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      Alpha lipoic acid attenuates evoked and spontaneous pain following surgical skin incision in rats

      research-article
      a , a , a , a , b
      Channels
      Taylor & Francis
      Postsurgical pain, T-type calcium channel, acute pain, Alpha lipoic acid, novel analgesics

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          ABSTRACT

          Our previous studies have implicated Ca V3.2 isoform of T-type Ca2+ channels (T-channels) in the development of postsurgical pain. We have also previously established that different T-channel antagonists can alleviate in vivo postsurgical pain. Here we investigated the analgesic potential of another T-channel blocker and endogenous antioxidant molecule, α-lipoic acid (ALA), in a postsurgical pain model in rats. Our in vivo results suggest that single and repetitive intraperitoneal injections of ALA after surgery or preemptively, significantly reduced evoked mechanical hyperalgesia following surgical paw incision. Furthermore, repeated preemptive systemic injections of ALA effectively alleviated spontaneous postsurgical pain as determined by dynamic weight-bearing testing. We expect that our preclinical study may lead to further investigation of analgesic properties and mechanisms of analgesic action of ALA in patients undergoing surgery.

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          Most cited references47

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          Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers.

          This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al., 2015) and is intended to provide the rubric for peer review. Thus, it is directed towards authors, reviewers and editors. Explanations for many of the requirements were outlined previously and are not restated here. The new guidelines are intended to replace those published previously. The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards.
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            Persistent postsurgical pain: risk factors and prevention.

            Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem. Iatrogenic neuropathic pain is probably the most important cause of long-term postsurgical pain. Consequently, surgical techniques that avoid nerve damage should be applied whenever possible. Also, the effect of aggressive, early therapy for postoperative pain should be investigated, since the intensity of acute postoperative pain correlates with the risk of developing a persistent pain state. Finally, the role of genetic factors should be studied, since only a proportion of patients with intraoperative nerve damage develop chronic pain. Based on information about the molecular mechanisms that affect changes to the peripheral and central nervous system in neuropathic pain, several opportunities exist for multimodal pharmacological intervention. Here, we outline strategies for identification of patients at risk and for prevention and possible treatment of this important entity of chronic pain.
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              Characterization of a rat model of incisional pain.

              In this study, we developed a rat model of incisional pain. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in halothane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at different areas around the wound before surgery and for the next 6 days. A cumulative pain score based on the weight bearing behavior of the animals was also utilized. The results of tests for withdrawal responses and scores based on weight bearing suggest that a surgical incision of the rat foot causes a reliable and quantifiable mechanical hyperalgesia lasting for several days after surgery. An incision that only included skin and fascia but not muscle in the foot caused less severe hyperalgesia during the initial postoperative period. Distinct areas around the wound had different withdrawal thresholds during the study period. Even remote sites as much as 10 mm from the wound showed persistent mechanical hyperalgesia. Selective denervations of the rat hindpaw prior to foot incision revealed both the sural and tibial nerves were responsible for transmitting input from the incision that produces hyperalgesia. This model should allow us to understand mechanisms of sensitization caused by surgery and investigate new therapies for postoperative pain in humans.
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                Author and article information

                Journal
                Channels (Austin)
                Channels (Austin)
                Channels
                Taylor & Francis
                1933-6950
                1933-6969
                12 April 2021
                2021
                12 April 2021
                : 15
                : 1
                : 398-407
                Affiliations
                [a ]Department of Anesthesiology, University of Colorado Denver Anschutz Medical Campus; , Aurora, CO, USA
                [b ]Neuroscience Graduate Program, Graduate Program in Pharmacology, and Graduate Program in Biomedical Sciences, University of Colorado Denver, Anschutz Medical Campus and Rocky Mountain Regional VA Medical Center; , Aurora, CO, USA
                Author notes
                Author information
                https://orcid.org/0000-0003-2613-0391
                Article
                1907058
                10.1080/19336950.2021.1907058
                8043189
                33843451
                1a1791cf-5835-425a-827f-4217b518f083
                © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 5, References: 47, Pages: 10
                Categories
                Research Article
                Research Paper

                Molecular biology
                postsurgical pain,t-type calcium channel,acute pain,alpha lipoic acid,novel analgesics

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