true,"given":"Xiaohui","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China"},{"name":"Department of Anesthesiology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation. 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