Enhanced analgesic cholinergic tone in the spinal cord in a mouse model of neuropathic pain

Dhanasobhon, Dhanasak; Medrano, Maria‐Carmen; Becker, Léa J.; Moreno-López, Yunuen; Kavraal, S.; Bichara, Charlotte; Schlichter, Rémy; Inquimbert, Perrine; Yalçın, İpek; Cordero-Erausquin, Matilde

doi:10.1016/j.nbd.2021.105363

Cited by 10 publications

(6 citation statements)

References 63 publications

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…A recent preclinical study in mice demonstrated that following nerve injury, cholinergic tone might increase, and that downstream cholinergic signaling is altered under neuropathic conditions ( Dhanasobhon et al, 2021 ). In addition, the cholinesterase inhibitor, donepezil, induces analgesia in human patients ( Basnet et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

The efficacy of duloxetine depends on spinal cholinergic plasticity in neuropathic pain model rats

Kato

Suto

Obata

et al. 2022

IBRO Neuroscience Reports

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“…All these compounds have been tested in the three animal models of PNP. Most of the compounds induced antinociceptive effects, both on mechanical and thermal hypersensitivity [20,[31][32][33][34][35][36][37]. A low dose of neostigmine (intrathecal injection, 0.3 ng) did not produce significant antinociceptive effects [38].…”

Section: Pharmacological Compounds Increasing the Acetylcholine Neuro...mentioning

confidence: 98%

Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies

Montigné,

Balayssac

2023

Pharmaceuticals

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Neuropathic pain affects about 7–8% of the population, and its management still poses challenges with unmet needs. Over the past decades, researchers have explored the cholinergic system (muscarinic and nicotinic acetylcholine receptors: mAChR and nAChR) and compounds targeting these receptors as potential analgesics for neuropathic pain management. This scoping review aims to provide an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The inclusion criteria were original articles on PNP in rodent models that explored the use of compounds directly targeting cholinergic neurotransmission and reported results of nociceptive behavioral assays. The literature search was performed in the PubMed and Web of Science databases (1 January 2000–22 April 2023). The selection process yielded 82 publications, encompassing 62 compounds. The most studied compounds were agonists of α4β2 nAChR and α7 nAChR, and antagonists of α9/α10 nAChR, along with those increasing acetylcholine and targeting mAChRs. Studies mainly reported antinociceptive effects in traumatic PNP models, and to a lesser extent, chemotherapy-induced neuropathy or diabetic models. These preclinical studies underscore the considerable potential of cholinergic compounds in the management of PNP, warranting the initiation of clinical trials.

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Enhanced analgesic cholinergic tone in the spinal cord in a mouse model of neuropathic pain

Cited by 10 publications

References 63 publications

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

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

The efficacy of duloxetine depends on spinal cholinergic plasticity in neuropathic pain model rats

Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies

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