Chronic low back pain (CLBP) can have a certain degree of impact on the patient’s physical structure and function, daily activities, and social participation. In the modern medical model, CLBP pain is considered as a biopsychosocial syndrome. Functional impairments in CLBP pain patients involve three levels: biologically, it is mainly manifested as local pain, limited function, and reduced ability to perform daily activities; psychologically, it is manifested as fear of movement, catastrophizing thoughts about pain, anxiety, depression, and reduced self-efficacy; socially, it is manifested as impaired social functioning, work absenteeism, and overall reduction in quality of life (Tagliaferri et al., 2020). Behind these various functional impairments, changes in brain structure and function may be one of the important pathological mechanisms. Based on this, the rehabilitation goals for CLBP have also changed, shifting from excessive focus on pain management and improvement of back symptoms to targeting the central nervous system to improve the overall physical and mental functional impairments of patients. In recent years, people have become increasingly aware of the appearance of a series of functional impairments and the prolonged course of CLBP, which are closely related to neuroplasticity changes (Nijs et al., 2017). Therefore, inducing neuroplasticity changes through certain therapies may be a feasible measure to improve the overall rehabilitation effectiveness of CLBP. Exercise, as a traditional rehabilitation therapy, plays an important role in inducing neuroplasticity and promoting disease recovery (Johansson et al., 2020). Exercise has characteristics such as planning and organization, and it is a collection of repetitive physical activities aimed at maintaining or promoting physical health. Its impact on brain structure and function has attracted increasing attention. Based on the current relevant research, this paper firstly introduces in detail the theory and molecular mechanism of exercise-induced neuroplasticity, secondly proposes a new concept of exercise-targeted neuroplasticity for the treatment of CLBP and outlines its mechanism, and lastly puts forward the concept of central-peripheral rehabilitation treatment for CLBP and looks forward to the prospect of applying mind–body exercise in the rehabilitation treatment of CLBP.

Neuronal plasticity is the ability of the nervous system to respond to internal and external stimuli such as physiological changes, pathological injuries, and environmental changes. Its essence is the brain’s self-regulatory mechanism to cope with chronic stress, injuries, and other changes through structural and functional changes (Kourosh-Arami et al., 2021). Neuronal plasticity is an important foundation for the recovery of structure and function in the central nervous system after lesions (Chernikova et al., 2013). Neuronal plasticity can be divided into structural plasticity and functional plasticity. Structural plasticity involves functional brain area anatomical and morphological changes such as neurogenesis, synaptogenesis, angiogenesis, axonal or dendritic sprouting, etc. Functional plasticity refers to the changes in neural network function and the formation of new neural pathways (Dan, 2019). There was a belief that neuroplasticity is stronger during early individual development and gradually diminishes in adulthood. However, both theoretical and practical research have refuted this viewpoint. In fact, neuroplasticity exhibits stage-specific and modular differences. During human development, neuroplasticity is strongest; in adulthood, certain brain regions such as the sensory cortex experience a decrease in plasticity, but areas like the motor cortex, prefrontal cortex, and hippocampus maintain a high level of plasticity (Karni et al., 1995; Sarı and Lunghi, 2023).

