Perioperative use of physostigmine to reduce opioid consumption and peri-incisional hyperalgesia: a randomised controlled trial

Klivinyi, Christoph; Rumpold-Seitlinger, Gudrun; Dorn, Christian; Sampl, Larissa; Sivro, Nikki; Lang-Illievich, Kordula; Fleck, Sabine; Farzi, Sylvia; Bornemann‐Cimenti, Helmar

doi:10.1016/j.bja.2020.10.039

Cited by 9 publications

(10 citation statements)

References 29 publications

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Section: Discussionmentioning

confidence: 99%

“…Systemic and spinal administration of acetylcholinesterase inhibitors and muscarinic receptor agonists can produce an analgesic effect [ 9 , 12 , 15 ]. Intrathecal injection of neostigmine and physostigmine produces dose-dependent antinociception effects and relieves allodynia in a dose-related manner [ 9 , 12 , 15 ]. The analgesic effect caused by neostigmine is mainly related to the release of acetylcholine and the activation of the muscarinic-acetylcholine receptor, as atropine blocks the muscarinic-acetylcholine receptor and antagonizes the analgesic effect [ 9 , 12 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Intrathecal injection of neostigmine and physostigmine produces dose-dependent antinociception effects and relieves allodynia in a dose-related manner [ 9 , 12 , 15 ]. The analgesic effect caused by neostigmine is mainly related to the release of acetylcholine and the activation of the muscarinic-acetylcholine receptor, as atropine blocks the muscarinic-acetylcholine receptor and antagonizes the analgesic effect [ 9 , 12 , 15 ]. However, when neostigmine is used as a nondepolarizing muscle relaxant antagonist, it is always used in combination with atropine as it antagonizes the muscarinic-acetylcholine receptor activity [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of muscarinic receptor agonists and acetylcholinesterase inhibitors in the spinal cord can also result in antinociception [ 31 ]. The perioperative administration of physostigmine can reduce opioid consumption and peri-incisional mechanical allodynia [ 12 ]. Intrathecal neostigmine alone, or combined with clonidine, or opioids, has been successfully used for postoperative analgesic effects and pain relief [ 32 ], as it produces a longer effect with greater cardiovascular system reliability and fewer side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Ach is released in response to pain stimuli at the spinal cord and brain stem level [ 11 ]. Cholinesterase inhibitor physostigmine has been shown to relieve clinical postoperative pain [ 12 ]. And neostigmine, a clinical cholinesterase inhibitor, is widely used as an anesthetic to reverse nondepolarizing neuromuscular blockers.…”

Section: Introductionmentioning

confidence: 99%

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Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats

Huang

Xiu-juan

Zhang

et al. 2022

Pain Research and Management

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Background. 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–Dawley 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 μg), neostigmine (0.3, 1, 3, and 10 μg) 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 minutes 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 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. Results. Intrathecally administered pentazocine (3, 10, 30, and 100 μg) and neostigmine (0.3, 1, 3, and 10 μg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 μg) and neostigmine (0.3, 1, 3, and 10 μg) 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.

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