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      Effects of administration of α 2 adrenergic receptor agonist into psoas major muscle on inflammatory pain induced by injection of complete Freund’s adjuvant in rats

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          Abstract

          α 2 adrenergic agonists are widely used in clinical anesthesia and ICU sedation owing to their effective sedative and analgesic effects. Lumbago and leg pain is the most common clinical pain disease. Studies have reported that lumbago and leg pain is associated with dysregulation of paravertebral muscles, especially psoas major muscles. In the present study, a unilateral lower extremity chronic inflammation and pain model was established by subcutaneous administration of low-dose complete Fredrin’s adjuvant (CFA) into the posterior paw of rats. α 2 adrenalin receptor agonist was then injected into the psoas major muscle. Behavioral tests were conducted for 21 days. Psoas major muscle tissue was harvested for evaluation of biochemical indexes related to pain. The effect of α 2 adrenergic receptor agonist injected into psoas major muscle on chronic inflammatory pain of lower extremities in rats was explored. The results showed that injection of α 2 adrenergic receptor agonist into the psoas major muscle relieved CFA-induced mechanical hyperalgesia. Administration of α 2 adrenergic receptor antagonist yohimbine reversed the analgesic effect of α 2 adrenergic receptor agonists. Administration of dexmedetomidine into psoas major muscle downregulated the levels of norepinephrine, interleukin-6 and tumor necrosis factor-α in tissues. The findings of the present study show that administration of α 2 adrenoceptor agonists into the psoas major muscle relieves chronic inflammatory pain induced by CFA. Local injection of dexmedetomidine also exerted anti-inflammatory and anti-sympathetic effect by activating α 2-adrenoceptor in the psoas major muscle.

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          Most cited references41

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          Free radicals and antioxidants in normal physiological functions and human disease.

          Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
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            Correlation between the MRI changes in the lumbar multifidus muscles and leg pain.

            In the assessment of the lumbar spine by magnetic resonance imaging (MRI), changes in the paraspinal muscles are frequently overlooked. In this study, our objective was to investigate the relationships between lumbar multifidus (MF) muscle atrophy and low back pain (LBP), leg pain and intevertebral disc degeneration. A retrospective study of 78 patients (aged 17-72) with LBP presenting with back pain with or without associated leg pain was undertaken. Their MR images were visually analysed for signs of lumbar MF muscle atrophy, disc degeneration and nerve root compression. The clinical history in each case was obtained from their case notes and pain drawing charts. MF muscle atrophy was present in 80% of the patients with LBP. The correlation between MF muscle atrophy and leg pain was found to be significant (P < 0.01). However, the relationships between muscle atrophy and radiculopathy symptoms, nerve root compression, herniated nucleus pulposus and number of degenerated discs were statistically not significant. Examination of the paraspinal muscles looking for atrophy of MF muscle should be considered when assessing MR images of lumbar spine. This may explain the referred leg pain in the absence of other MR abnormalities. Copyright 2000 The Royal College of Radiologists.
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              CT imaging of trunk muscles in chronic low back pain patients and healthy control subjects.

              Increasing documentation on the size and appearance of muscles in the lumbar spine of low back pain (LBP) patients is available in the literature. However, a comparative study between unoperated chronic low back pain (CLBP) patients and matched (age, gender, physical activity, height and weight) healthy controls with regard to muscle cross-sectional area (CSA) and the amount of fat deposits at different levels has never been undertaken. Moreover, since a recent focus in the physiotherapy management of patients with LBP has been the specific training of the stabilizing muscles, there is a need for quantifying and qualifying the multifidus. A comparative study between unoperated CLBP patients and matched control subjects was conducted. Twenty-three healthy volunteers and 32 patients were studied. The muscle and fat CSAs were derived from standard computed tomography (CT) images at three different levels, using computerized image analysis techniques. The muscles studied were: the total paraspinal muscle mass, the isolated multifidus and the psoas. The results showed that only the CSA of the multifidus and only at the lowest level (lower end-plate of L4) was found to be statistically smaller in LBP patients. As regards amount of fat, in none of the three studied muscles was a significant difference found between the two groups. An aetiological relationship between atrophy of the multifidus and the occurrence of LBP can not be ruled out as a possible explanation. Alternatively, atrophy may be the consequence of LBP: after the onset of pain and possible long-loop inhibition of the multifidus a combination of reflex inhibition and substitution patterns of the trunk muscles may work together and could cause a selective atrophy of the multifidus. Since this muscle is considered important for lumbar segmental stability, the phenomenon of atrophy may be a reason for the high recurrence rate of LBP.
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                Author and article information

                Journal
                Mol Pain
                Mol Pain
                spmpx
                MPX
                Molecular Pain
                SAGE Publications (Sage CA: Los Angeles, CA )
                1744-8069
                2022
                4 August 2022
                : 18
                : 17448069221107810
                Affiliations
                [1 ]Division of Anesthesiology, Department of Cardiovascular Surgery, universityGuangdong Institute of Cardiovascular; , Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
                [2 ]Department of Anesthesiology, universityGuangdong Provincial People’s Hospital; , (Zhuhai Golden Bay Center Hospital), Zhuhai, China
                [3 ]Department of Anesthesiology, universityGuangdong Provincial People’s Hospital; , Guangdong Academy of Medical Sciences, Guangzhou, China
                Author notes
                [*]Jiexian Liang, Division of Anesthesiology, Department of Cardiovascular Surgery, Guangdong Institute of Cardiovascular, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 96 DongChun Road, Guangzhou, Guangdong 510080, China. Email: lijessy@ 123456msn.com
                [*]Qingshi Zeng, Department of Anesthesiology, Guangdong Provincial People’s Hospital Zhuhai Hospital (Zhuhai Golden Bay Center Hospital), Zhuhai 519040, China. Email: 1963088488@ 123456qq.com
                Author information
                https://orcid.org/0000-0002-0937-4880
                https://orcid.org/0000-0002-9612-4598
                Article
                10.1177_17448069221107810
                10.1177/17448069221107810
                9358342
                35658695
                5f5bead4-b9cb-4160-80b8-f59fd149d49a
                © The Author(s) 2022

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 23 April 2022
                : 24 May 2022
                : 31 May 2022
                Funding
                Funded by: National Natural Science Foundation of China, FundRef https://doi.org/10.13039/501100001809;
                Award ID: 81171040 and 81371236
                Categories
                Research Article
                Custom metadata
                ts10
                January-December 2022

                Molecular medicine
                lumbago and leg pain,psoas major,α2 adrenergic receptor,complete freund’s adjuvant,inflammatory pain

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