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  • Systematic Review
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26 September 2025

19 Pages

Neurocognitive Interventions Informed by Cognitive–Behavioral Therapy (CBT) Principles and Physical Exercise for Complex Regional Pain Syndrome: A Systematic Review

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1
Physiotherapy Program, Department of Health, Universidad Santiago de Cali, Santiago de Cali 760035, Colombia
2
Carrera de Kinesiología, Escuela de Kinesiología, Facultad de Ciencias de la Rehabilitación y Calidad de Vida, Universidad San Sebastián, Lientur 1457, Concepción 4030000, Chile
3
Internal Medicine Specialization Program, Department of Health, Universidad Santiago de Cali, Santiago de Cali 760035, Colombia
4
Research and Education Group GIEDCO, Clínica de Occidente S.A., Santiago de Cali 760046, Colombia
J. Clin. Med.2025, 14(19), 6820;https://doi.org/10.3390/jcm14196820
This article belongs to the Special Issue Chronic Pain: Non-Pharmacological Treatments and Rehabilitation Strategies
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Abstract

Background: Complex Regional Pain Syndrome (CRPS) is a chronic pain condition that usually affects a limb following injury or surgery and is characterized by severe pain accompanied by sensory, motor, autonomic, and trophic disturbances. Methods: This systematic review aimed to synthesize the available evidence on the effectiveness of physical exercise and neurocognitive interventions grounded in cognitive–behavioral therapy (CBT) principles for the management of CRPS. A comprehensive search was conducted in Medline (via Ovid), LILACS, ScienceDirect, PEDro, OTseeker, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligible studies included clinical trials, cohort studies, and cross-sectional studies, whereas case reports, pediatric populations, and animal studies were excluded. Fifteen studies met the inclusion criteria. Results: The findings indicated that aerobic exercise was consistently associated with pain reduction and functional improvement. Neurocognitive interventions informed by CBT principles, such as mirror therapy and graded exposure, also demonstrated efficacy in decreasing pain and enhancing functional independence. Most studies supported the effectiveness of these approaches in the management of CRPS. Overall, both physical exercise and neurocognitive interventions grounded in CBT principles produced positive effects on pain modulation, physical function, and daily activity performance. Conclusions: These findings highlight the therapeutic potential of combining physical and psychologically informed interventions for the treatment of CRPS.

