Chronic pain in the neck and shoulders (CNSP) is a common musculoskeletal condition that greatly affects the well-being and work performance of those who suffer from it. It is characterized by persistent discomfort in the cervical and shoulder regions lasting for more than 3 months (Cohen, 2015). The incidence of CNSP is notably high, with a systematic review reporting global annual and lifetime prevalence rates of 37.2 and 48.5%, respectively (Fejer et al., 2006). A recent analysis of healthcare costs in the U.S. revealed that low back and neck pain contribute the highest medical expenditures among 154 diseases, with an estimated total of $134.5 billion (Dieleman et al., 2020; Murray et al., 2013).

While the pathology of CNSP involves local musculoskeletal dysfunction, growing evidence implicates maladaptive neuroplasticity within the central nervous system. Previous neuroimaging studies have established a link between CNSP and structural alterations in the cerebral cortex, distinguishing patients from healthy controls (HCs) (De Pauw et al., 2019; Niddam et al., 2019). For instance, cortical morphology appears to vary by etiology: reduced volume in the precentral and superior temporal gyri has been observed in chronic whiplash-associated neck pain, whereas cortical thickening in the superior parietal lobule has been reported in idiopathic neck pain (De Pauw et al., 2019). Similarly, surface-based analyses in chronic shoulder pain have revealed reduced sulcal depth in the sensorimotor and insular. Crucially, these structural anomalies are not merely epiphenomena but are clinically relevant; cortical thickness and sulcal depth in these regions have been shown to correlate significantly with motor deficits, pain intensity, and pain-related emotional dysregulation (Niddam et al., 2019). These findings suggest that CNSP is associated with a disruption in the brain’s structural integrity, potentially affecting networks involved in nociception and sensorimotor integration.

Although the cross-sectional association between brain structural abnormalities and chronic pain is well-documented, the longitudinal trajectory of these changes following clinical intervention involves complex dynamics that remain under-explored in CNSP. Prior longitudinal research in chronic low back pain (CLBP) provides compelling evidence that structural deficits are not permanent but can be reversible. Specifically, Seminowicz et al. (2011) demonstrated that effective pain relief following surgery or injections resulted in increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), primary motor cortex, and anterior insula—changes that correlated directly with reductions in pain and physical disability. Conversely, brain morphology can also exhibit rapid plasticity in response to specific pharmacological interventions. For instance, short-term opioid administration in CLBP patients was shown to induce volumetric changes in reward- and affect-processing circuitry, such as the amygdala and inferior frontal gyrus, with some alterations persisting even after drug cessation (Younger et al., 2011). These divergent findings suggest that post-treatment cortical changes are dynamic and may depend heavily on the specific therapeutic modality and clinical outcome. Currently, it is unclear whether the specific brain structural abnormalities in CNSP patients can be restored following minimally invasive intervention. Furthermore, clinical outcomes for CNSP treatments are often heterogeneous; while many patients experience relief, a subset remains refractory to treatment (Li et al., 2014). This variability highlights the urgent need for objective neural markers to stratify patients. Recent research supports the clinical utility of this approach; for instance, a study integrating neuroimaging data with clinical metrics successfully identified distinct migraine subgroups that exhibited significantly different response rates to electroacupuncture (18% vs. 44%), thereby providing a concrete intermediate marker for treatment selection (Liu et al., 2023). Identifying similar baseline neuroanatomical features in CNSP could accelerate the development of neurophysiological subtypes, moving beyond a “one-size-fits-all” model toward personalized pain management.

To address these knowledge gaps, this study employed an exploratory surface-based morphometry (SBM) (Argall et al., 2006) approach to investigate whole-brain cortical alterations. We recruited a cohort of CNSP patients undergoing minimally invasive interventional treatments and acquired high-resolution magnetic resonance data at baseline and at a 3-month follow-up. The specific aims of this study were twofold: (1) to determine whether baseline cortical structure patterns can serve as prognostic markers to predict clinical treatment outcomes; and (2) to examine the longitudinal plasticity of the cerebral cortex following pain relief. By characterizing these morphological changes without a priori regional assumptions, we aim to provide robust longitudinal evidence clarifying the central mechanisms of CNSP recovery.

This prospective observational study was conducted at the Affiliated Hospital of North Sichuan Medical College. The Ethics Committee of the Affiliated Hospital of North Sichuan Medical College granted approval for the procedures (Approval No. 2023ER95-1), and all procedures were carried out in full compliance with the principles outlined in the Declaration of Helsinki. Written informed consent was obtained from all participants. They were thoroughly informed about the study prior to their participation.

