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From joint degeneration to brain adaptation: Neuroplasticity in knee osteoarthritis
*Corresponding author: Soundararajan Kannan, Department of Physiotherapy, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India. k.soundararajan1995@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Suresh S, Kannan S, Antony Leo Aseer P, Subbiah K. From joint degeneration to brain adaptation: Neuroplasticity in knee osteoarthritis. Adesh Univ J Med Sci Res. doi: 10.25259/AUJMSR_16_2025
Abstract
Knee osteoarthritis (KOA) is a chronic condition in which the knee joint progressively deteriorates, causing persistent pain and restrictions in mobility. Neuroplastic changes in the central nervous system, like the dorsolateral prefrontal cortex, periaqueductal gray, and ventral tegmental area, have an important role in the influence of maladaptive pain perception in KOA. Treatment with exercises like resisted exercises and aerobic exercises like Tai Chi, Baduanjin, and cycling enhances adaptive neuroplasticity by improving brain connectivity and motor control. Neuromodulation techniques, such as transcranial direct current stimulation and repetitive transcranial magnetic stimulation, along with electrical stimulation treatments like peripheral electrical stimulation and transcutaneous electrical nerve stimulation, aid these adaptations. Including neuroplasticity-focused rehabilitation techniques in KOA treatment is important for a full recovery.
Keywords
Exercise
Healthcare
Neuroplasticity
Osteoarthritis knee
Stimulation
INTRODUCTION
Knee osteoarthritis (KOA) is the most prevalent condition that keeps progressively degenerating and leads to pain, stiffness, and functional limitations in an individual. KOA is particularly prevalent among the elderly population. KOA accounts for more than 80% of the burden of the total osteoarthritis population.[1,2] Conventionally, KOA is seen as a localized joint disorder that is characterized by cartilage degradation, synovitis, and osteophyte formation, but KOA has been evident to have both structural and functional changes in the nervous system of an affected individual that limit them.[1] These changes are called neuroplasticity; in this phenomenon, the brain can reorganize and adapt in response to pain and dysfunction; this plays a vital part in the persistence of pain in KOA. The pain pathway in KOA involves key components of the central nervous system (CNS). The descending opioid signaling pathway is central to pain regulation, with the periaqueductal gray (PAG) being the critical region. Patients experiencing greater pain tend to have increased opioid receptor activity in the PAG. The PAG gets signals from the anterior cingulate cortex (ACC) and prefrontal cortex and sends signals to the rostral ventromedial medulla, which connects to the spinal cord to help manage pain.[3] Another crucial system is the dopamine rewarding system, which affects the motivation and pain relief of a patient. Recent studies have explored how KOA affects not only the physical symptoms but also the person’s brain activity, highlighting the brain’s role in pain perception and modulation of pain. Various exercise interventions have been shown to alleviate the pain in KOA patients while modulating the brain’s functions.[3] Some studies have explored the effectiveness of combining two exercises, transcranial direct current stimulation (tDCS) and intramuscular electrical stimulation (EIMS); these interventions help in the treatment of KOA by involving the motor cortex and other pain-modulatory regions.[1-6]
METHODOLOGY
This narrative review was done in the following defined format. The study was registered in the open sciences framework. The PICOT(S) method proposed by Swanson et al.[7] was used in this study to formulate a search strategy.
P (population) - People who are diagnosed with KOA.
I (intervention) - Physiotherapy-based interventions (exercise therapy, manual therapy, uses of modalities)
C (comparison) - No treatment or other interventions (pharmacological, education, surgery)
O (outcome) - Clinical outcomes like pain reduction, functional mobility, quality of life enhancement, and other neuroplasticity-related outcomes (cortical remapping, motor control improvement)
T (time) - From Inception to February 2025
S (study design) – Only randomized controlled trials (RCTs) related to neuroplasticity and KOA within the past 10 years were included.