1. Introduction

Complex Regional Pain Syndrome (CRPS) is a chronic condition characterized by severe and persistent pain that may affect one or more extremities [1]. The worldwide incidence of CRPS is unknown; however, some epidemiological studies report an incidence rate ranging from 5.46 to 26.2 cases per 100,000 persons per year [2,3]. CRPS occurs most frequently in adults between 40 and 70 years of age; women are more affected than men at a ratio of 3:1, and in children, girls are more frequently affected than boys at a ratio of 9:1 [4]. In adults, the upper extremities are usually more affected than the lower extremities [5], whereas in children, the lower extremities are typically more affected than the upper extremities [6].
The pathogenesis of CRPS is multifactorial, most commonly associated with fractures or surgery, but it can also occur after spinal cord, nerve, or ligament injury, and in some cases spontaneously. Peripheral sensitization, autonomic nervous system dysregulation, and immune dysfunction are thought to contribute to the development of CRPS [7]. It is classified into two types: type I (reflex sympathetic dystrophy) occurs without confirmed peripheral nerve injury, and type II (causalgia) occurs in the presence of such injury [8]. The main symptoms include allodynia or hyperalgesia disproportionate to the precipitating event, as well as skin changes, sudomotor dysfunction, or edema [9].
The treatment of CRPS is multidisciplinary and includes pharmacological management, sympathetic nerve blocks, psychotherapy, occupational therapy, physiotherapy, and complementary therapies [10]. Among these strategies, clinical guidelines highlight physiotherapy as a key approach to controlling pain and disability. This includes therapeutic exercise and techniques based on neurocognitive rehabilitation (such as mirror therapy or graded motor imagery), which integrate cognitive and behavioral principles to address maladaptive pain perception and motor function [11,12,13]. While these are informed by psychological approaches, they do not constitute formal Cognitive–Behavioral Therapy (CBT) as delivered by mental health professionals.
CBT is a structured, time-limited intervention aimed at improving emotional and functional status by identifying and modifying maladaptive thoughts and behaviors [14]. Although traditionally based on techniques such as cognitive restructuring, thought records, and behavioral exposure, in the context of CRPS, complementary interventions have emerged. While not directly derived from CBT, these methods share cognitive and behavioral principles and are integrated into a comprehensive therapeutic approach. This review therefore also considers techniques such as mirror therapy [15], graded motor imagery [16,17], prism adaptation [18,19], virtual reality-mediated interventions [20], and pain exposure physical therapy [17,21], as well as any intervention grounded in cognitive–behavioral principles, due to their utility in modifying pain perception, movement patterns, and coping strategies.
Physical exercise, on the other hand, has proven to be an effective and safe therapeutic tool in the management of CRPS. Clinical guidelines recommend it as a fundamental component of the multimodal approach. Various studies indicate that interventions such as progressive mobilization, aerobic exercise, and aquatic therapy can help reduce pain, improve physical function, and decrease edema in patients with CRPS type I [22]. Although further research is needed to determine optimal protocols, current evidence strongly supports the inclusion of exercise as a key element of rehabilitation.
Despite the range of available interventions, evidence on the rehabilitative treatment of CRPS remains limited. It is still unclear which strategies are most effective in reducing pain and disability, or whether their combination with conventional therapies yields superior outcomes. Therefore, the purpose of this review is to examine the effectiveness of physical exercise and neurocognitive interventions informed by cognitive and behavioral principles in the treatment of patients with CRPS, in order to support evidence-based clinical decision-making.

2. Materials and Methods

This systematic review was conducted in accordance with the PRISMA 2020 guidelines [23], as detailed in the Supplementary Materials. The protocol was registered in the Prospective International Register of Systematic Reviews (PROSPERO) under registration number CRD4202020209914.

2.1. Selection Criteria

The following research question (RQ) was established:
  • Population: adult patients (≥18 years) diagnosed with complex regional pain syndrome.
  • Intervention: physical exercise and cognitive–behavioral interventions.
  • Comparison: Conventional therapy or usual care, including hydrotherapy, early stimulation (e.g., TENS), physical modalities, occupational therapy, and facilitation techniques, without neurocognitive elements.
  • Outcomes: Pain: Measured using the Numerical Rating Scale (NRS), Visual Analog Scale (VAS), or McGill Pain Questionnaire.; Physical function: Assessed through passive range of motion (via goniometry) and strength (using a hand dynamometer); and Functional Outcomes or Disability Related to Daily Activities: Evaluated using instruments such as the Patient-Rated Wrist/Hand Evaluation (PRWHE), QuickDASH, the 5-item version of the EQ-5D (EQ-5D-5L), the Oswestry Low Back Pain Disability Questionnaire, and the Roland-Morris Disability Questionnaire.
Included studies:
We included experimental, quasi-experimental, cohort, case–control, and cross-sectional designs involving adult patients diagnosed with CRPS type I or II, associated with neurological or musculoskeletal conditions.
Exclusion criteria:
We excluded case reports, studies involving pediatric populations or animal models, and research focused exclusively on pharmacological or surgical interventions without including physical exercise or cognitive–behavioral therapy.

2.2. Source of Information and Strategy Search

A comprehensive literature search was conducted using Medical Subject Headings (MeSH), DeCS terms, and related keywords. The following databases were searched from their inception to 31 December 2024: MEDLINE (via Ovid), ScienceDirect, LILACS, PEDro, OTseeker, and the Cochrane Central Register of Controlled Trials (CENTRAL). No language or publication date restrictions were applied. The search strategy included terms such as “Complex Regional Pain Syndromes”, “Physical Therapy”, “Cognitive-Behavioral Therapy”, “Physical Therapy Modalities”, “Exercise”, “Mirror Therapy”, “Motor Imagery”, “Range of Motion, Articular”, “Activities of Daily Living”, and “Motor Function”, applied to titles and abstracts. The complete search strategy is available in the PROSPERO protocol and detailed in Appendix A.

