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      Peripheral and Central Pathological Mechanisms of Chronic Low Back Pain: A Narrative Review

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          Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.

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          Most cited references 119

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          Role of cytokines in intervertebral disc degeneration: pain and disc content.

          Degeneration of the intervertebral discs (IVDs) is a major contributor to back, neck and radicular pain. IVD degeneration is characterized by increases in levels of the proinflammatory cytokines TNF, IL-1α, IL-1β, IL-6 and IL-17 secreted by the IVD cells; these cytokines promote extracellular matrix degradation, chemokine production and changes in IVD cell phenotype. The resulting imbalance in catabolic and anabolic responses leads to the degeneration of IVD tissues, as well as disc herniation and radicular pain. The release of chemokines from degenerating discs promotes the infiltration and activation of immune cells, further amplifying the inflammatory cascade. Leukocyte migration into the IVD is accompanied by the appearance of microvasculature tissue and nerve fibres. Furthermore, neurogenic factors, generated by both disc and immune cells, induce expression of pain-associated cation channels in the dorsal root ganglion. Depolarization of these ion channels is likely to promote discogenic and radicular pain, and reinforce the cytokine-mediated degenerative cascade. Taken together, an enhanced understanding of the contribution of cytokines and immune cells to these catabolic, angiogenic and nociceptive processes could provide new targets for the treatment of symptomatic disc disease. In this Review, the role of key inflammatory cytokines during each of the individual phases of degenerative disc disease, as well as the outcomes of major clinical studies aimed at blocking cytokine function, are discussed.
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            Non-specific low back pain.

            Non-specific low back pain affects people of all ages and is a leading contributor to disease burden worldwide. Management guidelines endorse triage to identify the rare cases of low back pain that are caused by medically serious pathology, and so require diagnostic work-up or specialist referral, or both. Because non-specific low back pain does not have a known pathoanatomical cause, treatment focuses on reducing pain and its consequences. Management consists of education and reassurance, analgesic medicines, non-pharmacological therapies, and timely review. The clinical course of low back pain is often favourable, thus many patients require little if any formal medical care. Two treatment strategies are currently used, a stepped approach beginning with more simple care that is progressed if the patient does not respond, and the use of simple risk prediction methods to individualise the amount and type of care provided. The overuse of imaging, opioids, and surgery remains a widespread problem.
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              Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits.

              Chronic pain conditions are associated with abnormalities in brain structure and function. Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies. How brain activity reorganizes with transition from acute to chronic pain has remained unexplored. Here we study this transition by examining brain activity for rating fluctuations of back pain magnitude. First we compared back pain-related brain activity between subjects who have had the condition for ∼2 months with no prior history of back pain for 1 year (early, acute/subacute back pain group, n = 94), to subjects who have lived with back pain for >10 years (chronic back pain group, n = 59). In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group, n = 19) and those in which the back pain persists (persistent acute/sub-acute back pain group, n = 20; based on a 20% decrease in intensity of back pain in 1 year). We report results in relation to meta-analytic probabilistic maps related to the terms pain, emotion, and reward (each map is based on >200 brain imaging studies, derived from neurosynth.org). We observed that brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry. The results demonstrate that brain representation for a constant percept, back pain, can undergo large-scale shifts in brain activity with the transition to chronic pain. These observations challenge long-standing theoretical concepts regarding brain and mind relationships, as well as provide important novel insights regarding definitions and mechanisms of chronic pain.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                27 May 2021
                : 14
                : 1483-1494
                [1 ]Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine , Tianjin, People’s Republic of China
                [2 ]School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine , Tianjin, 301617, People’s Republic of China
                [3 ]National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion , Tianjin, 300381, People’s Republic of China
                Author notes
                Correspondence: Zhifang Xu School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine , No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel +86-22-5959-6290Fax +86-22-2748-5189 Email xuzhifangmsn@hotmail.com
                Bo Chen School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine , No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of ChinaTel +86-22-5959-6290Fax +86-22-2748-5189 Email tjutcmchenbo@163.com
                © 2021 Li et al.

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