In the present study, we utilized surface-based morphometry (SBM) to investigate the longitudinal changes in cortical morphology (CT, GI, SD, and FD) in patients with CNSP before and 3 months after minimally invasive intervention. Our analysis yielded three main findings: (1) CNSP patients exhibited widespread cortical structural abnormalities at baseline, primarily involving regions associated with pain perception, emotional processing, and cognitive regulation; (2) minimal invasive intervention not only significantly alleviated pain but also reversed many of these cortical alterations, suggesting a trend towards structural normalization; and (3) specific baseline cortical features and their subsequent recovery were significantly correlated with clinical pain relief. Below, we interpret these widespread morphological changes by categorizing the affected regions according to their functional roles in the multidimensional experience of pain.

In this study, CNSP patients exhibited widespread cortical morphological alterations. To better understand the pathophysiological implications of these structural changes, we discussed the findings in the context of the functional roles of the affected regions. First, concerning the sensory-discriminative dimension of pain, we observed significant cortical thinning (reduced CT) and sulcal deepening (increased SD) in the bilateral central sulcus, paracentral lobule, and posterior cingulate cortex. These regions are fundamental components of the sensorimotor network, responsible for encoding the location and intensity of nociceptive stimuli (Jensen et al., 2023). We postulate that the structural alterations observed in these primary sensorimotor areas might be linked to activity-dependent plasticity driven by peripheral nociceptive input (Apkarian et al., 2004). Continuous nociceptive bombardment from the cervical spine leads to excessive neural activity in these projection areas. It is plausible that this chronic hyperactivity could potentially induce excitotoxicity or synaptic pruning, ultimately manifesting as neuronal loss and macroscopic gray matter atrophy (May, 2008). These results are partially consistent with previous findings of motor cortex atrophy in patients with chronic neck pain (Coppieters et al., 2018), supporting the hypothesis that the structural integrity of the sensorimotor cortex may be compromised by the persistent physiological demands of processing pain signals. Second, regarding pain emotional processing, we also observed a pattern of structural atrophy (reduced CT and/or increased SD) in key limbic and prefrontal regions, specifically the left anterior cingulate cortex (ACC), bilateral prefrontal cortex, and bilateral insula. The insula and ACC are core components of the “pain matrix,” crucial for integrating the affective-motivational dimension of pain (e.g., suffering) and interoceptive awareness (Bubb et al., 2018). The cortical thinning in these regions might reflect a deleterious consequence of chronic emotional stress. We speculate that the sustained engagement of these emotional hubs in processing negative affect could lead to neurodegenerative changes similar to those seen in the sensorimotor cortex. This interpretation aligns with previous studies showing gray matter loss in the ACC and insula in various chronic pain conditions (Apkarian et al., 2004), which is often associated with deficits in emotional regulation and increased pain unpleasantness (Valet et al., 2009). However, a distinct morphological pattern was observed in other regions associated with emotional and cognitive integration. Specifically, CNSP patients exhibited an increased Gyrification Index (GI) in the left lateral orbital frontal cortex (OFC), anterior cingulate cortex, posterior cingulate cortex, lingual gyrus, superior frontal gyrus, and the right medial orbital frontal cortex, lingual gyrus, and paracingulate cortex. Unlike the atrophy described above, higher gyrification typically reflects a more complex cortical folding pattern (Luders et al., 2006). We hypothesize that this increased complexity in these specific limbic and associative regions might represent a form of structural reorganization or adaptive plasticity (Fernández et al., 2016). Rather than definitive compensation, we cautiously interpret this phenomenon as a potential response to the complex demands of chronic pain. It is possible that the brain attempts to reorganize its local connectivity in these high-order processing areas to cope with the persistent emotional and cognitive load, resulting in increased cortical folding (Striedter et al., 2015; Klyachko and Stevens, 2003), although the precise cellular mechanisms require further investigation. Finally, structural alterations were evident in regions critical for pain cognitive regulation, specifically the left dorsolateral prefrontal cortex (DLPFC) and bilateral precentral gyrus, which showed significant cortical thinning. The DLPFC is a key node in the central executive network and plays a pivotal role in the “top-down” inhibition of ascending pain pathways (Lorenz et al., 2003). Structural deficits in the DLPFC are widely reported in chronic pain pathology (Apkarian et al., 2004). The cortical thinning observed in our study may potentially reflect a maladaptive response to the sustained demand for cognitive pain control. While the mechanism remains to be elucidated, this finding is consistent with meta-analyses demonstrating DLPFC gray matter reduction across various chronic pain conditions (Smallwood et al., 2013), reinforcing the link between executive control networks and the maintenance of chronic pain states.