2.3. Selection of Articles

The study selection process began with a calibration phase to ensure consistency between reviewers during screening. References were managed using EndNote, and a manual filtering process was conducted in Microsoft Excel. Two reviewers independently screened titles and abstracts, followed by full-text review according to pre-defined inclusion and exclusion criteria. Disagreements were resolved through consensus; if unresolved, a third reviewer acted as arbiter. A pilot calibration phase was conducted to ensure consistency. Data were independently extracted from the included studies by the same reviewers using a standardized extraction form.

2.4. Process for Collecting Information

Two expert physiotherapist reviewers independently extracted data from each study using a standardized Excel matrix. The extracted information included study design, geographic location, authors and year of publication, title, objectives, methodology, sample size and participant age, CRPS type, inclusion and exclusion criteria, number of participants, description of the intervention and comparison groups, and outcomes related to pain and functional performance or disability in daily activities, along with the corresponding measurement instruments.

2.5. Article Quality Rating and Risk of Bias

The PEDro scale [24] was used to assess methodological quality of randomized controlled trials, and the MINORS tool was applied to non-randomized studies. The results of these evaluations were summarized narratively and visualized using figures that illustrate the fulfilment of each item from the PEDro and MINORS scales. High risk of bias related to allocation and blinding was noted across several studies and is discussed in the results and limitations.
For randomized trials, the PEDro scale evaluates criteria such as randomization, allocation concealment, baseline comparability, blinding of participants, therapists, and assessors, outcome data completeness (≥85% for at least one key outcome), intention-to-treat analysis, between-group statistical comparisons, and reporting of point estimates and measures of variability. Studies scoring 6 or higher on the PEDro scale were included in the review.
For observational and non-randomized studies, methodological quality and risk of bias were assessed independently and blindly using the MINORS (Methodological Index for Non-Randomized Studies) scale. This tool evaluates elements such as a clearly stated objective, inclusion of consecutive patients, prospective data collection, appropriate analysis, reporting of data loss, and baseline equivalence between groups. A minimum score of 11 on the MINORS scale [25] was required for study inclusion.

2.6. Data Analysis and Results Synthesis

Quantitative data were extracted for descriptive analysis. Due to the high heterogeneity in interventions (e.g., Mirror Therapy, GMI, Prism Adaptation) and outcomes, the results are synthesized narratively and grouped by type of intervention to aid interpretation. A meta-analysis was not conducted due to substantial clinical and methodological heterogeneity, as well as variability in the assessment methods, which prevented a reliable and objective synthesis of the results.

3. Results

3.1. Selection of Studies

The initial search identified a total of 606 studies. After removing duplicates, 317 studies were screened, and 34 were selected for full-text review. Nineteen studies were excluded because they involved treatment protocols unrelated to the intervention or outcome of interest (see Appendix B for a complete list of excluded studies and reasons). The remaining 15 studies were included in this review: Moseley et al., 2004 [26], Moseley et al., 2006 [27], Cacchio et al., 2009 [28], Lagueux et al., 2012 [29], Pervane et al., 2015 [30], Barnhoorn et al., 2015 [31], Topcuoglu et al., 2015 [32], Barnhoorn et al., 2015 [33], Christophe et al., 2016 [34], Hollander et al., 2016 [35], Schmid et al., 2017 [36], and Halicka et al., 2021 [19], Machač et al., 2024 [37], Lewis et al., 2021 [38], Saha et al., 2021 [39] (see Figure 1).
Figure 1. PRISMA 2020 flow diagram illustrating the study selection process, adapted from the official PRISMA template (www.prisma-statement.org accessed on 10 March 2025).

3.2. Characteristics of Excluded Studies

Excluded articles were not related to the intervention or outcome of interest. Additionally, letters to the editor, systematic reviews/narratives, pharmacologic intervention protocols, animal studies, and studies with pediatric populations were excluded.