This narrative review analyzed a wide range of topics by reviewing RCTs from the past 10 years. Relevant articles were found by searching databases including PubMed, Medline, Research Gate, and Web of Science, originally using the Medical Subject Headings (MeSH) terms “knee osteoarthritis” and “neuroplasticity.” To ensure the relevance and precision of our search results, we opted to use MeSH terms, specifically “neuroplasticity” and “knee osteoarthritis,” instead of relying on the author’s keywords. This decision was intentional, as MeSH terms are systematically assigned by database specialists and act as more robust indicators of the content, thereby enhancing the accuracy of our search. Boolean operators (AND, OR) were used to refine the search results. Restrictions were placed on the year of publication (Articles from the past 10 years were reviewed) to ensure an advanced review of the literature.
The review included the population of people with KOA, Articles with Interventions focusing on the conservative management of KOA, and articles associated with neuroplasticity and KOA. Restrictions were placed on the study design; only RCTs were reviewed, and articles published in English were included.
Studies were excluded if they focused on non-human populations, discussed unrelated interventions (e.g., Surgical interventions), or did not address KOA about the selected factors.
We deleted doubles after checking the abstracts of the remaining articles. Finally, we analyzed the subset of 10 articles. Since this is a review of existing literature, no ethical approval was required. All included studies were credited appropriately. The characteristics of the included studies in this narrative review are shown in Figure 1 and Table 1.
- Flowchart of the study selection process. RCT: Randomized controlled trial
| Authors’ | Study design | Sample size | Intervention | Limitations | Highlights |
|---|---|---|---|---|---|
| Da Graca- Tarragó et al.[1] | Randomized controlled trail | In this study, a total of 60 women with KOA aged 50–75 participated. There are no men mentioned in the sample size provided in the text. Outcome measure: 1. Primary outcome: Visual analog scale, descending pain modulatory, secondary. 2. Outcome: Pain pressure threshold, disability due to pain. |
1. Active tDCS and active EIMS. 2. Sham (placebo) tDCS and Sham EIMS. 3. A ctive tDCS and sham EIMS. 4. Sham tDCS and Active EIMS. |
1. Gender-specific sample: The study includes only women. 2. Limited no.of. sessions: Although the study found immediate pain relief, more sessions may be needed to produce long-lasting effects. 3. Lack of long-term outcome: The study does not evaluate the long-term effect of clinical impact of the combined therapies. |
This study concludes that combining trans-cranial direct current stimulation with intramuscular electrical stimulation is highly effective in reducing pain, improving disability, and enhancing pain modulation in women with knee osteoarthritis than using either intervention alone or sham treatments. |
| Liu et al.[2] | Randomised controlled trail | A total of 140 patients with KOA. Participants were in the average age group of 54–60 years. Of the 140 participants, 38 were male and 102 were female. 1. Outcome measure: Knee injury and osteoarthritis. 2. Outcome score (KOOS), resting state functional magnetic resonance imaging, structural MRI to evaluate gray matter volume changes, serum biomarkers including programmed cell death protein 1 (PD- 1). |
1. Tai Chi. 2. Baduanjin. 3. Stationary cycling. 4. Health education (Control group): Participants received health education related to KOA but did not participate in any physical or mindfulness exercises. All interventions were conducted within 12 weeks. |
1. Short duration: The 12-week treatment period may not be enough to evaluate the extended effects of the exercises on KOA pain and brain function. 2. Small sample size: A higher sample size is needed to validate the findings and improve generalizability. |
The study concluded that Tai Chi, BDJ, and stationary cycling significantly reduced pain and modulated brain activity in KOA patients. These exercises altered DLPFC-SMA connectivity and were linked to changes in serum biomarkers. The findings suggest that both physical and mind–body exercises can effectively manage KOA pain and emphasize the potential of neuroimaging biomarkers in predicting treatment responses. |
| Liu et al.[3] | Randomized controlled trial | This study consists of 140 members who have KOA. However, the gender distribution and specific age group of the participants are not mentioned. 1. Outcome measure: KOOS, fMRI and structural MRI, PD-1. |