As an important discovery in neuroscience, neuroplasticity is the fundamental basis for the survival and repair of the nervous system after injury. Influencing neuroplasticity through certain interventions to promote injury recovery and pathological compensation has become an important treatment concept. As mentioned earlier, certain brain regions always have a high level of neuroplasticity. Therefore, inducing plasticity changes through certain stimuli such as exercise, cognitive training, and environmental changes may have unexpected therapeutic effects (Innocenti, 2022). In recent years, treatment techniques based on the theory of neuroplasticity have emerged continuously. Among them, non-invasive brain stimulation techniques that target brain functional areas and regulate interhemispheric function are typical representatives (Braun and Wittenberg, 2021). Furthermore, as research deepens, exercise, as a non-pharmacological therapy, has also shown great potential in regulating cerebral vascular function, inducing neuroplasticity, and inhibiting neuroinflammation (Reddy et al., 2023). Exercise can have beneficial effects on brain structure and function. Exercise can regulate neural activity, promote the expression of neurotrophic factors, and facilitate signal transduction. The increased release of neurotrophic factors further promotes neuronal production, proliferation, and differentiation; increases synaptic formation, enhances neural conduction efficiency, and improves functional neural activity; stimulates angiogenesis, increases cerebral perfusion, and achieves beneficial changes in neural structure and function. Exercise also promotes positive changes in the structural morphology of the brain, activates relevant functional brain regions, and promotes adaptive behavioral changes (Zhao et al., 2020). In addition, exercise can increase cortico-spinal excitability and have a positive impact on functional connectivity, gray matter density, and white matter microstructure in the motor area (Nicolini et al., 2021). The theory of exercise-induced neuroplasticity is being mentioned and studied by an increasing number of experts and scholars. Recent clinical practice has shown that CLBP is characterized by a long course, abnormal nociceptive processing mechanisms, decreased motor control function, and secondary changes in related functional brain areas, which may be important neuroplasticity changes (Brumagne et al., 2019). Induced neuroplasticity changes may be the key to the rehabilitation treatment of CLBP and its various complications.

Brain-derived neurotrophic factor (BDNF) is a key protein involved in neuroplasticity events after exercise (Kaagman et al., 2024). BDNF is a widely studied neurotrophic factor that plays an important regulatory role in neuronal function and brain health (Jaberi and Fahnestock, 2023). As the most widely distributed neurotrophic factor, BDNF can promote neuroplasticity throughout the lifespan (Voigt et al., 2024). BDNF can promote the differentiation of neural stem cells into astrocytes and oligodendrocytes, making it a key factor in neuroglial development. BDNF plays an important role in the process of neurogenesis, neuron survival, proliferation, and differentiation. The main mechanism is that mature BDNF (mBDNF) can bind to the tropomyosin receptor kinase B (TrkB) receptor, activate signaling pathways such as mitogen-activated protein kinase (MAPK), phospholipase C-γ (PLC-γ), phosphatidylinositol 3-kinase (PI3K)/Akt enzyme (Akt, also known as protein kinase B), and then activate transcription factor cyclic adenosine monophosphate (cAMP) response element-binding protein, playing roles in anti-apoptosis and synthesis of cytoskeletal proteins (Palasz et al., 2020). Neuronal generation, differentiation, and development are more active in regions such as the hippocampus, cerebellum, and cerebral cortex, where BDNF plays an important role. BDNF regulates synaptic formation and growth and promotes synaptogenesis (Binder and Scharfman, 2004), while BDNF stimulates vascular endothelial growth factor transcription, which in turn is involved in neoangiogenesis (Lin et al., 2014). In addition, BDNF exhibits neuroprotective effects under adverse conditions such as glutamate excitotoxicity, neurotoxic stimulation, and cerebral ischemia. In addition, BDNF is also a key molecule in brain learning and memory, playing an important role in cognitive function and preventing neurodegenerative changes (Decker, 2023). Some scholars have suggested that physical exercise improves brain health by promoting neurogenesis and modulating neuroplasticity and that an important molecular mechanism is the increased expression of BDNF (Cefis et al., 2023). One research has found that long-term aerobic exercise can increase the concentration of BDNF, insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), and other factors. BDNF promotes neuroplasticity throughout the lifespan, IGF-1 is crucial for brain development and normal function maintenance, and VEGF promotes neural precursor proliferation (El-Sayes et al., 2019). A systematic review and network meta-analysis study showed that high-intensity interval training also induces neuroplastic changes in the brain by increasing BDNF levels (Rodríguez-Gutiérrez et al., 2024).