3.3. Characteristics of the Included Studies

The 15 studies included in this review were published between 2004 and 2024. All studies included participants of both sexes, with sample sizes ranging from seven participants [29,34] to 56 participants [31]. Four studies evaluated interventions in stroke patients [28,30,32,39]. One study [26] focused on adults with wrist fractures, while the remaining studies did not specify the type of injury or the underlying causes associated with the occurrence of CRPS (Figure 2 and Figure 3).
Figure 2. Methodological quality assessment of randomized controlled trials using the PEDro scale. Green circles (+) indicate that the criterion was fulfilled, while red circles (−) indicate that it was not fulfilled. References: Moseley et al., 2004 [26]; Moseley et al., 2006 [27]; Cacchio et al., 2009 [28]; Pervane et al., 2015 [30]; Barnhoorn et al., 2015 [31]; Topcuoglu et al., 2015 [32]; Barnhoorn et al., 2015 [33]; Hollander et al., 2016 [35]; Schmid et al., 2017 [36]; Halicka et al., 2021 [19]; Machač et al., 2024 [37]; Lewis et al., 2021 [38]; Saha et al., 2021 [39].
Figure 3. Methodological quality assessment of non-randomized studies using the MINORS tool. Green circles (+) indicate that the criterion was fulfilled, while red circles (−) indicate that it was not fulfilled. References: Christophe et al., 2016 [34]; Lagueux et al., 2012 [29].
Regarding the condition evaluated, three studies included patients with CRPS affecting both upper and lower extremities [31,33,35]. Eleven studies exclusively involved patients with upper extremity CRPS, while only one study [34] included patients with both CRPS types (type I and II). Geographically, most studies were conducted in Europe (12/15), with the remaining studies conducted in North America (1/15), Australia (1/15), and India (1/15) (Table 1).
Table 1. General characteristics of the included studies.
Quality and risk of bias assessment (PEDro and MINORS).

3.4. Studies Included and Type of Intervention

Thirteen of the 15 selected studies were randomized controlled trials (RCTs). Nine of these reported follow-up data after the intervention [19,26,27,28,33,35,38,39]. The remaining two studies were a pilot study [36], an intervention study [34], and a pretest–posttest study [29], all with no comparison group. The interventions evaluated in these studies included aerobic exercise [32]; motor imagery [26,27,29]; prism adaptation [19,34,35]; pain exposure therapy [33,35]; sensorimotor training [36]; and mirror therapy [28,30,37,39]. Only one study [38] involved visual manipulation using virtual reality (Table 2).
Table 2. Outcome measures in pain, physical function and activities of daily living of the included studies.
To enhance interpretability, interventions were categorized into subgroups: (1) Mirror Therapy, (2) Graded Motor Imagery, (3) Prism Adaptation, (4) Pain Exposure Therapy, (5) Sensorimotor Training, and (6) Aerobic Exercise. This structure allows comparison of effects within and across modalities (Table 3, Table 4 and Table 5).
Table 3. Pain reduction in CRPS by intervention.
Table 4. Physical function.
Table 5. Activities of daily living.
Certainty analysis: The GRADE analysis showed that mirror therapy (MT) and pain exposure physical therapy (PEPT) reached a moderate level of certainty across pain, physical function, and activities of daily living outcomes. MT, supported by four RCTs, demonstrated consistent improvements in pain reduction, functional performance, and daily activity measures. PEPT, evaluated in three RCTs, also showed beneficial effects on range of motion and disability, with some variability in strength outcomes. In contrast, graded motor imagery (GMI), prism adaptation, virtual reality, aerobic exercise, and sensorimotor training were supported by single or small pilot studies, with methodological limitations and imprecision, leading to low or very low certainty ratings.