The interventions in this study involved three different exercise modalities and a control group, each conducted over 12 weeks: 1. Tai Chi. 2. BDJ. 3. Stationary cycling 4. Health education (Control group): This group received general health education but did not participate in any structured physical activity. Health education interventions typically include guidance on managing osteoarthritis, information on physical activity, diet, and pain management techniques. |
1. Short duration: A 12-week intervention duration might not be long enough to capture the long-term uses of the different exercise modalities on KOA symptoms and brain connectivity. 2. Lack of blinding: Participants were aware of the exercise group they were assigned to, which may introduce bias in self-reported outcomes like the KOOS pain sub-score. |
The study concluded that Tai Chi, BDJ, and stationary cycling significantly reduced pain and inflammation in KOA patients. These exercises modulated brain connectivity in areas linked to pain perception and motivation, suggesting that physical activity positively impacts both physical symptoms and emotional well-being. The findings signify the potential of exercise-based treatments for controlling chronic pain in osteoarthritis. |
| Soriano- Maldonado et al.[4] |
Randomized controlled trial | The study had 100 people participating with clinical and radiographic KOA, who were randomly put into two groups: 50 participants received a corticosteroid injection, and 50 participants received a placebo (saline) injection. Out of these, 45 and 44 participants completed the trial, respectively. The outcome measures were: 1. Pressure-pain sensitivity. 2. Temporal summation. |
1. Corticosteroid injection Group. 2. Placebo injection group. exercise-based intervention program: 14 days after getting the injections, all participants, regardless of group, underwent a 12- week supervised exercise program. The specifics of the exercise regimen were not detailed in the abstract but would typically include strengthening, flexibility, and aerobic exercises aimed at improving knee function and reducing OA symptoms. |
1. Corticosteroid dosage: The dose of corticosteroid (40 mg/mL) was moderate-range for knee joints and selected based on standard practice at the institution. It is unclear whether a higher or lower dose might have produced different results. 2. Timing of the exercise program: The exercise program started 2 weeks after the corticosteroid injection, which might have missed the optimal window of effectiveness for corticosteroids. |
The study concluded that administering a corticosteroid injection 14 days prior to starting an exercise program did not increase the pain sensitivity reduction in patients with KOA in comparison to a placebo. Both treatments showed similar effects, indicating no additional benefit from the steroid. |
| Pratscher et al.[5] |
Randomized controlled trial | The sample size for the pilot randomized controlled trial was 32 adults between the age group of 50–85 years with persistent knee pain lasting 3 months or longer. Participants were divided into groups for interventions involving intermittent fasting and glucose administration combined with a recognized pain treatment activity. The outcome measures included: 1. Feasibility: Evaluating the ability to recruit. |
1. Intermittent fasting. 2. Administration of glucose. 3. Pain treatment activity. |
1. Session length: The first session took about 4 h to complete. 2. Equipment accessibility: There were times when the EEG equipment was not available, making it difficult to recruit and run participants. |
The pilot study found that intermittent fasting and glucose administration are practical and well- received interventions for older adults experiencing chronic knee pain. Participants showed openness to participating in extended interventions, and the methods employed effectively measured pain and brain function. |
| Luz-Santos et al.[6] |
Randomized controlled trial | The sample size for the study investigating the effects of neuromodulator techniques in individuals with KOA was 80 patients. These participants were randomized into four subgroups, with each group consisting of 20 individuals. The outcome measures included: 1. Primary outcomes: VAS. Western Ontario and McMaster Universities osteoarthritis index. |
1. Structured exercise program: All participants with KOA engaged in a land-based strengthening exercise module for five continuous days. The specifics of the exercise regimen were not detailed in the summary, but it typically involves exercises aimed at improving strength, flexibility, and overall function. 2. Neuromodulator techniques: Participants were randomized into four subgroups, each receiving different combinations of neuromodulator interventions prior to the exercise program for 20 min/day over the 5 days: Group 1: Active tDCS combined with sham PES. Group 2: Sham tDCS combined with active PES. Group 3: Both sham tDCS and sham PES. Group 4: Active tDCS combined with active PES. |