Another key signaling molecule that may be involved in exercise-induced neuroplasticity is lactate (Lei et al., 2024). In recent years, the role of lactate in brain development and functional maintenance, synaptic plasticity, and angiogenesis has attracted the attention of scholars (Wu et al., 2023). During exercise, muscles can produce lactate, which enters the bloodstream and crosses the blood–brain barrier through monocarboxylate transporters. Another source of lactate in the brain is glycolysis within astrocytes. Exercise causes an increase in neuronal metabolic demand, and a portion of the glycogen stored in astrocytes is degraded to lactate to maintain neuronal function (Akter et al., 2023). As the level of lactate in the brain increases sharply, the NADH/NAD+ ratio increases, leading to an increase in prostaglandin E2 and nitric oxide production, causing cerebral vasodilation and improving cerebral blood circulation. In addition, lactate can also induce neurovascular coupling through certain mechanisms, increase BDNF expression and synthesis, and mediate neuroplasticity. Research has shown that the increase in lactate levels after high-intensity exercise is related to the increase in BDNF levels (Müller et al., 2020). Lactate, as a signaling molecule, improves cerebral blood flow and increases the release of BDNF, which is a possible important mechanism for exercise-induced neuroplasticity. High-intensity interval training can increase lactate levels and improve cerebral vascular function through related signaling pathways, activating neuroplasticity (Huang et al., 2021). A Systematic Review showed that high-intensity interval training increased plasma concentrations of neuroplasticity markers such as lactate, BDNF, and VEGF in the brains of stroke patients and promoted functional recovery (Montero-Almagro et al., 2024). Another animal study showed that high-intensity intermittent training promoted hippocampal mitochondrial function and ameliorated neuronal synaptic dysfunction via the lactate receptor (GPR81)-ERK1/2 pathway, in which lactate plays a mediating role (Shang et al., 2023). In addition, aerobic exercise may also improve cortical inhibition function by elevating lactate levels, and one clinical study found that patients who produced higher lactate during aerobic exercise achieved faster response inhibition. In conclusion, lactate plays a role in the regulation of neuronal excitability and the induction of synaptic plasticity, In the future, the specific mechanisms of lactate in neural network regulation need to be further investigated (Griego and Galván, 2023). In summary, the molecular mechanisms of exercise-induced neuroplasticity are shown in Figure 1.

Neuroplasticity changes in patients with CLBP are an important mechanism leading to their physical and mental functional impairments (Figure 2). Under physiological conditions, neuroplasticity mechanisms ensure the normal development of life activities. Under the influence of pathological factors, changes in the central nervous system may have adverse effects on the body. Therefore, reversing the changes in brain structure and network activation or reorganization associated with pain behavior through certain means has become a new treatment approach (Medrano-Escalada et al., 2022). Currently, there are two ways to achieve this: one is from the central to the peripheral, including motor imagery, cognitive behavioral therapy, non-invasive brain stimulation techniques, etc., especially the combination of non-invasive brain stimulation techniques and pain neuroscience education (PNE) has become an important direction for future development. The other way is from the peripheral to the central, achieved through exercise, manual therapy, and stimulation of peripheral physical factors. Obviously, exercise induces neuroplastic changes through the latter pathway, thereby achieving corresponding rehabilitation effects. In recent years, mind–body exercise has been widely carried out, which implies the rehabilitation treatment concept of central-peripheral. Currently, traditional Chinese exercises such as qigong, yoga, and Pilates, which represent mind–body exercise, have been applied in the treatment of low back pain in clinical practice. Mind–body exercise is based on attentional focus, using mindfulness, meditation, guided imagery, etc., combined with gentle movements and breath control to enhance mind–body coordination and awareness, increase vitality, promote energy flow and release of endogenous neurohormones, activate self-regulation ability, and induce neuroplastic changes (Zou et al., 2017). In the future, the integration of physical and cognitive behavioral regulation in exercise may play a greater role in the rehabilitation treatment of CLBP, and its mechanism deserves further research and exploration.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

JZ: Writing – original draft. SH: Writing – review & editing.