3.5. Effects of Physical Exercise on Pain, Physical Function, and Functional Outcomes

Only one included study specifically evaluated the effects of physical exercise in patients with CRPS [32]. This study implemented a four-week aerobic exercise program combined with conventional therapy, conducted five times per week in 30 min sessions. The intervention group showed significant post-treatment reductions in pain, hyperalgesia, and tenderness in the wrist and metacarpophalangeal joints, along with decreased movement-related pain throughout the day compared to the control group. Although no significant differences were observed in physical function as measured by the Brunnstrom stages of the upper limb and hand, the intervention group demonstrated significantly higher scores on the Functional Independence Measure (FIM), including both motor and cognitive domains (Table 2).

3.6. Effects of Neurocognitive Interventions Informed by CBT Principles on Pain

All 15 included studies assessed pain levels pre- and post-intervention using various validated scales. The most frequently used was the Visual Analogue Scale (VAS) (n = 10), followed by the Neuropathic Pain Scale (n = 4) and the Pain Inventory Index (n = 1). Overall, most studies reported significant reductions in pain following the intervention, with statistically significant differences compared to control groups in all but two studies [19,33].
One study observed a reduction in pain in patients with CRPS affecting both upper and lower limbs after pain exposure physical therapy; however, intention-to-treat analysis revealed no significant differences between groups [31]. In contrast, ref. [35] reported a statistically significant reduction in pain intensity immediately post-intervention and at 6-month follow-up in a cohort receiving pain exposure therapy compared to conventional care. Sensorimotor training also yielded positive results. One study [36] implemented a two-week protocol involving a Braille-like haptic task in various training modes and found that pain reduction correlated with the total training duration.
Three studies evaluated graded motor imagery in patients with upper limb CRPS. Refs. [26,27] found a significant reduction in pain compared to conventional therapy, with the most notable improvement occurring during the mirror movement phase. These effects persisted from 6 weeks to 6 months post-treatment. Similarly, ref. [29], despite lacking a control group, reported significant pain reductions, especially during the later phases of therapy involving mirror movements of the unaffected limb.
Mirror therapy interventions demonstrated consistent benefits. Ref. [37] found a significant pain reduction (p < 0.001) in CRPS type I patients, sustained up to one-month post-intervention. Refs. [28,30] also demonstrated that the combination of mirror therapy with conventional therapy produced significant pain improvement in patients with upper limb CRPS, with a treatment duration of four weeks. Both studies reported significant pain reductions and observed lasting pain reduction for up to six months. Ref. [39] showed that mirror therapy led to a significant pain reduction from 6.07 ± 1.58 to 3.93 ± 1.39 (p < 0.05) on the Numerical Pain Rating Scale (NPRS), with more pronounced effects than in the control group.
Regarding visual-perceptual interventions, ref. [19] found no significant pain reduction using prism adaptation therapy. In contrast, ref. [34] reported a 36% decrease in baseline pain following the same intervention. Ref. [38] demonstrated a significant pain reduction using virtual reality visual illusions (p = 0.037), while the control group showed no change (p > 0.05), suggesting that visual-based interventions may offer innovative pain management strategies for CRPS (Table 2).

3.7. Effects of Neurocognitive Interventions Informed by CBT Principles on Physical Function

Studies evaluated the impact of cognitive–behavioral interventions on physical function. Refs. [28,30] reported significant improvements in motor function in post-stroke CRPS patients following mirror therapy. Functional gains were measured using the Fugl–Meyer Assessment in the former and the Wolf Motor Function Test in the latter. Ref. [31] found a significant increase in active range of motion following pain exposure therapy compared to controls. Although muscle strength improved progressively in the intervention group, the between-group difference was not statistically significant. Ref. [29] reported improved grip strength in the affected limb during the acute phase of graded motor imagery therapy (Table 2).