1. Lack of established protocols: The optimal parameters for combining exercise and neuromodulator techniques are not clearly defined, with ongoing debate about dosages and timing. 2. Limited evidence: While tDCS and PES show promise, the literature does not provide sufficient guidance on the most effective combinations or specific parameters for achieving the best outcomes. 3. Measurement limitations: The methods used to assess changes in cortical activity may not fully capture the extent of neurological reorganization or its impact on muscle function. 4. Short duration: The 5-day intervention may be too brief to observe significant long-term changes in pain, function, or cortical reorganization. 5. Single location: Conducting the study at one location limits the diversity of the patient population and may affect the generalizability of the results. |
The study indicates that integrating exercise with neuromodulator techniques such as tDCS and PES may improve treatment outcomes for KOA by positively affecting motor cortex activity. Nevertheless, additional research is necessary to determine the best protocols and to validate the effectiveness of these combined interventions across varied patient populations and over extended durations. |
| Lai et al.[8] | Randomized controlled trial | The study involves 148 participants with KOA, who were randomized to one of four subgroups for intervention. Outcome measures the primary outcome measures include: 1.VAS. 2. I sokinetic knee muscle strength to evaluate muscle performance. 3. KOOS 4. 36-item short-form health survey (SF-36). |
1. Quadriceps strength training: Participants will take part in a structured strengthening program targeting the quadriceps muscle, carried out 5 days a week for 12 weeks. 2. High-frequency rTMS: Participants in the relevant groups will receive high-frequency rTMS sessions, aimed at enhancing functional connectivity in the brain and addressing maladaptive plasticity. 3. Combination groups:There are groups that will receive both quadriceps strength training and high-frequency rTMS together, while others will receive sham rTMS along with strength training. 4. Control group: One group will receive sham rTMS and quadriceps strength training to serve as a comparative baseline for evaluating the effects of the actual rTMS. These interventions will be conducted over a 12-week period, with assessments taking place at points throughout the study to evaluate their effectiveness on pain and function in individuals with KOA multiple (KOA) |
1. Blinding issues: Participants and operators cannot be blinded due to the visible nature of the quadriceps strength training, potentially introducing detection bias. 2. Focus on quadriceps: The intervention focuses solely on quadriceps strengthening rather than the entire kinetic chain, which may limit overall rehabilitation benefits. 3. Strict exclusion criteria: While ensuring accuracy and validity of results, the strict exclusion criteria might limit the generalizability of findings to a wider KOA population. |
The conclusion for the study is that it aims to provide evidence on the combined effects of high-frequency rTMS combined with quadriceps strength training for treating KOA. The study seeks to determine whether this combination can lead to greater improvements in pain relief and muscle strength compared to quadriceps training alone. |
| Riis et al.[9] | Randomized controlled trial | Sample size: The study randomized 100 participants, with 50 in each group (corticosteroid and saline groups). Of these, 91 members who participated had complete MRI data at baseline assessment. Outcome measures: 1. Primary outcomes: KOOS. |
1.Intra-articular injection: Participants got either an intra-articular corticosteroid injection or a placebo injection (isotonic saline) into the knee joint. The injections were administered before starting the exercise therapy. 2. Exercise program: Following the injection, all participants underwent a structured exercise therapy program. The exercise program was designed to improve knee function and alleviate clinical symptoms of KOA. The duration of the exercise therapy was 14 weeks, with follow-up at week 26. |
1. No statistically important differences were found between corticosteroid and saline injections in MRI measures of synovitis. 2. The study was unable to explain improvements in pain and function based on MRI results. 3. The improvement in KAO symptoms could not be directly linked to changes in synovitis. |
The study found no evidence to support using intra-articular corticosteroids over saline in combination with an exercise program to reduce synovitis in KOA. Pain and function improvements were not associated with synovitis reduction on MRI, indicating that other mechanisms may contribute to symptom relief. |
| Henriksen et al.[10] |
Randomized controlled trial | The study randomized 100 participants into two groups, with 50 patients receiving an intra-articular corticosteroid injection and 50 receiving a placebo injection. Out of these, 45 members who participated in the corticosteroid group and 44 members in the placebo group completed the trial. Outcome measure: The primary outcome was the KOOS. |
1. Corticosteroid group: Received an intra-articular injection of methylprednisolone acetate, dissolved in lidocaine hydrochloride. 2. Placebo group: Participants got an intra- articular injection of isotonic saline mixed with lidocaine hydrochloride. Exercise program: 14 days after receiving the injections, both groups began a 12-week supervised exercise therapy program designed to improve knee function and alleviate symptoms of osteoarthritis. |
1. Low corticosteroid dosage may have impacted results. 2. Lidocaine in both groups could have masked corticosteroid effects. 3. Participant expectations may have overshadowed treatment effects. 4. No observed short-term benefits, even in cases with inflammation. |
The study found no additional clinical benefit from adding of methylprednisolone acetate to an intra- articular injection of saline and lidocaine prior to exercise in patients with KOA. Both treatment groups showed comparable improvements in pain and function. |
| Özgül Öztürk et al.[16] | Randomized controlled trial | A sample size of 36 members with KOA randomly split into two groups: 18 patients into the treatment receiving group like action observation therapy in addition to exercise and 18 in the control group receiving exercise alone. The primary outcome measures were pain severity and pressure pain threshold. |
The interventions in the study were conducted 3 times weekly for 6 weeks. 1. Treatment group: Patients received action observation therapy in addition to an exercise program. 2. Control group: Patients received exercise alone. Both groups followed their respective interventions under supervision for the same duration and frequency. |
1. Small sample size: The study had only 36 participants, which might limit the generalizability of the findings. 2. Short intervention duration: The intervention period was 6 weeks, which may not have been long enough to observe important differences between the groups. |
The study concluded that adding action observation therapy to an exercise program didn’t provide any extra benefits for improving pain, pressure pain threshold, Kinesio phobia, pain catastrophizing, or functionality in people with chronic knee pain from osteoarthritis. While both groups showed significant improvements, the results suggest that AOT may not enhance outcomes beyond exercise alone. |
KOA: Knee osteoarthritis, tDCS: Transcranial direct current stimulation, BDJ: Baduanjin, DLPFC: Dorsolateral prefrontal cortex, SMA: Supplementary motor area, MRI: Magnetic resonance imaging, fMRI: Functional magnetic resonance imaging, OA: Osteoarthritis, EEG: Electroencephalography, PES: Peripheral electrical stimulation, rTMS: Repetitive transcranial magnetic stimulation, Ts: Temporal summation, WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index, EIMS: Intramuscular electrical stimulation, KOOS: Knee injury and osteoarthritis outcome score, VAS: Visual analog scale
This methodology ensures a broad exploration of the topic while identifying key areas for further research.
RESULTS
Exercise interventions focusing on neuroplasticity in KOA demonstrate substantial benefits in regulating pain and motor function. Exercise therapy, including resistance training, aerobic exercises (Tai Chi, Baduanjin [BDJ], cycling), and quadriceps strengthening, enhances functional connectivity in pain-perceiving areas like the dorsolateral prefrontal cortex (DLPFC), ACC, and supplementary motor area (SMA), leading to reducing pain and enhancing motor control. Electrical stimulation methods such as transcutaneous electrical nerve stimulation (TENS), peripheral electrical stimulation (PES), and EIMS contribute to cortical reorganization and descending pain inhibition. Along with it, noninvasive brain stimulation (repetitive transcranial magnetic stimulation [rTMS]) enhances neuroplastic adaptation, especially when combined with exercise.
DISCUSSION
Many studies have been conducted, but only limited exploration has been made of the neuroplastic changes that occur in an individual with KOA. Such articles that focus on the neuroplastic effects of KOA have been picked in this narrative review. Chronic pain in KOA patients is a major public health issue in many nations, affecting physical capacity and well-being. The neuroplastic changes in KOA contribute to persistent pain, central sensitization, and impaired pain perception.[8-16] This narrative review explores the neuroplastic changes in KOA, analyzing the mechanism of altered pain perception and the effects of various physiotherapy interventions such as exercises, electrical stimulation, and neuromodulation.