3.8. Effects of Neurocognitive Interventions Informed by CBT Principles on Functional Outcomes or Disability Related to Daily Activities

Eight studies reported outcomes related to functional outcomes or disability associated with daily activities [28,29,30,31,33,34,35,39]. Mirror therapy appeared particularly beneficial. Refs. [30,39] found significant improvements in FIM motor scores following mirror therapy in patients with upper limb CRPS. Similarly, ref. [28] observed significant improvement in the Motor Activity Log (MAL) score. In all cases, mirror therapy contributed to enhanced functional independence.
Three studies examined pain exposure therapy in relation to disability associated with daily activities. Ref. [31] found no significant differences in EQ-5D index scores between groups, while another study by the same authors [33] reported a significant reduction in disability on the Pain Disability Index. Ref. [35] observed reductions in upper and lower extremity disability at six-month follow-up, measured via the Radboud Ability Questionnaire and the Ability to Walk Questionnaire, respectively. Results for other interventions were mixed. Ref. [29] reported no significant change in perceived upper limb function on the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. In contrast, ref. [34] reported a 10-point improvement on the Sickness Impact Profile (SIP) following prism adaptation therapy, suggesting potential for functional gains in daily living activities.

4. Discussion

This systematic review indicates that CBT-informed neurocognitive interventions—especially mirror therapy and graded motor imagery (GMI)—and, to a lesser extent, aerobic exercise, may reduce pain and improve physical function and daily activities in patients with CRPS when added to conventional care. Mirror therapy showed the most consistent benefits in upper-limb CRPS [28,30]. Evidence for aerobic exercise is preliminary and requires further study.
GMI may reduce pain when integrated with standard care; however, effects on physical function and daily activities remain uncertain, with only one study assessing these outcomes [28].
Findings for prism adaptation and pain exposure therapy were mixed. Some trials reported pain reductions, whereas others found no clear differences versus controls [19,31,33,34]. Two studies of pain exposure therapy reported improvements in disability [31,33], suggesting functional benefits. Prior literature aligns with these results. Smart et al. (2022) reviewed electrotherapy, cortically directed rehabilitation, electroacupuncture, and exposure-based therapies, noting that most studies were small and at high risk of bias; no intervention—including multimodal physical therapy—showed clear superiority for pain or disability [13].
Harden et al. (2022) likewise reported predominantly low-to-moderate methodological quality, largely due to small samples inherent to the rarity of CRPS, but highlighted positive effects of strengthening, body-awareness training, sensorimotor re-education, massage, and myofascial release [40]. In our review, mirror therapy emerged as the most consistently beneficial neurocognitive approach for upper-limb CRPS, whereas evidence for aerobic exercise—although compatible with previous reports—remains preliminary [41,42].
Evidence from Méndez et al. (2021) supports pain reductions following mirror therapy and motor imagery [43]. Schubert et al. (2021) found GMI particularly effective in acute CRPS, with associated improvements in cortical representation [44]. These findings support integrating CBT-informed neurocognitive rehabilitation into CRPS management.
CRPS requires multidisciplinary care due to its complex and persistent symptomatology. Reviews by Johnson et al. (2022) and Kraft et al. (2021) show that pain and motor dysfunction frequently persist long-term; 51–89% of patients continue to experience symptoms beyond 12 months, contributing to substantial disability [45,46].
The certainty of evidence (GRADE) ranged from very low to moderate, depending on intervention and outcome. Mirror therapy achieved moderate certainty for pain and functional improvement, limited by small samples and potential publication bias. Certainty for GMI was very low due to risk of bias, heterogeneity, and imprecision from small samples. Prism adaptation and virtual reality showed promising but low-certainty effects. Aerobic exercise and sensorimotor training were supported by very-low-certainty evidence. Overall, effects trend favorably toward neurocognitive interventions and exercise, but higher-quality studies are needed to strengthen confidence.