Mechanism of neuroplasticity in KOA- understanding central pain processing
The idea of pain in KOA has developed from considering it as a nociceptive framework to the concept of central sensitization and altered pain modulation.[11,12] Mease et al. (2011)[11] Discuss the part of the centralized pain mechanism in osteoarthritis, giving more importance to the changes that take place in the CNS, more specifically the prefrontal cortex, PAG, ventral tegmental area, contribute to the chronic pain despite the peripheral joint degeneration. This centralization of pain shows maladaptive neuroplasticity, where persistent pain inputs reinforce dysfunctional cortical and subcortical connections. Arendt-Nielsen (2017)[12] further explained that pain sensitization in KOA, stating that increased responsiveness of the nervous system to the stimuli, decreased descending inhibitory control, and heightened activities in the areas that are responsible for pain perception and processing, including the DLPFC and the insular cortex. This sensitization causes pain to become chronic in such a way that even a mild stimulus can cause major discomfort.
Peripheral sensitization occurs because of enhanced nociceptor activity because of the inflammatory mediators from damaged joint tissues. This causes a decreased pain threshold, resulting in the patient becoming more sensitive to normally nonpainful stimuli.[11]
Exercise-induced neuroplasticity - rewiring the pain network
Many studies have explored the neuroplastic effects of various exercise modalities in KOA-associated pain. Liu et al. (2019)[2] and Liu et al. (2019)[3] used a multimodal magnetic resonance imaging technique to show that exercise-induced neuroplasticity plays an important part in pain modulation. They discovered that aerobic exercises, resistance training, and mindful movements like Tai Chi modified the functional capacity of the DLPFC, PAG, and ventral tegmental area, improving descending pain inhibition and decreasing central sensitization. These findings emphasize the importance of targeted exercise interventions in rewiring the maladaptive pain networks. Dantas et al. (2021).[13] Suggested that by recommending structured exercise programs can be used not only for improving musculoskeletal function but also to cause neuroplasticity adaptation that decreases pain perception. These findings coincide with the findings of Soriano-Maldonado et al. (2016),[4] In which the study was about the combined effect of intra-articular corticosteroids and exercise, showing a prominent reduction in pain related to altered neural activity in pain-associated cortical areas.
Lui et al. (2019)[2] The DLPFC resting state functional connectivity (rsFC) differences in four different exercise interventions. Tai Chi significantly decreased DLPFC rsFC with the bilateral SMA and increased DLPFC rsFC with the left ACC. BDJ significantly decreased DLPFC rsFC with the bilateral SMA and increased DLPFC rsFC with the left ACC. Stationary cycling significantly decreased DLPFC rsFC with the bilateral SMA and increased DLPFC rsFC with the left ACC. The BDJ group had significantly increased DLPFC rsFC with the left insula compared to the Tai Chi group and with the left hippocampus/amygdala compared to the stationary cycling group. Kindly refer Figure 2 for more information.
- The DLPFC rsFC change (post-intervention minus pre-intervention) differences among the four groups. A1-A2: Tai Chi significantly decreased DLPFC rsFC with the bilateral SMA (A1) and increased DLPFC rsFC with the left ACC (A2) compared to the control group (Tai Chi group n=28 and control group n=24). B1-B2: Baduanjin significantly decreased DLPFC rsFC with the bilateral SMA (B1) and increased DLPFC rsFC with the left ACC (B2) compared to the control group (Baduanjin group n=29 and control group n=24). C1-C2: Stationary cycling significantly decreased DLPFC rsFC with the bilateral SMA (C1) and increased DLPFC rsFC with the left ACC (C2) compared to the control group (cycling group n=27 and control group n=24). D. The Baduanjin group had significantly increased DLPFC rsFC with the left insula (D1, blue) compared to the Tai Chi group and with the left hippocampus/amygdala compared to the stationary cycling group (D1, red). Compared to the Baduanjin group, the Tai Chi group had significantly increased DLPFC rsFC with the mPFC (D2, yellow) (Tai Chi group n=28, Baduanjin group n=29, cycling group n=27). Exercise-induced neuroplastic changes. (Lui et al., 2019). Red: Baduanjin group Hippocampus/Amygdala. In the BDJ group, exercise-induced neuroplastic changes were observed in the hippocampus and amygdala (marked in red), regions primarily linked with memory consolidation, emotional regulation, and stress modulation. Blue: Baduanjin group → Left Insula. The BDJ group also showed changes in the left insula (marked in blue), an area involved in interoceptive awareness, emotional processing, and integrating bodily functions with cognitive processes. Yellow: Tai Chi group → medial prefrontal cortex, SMA: Supplementary motor area, LACC: Left anterior cingulate cortex, R mPFC: Right medial prefrontal cortex, R: Right. These regions are responsible for social cognition, planning, coordinating, initiating voluntary motor actions, attention regulation, emotional processing, decision-making, and emotional regulation.
Blue: The BDJ group showed increased DLPFC rsFC with the left insula compared to Tai Chi.
Red: The BDJ group had increased DLPFC rsFC with the left hippocampus/amygdala compared to stationary cycling.
Yellow: The Tai Chi group had increased DLPFC rsFC with the medial prefrontal cortex compared to BDJ.
All three interventions (Tai Chi, BDJ, and cycling) decreased DLPFC rsFC with the bilateral SMA and increased it with the left ACC.
Electrical stimulation and neuroplasticity in KOA
Non-invasive neuromodulation techniques, like TENS and PES, have attained attention for their part in changing pain-associated neural circuits. Johnson et al. (2022)[14] and Gibson et al. (2019)[15] conducted systematic reviews showing that TENS can improve neuroplasticity by stimulating endogenous pain inhibitory pathways, specifically with the PAG and ACC. These effects are especially relevant for KOA, where impaired descending modulation contributes to continuous pain. LuzSantos et al. (2017)[6] expanded this concept by analyzing the additive effects of tDCS along with PES in KOA. Their study protocol emphasizes how dual modality electrical stimulation may together improve cortical activities, enhancing adaptive neuroplasticity and improving pain control. Likewise, Da Graca Tarragó et al. (2019)[1] explained that EIMS regulates motor cortex activity by improving the effects of descending inhibition in KOA patients.
Corticosteroid injection, neuroplasticity, and exercise therapy
Although corticosteroid injections are typically used for temporary pain reduction in KOA patients, their influence on neuroplasticity is in the area of interest. Henriksen et al. (2015)[10] and Riis et al. (2017)[9] investigated if corticosteroid injections, when combined with exercise therapy, could alter brain connectivity and pain perception. Their findings proposed that while corticosteroids give short-term pain relief, the long-term benefits are primarily due to exercise-induced neural adaptations. This suggests that it is important to combine both interventions to have an optimal neuroplastic recovery.
rTMS and KOA pain modular
Lai et al. (2024)[8] suggested that combining repeated transcranial magnetic stimulation with quadriceps strengthening in KOA patients gives a remarkable result. The study protocol advocates repeated transcranial magnetic stimulation, focusing on the motor and prefrontal cortices, that could improve the impact of exercise on pain relief by regulating cortical activities and connectivity in the pain processing network.
Neuroplastic responsiveness and chronic pain treatment
Pratscher et al. (2021)[5] present the concept of “enhanced neuroplastic responsiveness” in chronic pain management. Their study implies that treatments focusing on neuroplasticity, such as cognitive training, neuromodulation, and exercise, may maximize the pain intervention outcome by boosting adaptive neural reorganization. This study supports that KOA treatment should be more than just focusing on structural joint preservation and should include treatments that actively reshape pain processing circuits.
CONCLUSION
This study reviewed literature that emphasized the importance of neuroplasticity in the pathophysiology and management of KOA. The abnormal changes in the central pain network, including the DSPFC, PAG, and ventral tegmental area, contribute to chronic pain and decreased endogenous pain inhibition. Exercise, electrical stimulation, and neuromodulation techniques offer a potential pathway for reversing these changes by improving cortical activities, enhancing functional connectivity, and strengthening descending pain modulation pathways. Future studies should target enhancing combinatory approaches, combining physical rehabilitation with neuroplasticity-focused therapies, to give long-lasting pain reduction and functional enhancement in KOA patients.
Ethical approval:
Institutional review board approval is not required.
Declaration of patient consent:
Patient’s consent not required as there are no patients in this study.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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