4.1. Strengths and Limitations

This review synthesizes evidence on physical exercise and CBT-informed neurocognitive interventions—mirror therapy and GMI—delivered by physical therapists for individuals with CRPS. These approaches, when added to conventional therapy, show potential for clinical implementation; however, more high-quality trials are required to confirm effectiveness.
Limitations include the small number of CRPS-specific studies, methodological heterogeneity in populations and protocols, and high risk of bias related to randomization, allocation concealment, and blinding. Outcome measures varied widely (e.g., VAS, NRS, DASH, WMFT, EQ-5D), preventing meaningful pooling. Intervention protocols differed in duration, frequency, content, and co-interventions, further limiting meta-analysis and risking misleading estimates. We therefore used a narrative synthesis with GRADE tables to appraise the evidence. These factors reduce confidence in current estimates and underscore the need for rigorous trials with standardized outcomes and clearer reporting.
Most studies did not report sufficient data (means, standard deviations, or adjusted estimates) to calculate standardized effect sizes with 95% confidence intervals. As a result, outcomes were often limited to p-values or mean changes, hampering cross-study comparisons. Future trials should consistently report standardized effect sizes and confidence intervals to improve comparability and clinical interpretation.
Formal subgroup or moderator analyses were not feasible due to few studies per category and inconsistent reporting of intervention duration, provider characteristics, and patient subgroups (e.g., post-stroke vs. post-fracture). Although mirror therapy appeared more consistent in upper-limb CRPS and GMI was mainly applied in post-stroke populations, the evidence is insufficient to draw firm conclusions. Standardized reporting is needed to enable stratified analyses and provide clearer clinical guidance.
Training is another gap. Few studies described how therapists were prepared to deliver GMI, mirror therapy, or pain exposure therapy. Future research should standardize training protocols and evaluate how therapist competence influences outcomes.
Finally, interdisciplinary collaboration is essential. Combining physiotherapy with explicit psychoeducation and mental-health support may enhance adherence and address the biopsychosocial complexity of CRPS.

4.2. Research Priorities

Future work should address methodological gaps through adequately powered, multicenter randomized controlled trials with long-term follow-up. Direct head-to-head comparisons among neurocognitive interventions (e.g., mirror therapy, GMI, prism adaptation, exposure therapy) and versus conventional physiotherapy are needed to determine relative efficacy. Factorial designs combining modalities (e.g., aerobic exercise plus mirror therapy) should explore potential synergy. Trials should incorporate mechanistic outcomes—quantitative sensory testing, neuroimaging, and psychological assessments (e.g., fear-avoidance, catastrophizing)—to link clinical change with underlying processes. Protocols should be standardized (at least ~12 weeks, two sessions per week) to improve comparability and inform guidelines.

4.3. Public Health Significance

CRPS imposes a substantial burden on patients and health systems. Non-pharmacological guidelines increasingly recognize the role of physical exercise as a modulatory intervention for this population. Future studies should adopt standardized outcomes: pain (Visual Analogue Scale), motor function (Fugl–Meyer Assessment or Wolf Motor Function Test), strength (dynamometry), and activities of daily living (DASH, Functional Independence Measure). Protocols should last ≥12 weeks with at least two sessions per week, and include well-defined control groups to support robust, generalizable recommendations.

5. Conclusions

Physical exercise and CBT-informed neurocognitive interventions show potential benefits for pain, physical function, and daily activities in CRPS. The evidence base remains limited, heterogeneous, and methodologically variable, highlighting the need for high-quality, multidisciplinary trials.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm14196820/s1, PRISMA 2020 Checklist. Ref. [23] is cited in the Supplementary Materials.

Author Contributions

L.T.O.-M.: Conceptualization; formal analysis; investigation; resources; validation; visualization; writing—review and editing. M.F.S.-O.: Conceptualization; formal analysis; investigation; resources; validation; visualization; writing—review and editing. M.A.M.-O.: Conceptualization; formal analysis; investigation; resources; validation; visualization; writing—review and editing. J.F.G.-G.: Investigation; resources; validation; visualization; writing—review and editing. G.P.R.-T.: Investigation; resources; validation; visualization; writing—review and editing. D.S.Q.-L.: Conceptualization; formal analysis; investigation; resources; validation; visualization; writing—review and editing. All authors have read and agreed to the published version of the manuscript.

Funding

This research has been funded by the General Directorate of Investigations of Universidad Santiago de Cali under call No. DGI 01-2025.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Data exchange not applicable—no new data generated.

Conflicts of Interest

Author G.P.R.-T. was employed by Clínica de Occidente; however, this does not imply any commercial or financial relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Appendix A

Table A1. Combination of search terms.

Appendix B

Table A2. Excluded studies.

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