Regarding the longitudinal changes, our results demonstrated that 3 months after minimally invasive intervention, the significant alleviation of pain was accompanied by a widespread normalization of cortical morphology (CT, SD, and GI) across the previously identified abnormal regions. This observation of structural reversibility is clinically significant, as it suggests that the baseline cortical alterations likely represented a state of maladaptive neuroplasticity driven by chronic nociceptive input, rather than permanent neurodegeneration (Calderone et al., 2024; Marzola et al., 2023). We suggest that this restoration may be attributed to the brain’s intrinsic capacity for reorganization. Following the intervention, the reduction in nociceptive signals likely alleviated the “sensory load” on pain-related networks was reduced, allowing neural circuits to re-establish their structural homeostasis (Tataranu and Rizea, 2025). Similar patterns of treatment-induced structural changes have been documented in other chronic conditions, such as anxiety (Steiger et al., 2017), major depression (Xu et al., 2019), and chronic pancreatitis (Muthulingam et al., 2018), highlighting the potential of effective pain management to reverse maladaptive cortical remodeling.

While the longitudinal results highlight the potential for structural recovery, it is equally important to understand how individual differences in baseline cortical structure influence clinical outcomes. Specifically, we found that higher baseline CT in the precentral gyrus and paracentral lobule, as well as lower baseline SD (shallower sulci) in the cingulate cortex and central sulcus, were significantly correlated with greater pain relief (more negative VAS percent change) after treatment. These findings suggest a clear link between pre-treatment structural integrity and clinical outcomes. As discussed above, these sensorimotor and limbic regions are vulnerable to atrophy driven by chronic nociceptive input. Patients with relatively preserved cortical thickness and sulcal depth in these critical nodes may possess a higher “neural reserve” (Stern, 2009). This structural integrity likely reflects a more resilient neural network capable of effective sensory-motor integration and emotional modulation. Consequently, patients with “less damaged” cortical substrates may be more responsive to minimally invasive interventions, leading to more pronounced pain relief (Virtanen et al., 2014). Furthermore, a significant correlation was observed between higher baseline GI in the right medial orbitofrontal cortex (mOFC) and better treatment outcomes. Consistent with our hypothesis that increased gyrification represents an adaptive structural reorganization, a higher GI in the mOFC implies a more robust compensatory mechanism for emotional regulation. Since the mOFC is pivotal for context-dependent pain modulation and coping strategies (Roy et al., 2012), patients who have successfully developed this structural complexity may possess enhanced cognitive-emotional resources to process pain (Kringelbach, 2005). Therefore, a higher degree of adaptive gyrification at baseline may prime the brain to benefit more effectively from the reduction of peripheral nociceptive drive achieved by the treatment.

Finally, beyond baseline predictors, we further examined the dynamic relationship between symptomatic improvement and structural plasticity. We found that the magnitude of pain relief (VAS percent change) was significantly correlated with the extent of structural reversal—specifically, changes in cortical thickness in the left precentral gyrus and changes in SD in the left dorsolateral prefrontal cortex (DLPFC) and cingulate cortex. This synchronization might be attributed to use-dependent neuroplasticity (Bliss et al., 2016). As the therapeutic intervention effectively alleviates the chronic nociceptive burden, the maladaptive processing load in these sensorimotor and cognitive control hubs is reduced, thereby promoting structural normalization. Consequently, patients experiencing greater pain relief exhibited more pronounced structural restoration. This parallel trajectory between clinical efficacy and cortical remodeling mirrors findings in other successful therapeutic interventions, suggesting that the observed morphological recovery is indeed functionally relevant (Sartorius et al., 2016; Zhou et al., 2022).

In this study, although the minimally invasive interventions for CNSP patients were performed by a single surgeon using the same treatment method, and the analysis controlled for patients’ age, gender, and disease duration, the treatment efficacy may still be influenced by other uncontrollable factors [such as the degree of cervical disc herniation, spinal nerve root inflammation, postoperative care, etc. (Moustafa et al., 2024)]. Most importantly, the current study design lacked a control group receiving conservative therapy or sham intervention. Therefore, we cannot definitively attribute the observed cortical changes solely to the specific effects of the minimally invasive procedure, nor can we fully rule out placebo effects or the natural history of the disease. The interpretation of these changes as “recovery” or “adaptation” should be considered with caution. Furthermore, while we observed structural alterations in brain regions implicated in emotional processing (e.g., the anterior cingulate cortex and insula), the current study did not include specific behavioral assessments of anxiety or depression (such as the Self-Rating Anxiety Scale or Self-Rating Depression Scale). Chronic pain is frequently comorbid with emotional distress, which plays a crucial role in the “pain matrix (Bushnell et al., 2013).” The lack of these psychometric data prevents us from directly analyzing the correlation between the observed cortical changes in limbic regions and the patients’ emotional states. Future studies should include comprehensive psychological evaluations to better disentangle the specific contributions of sensory pain versus pain-related affect to cortical remodeling. Finally, it should be noted that the regions of interest (ROIs) used for the correlation analyses were defined based on the significant group differences observed at baseline. This analytical strategy introduces a circularity bias, often referred to as “double dipping,” which may potentially inflate the statistical strength of the observed correlations (Kriegeskorte et al., 2009). Ideally, this should be addressed using independent validation datasets or split-half cross-validation (Varoquaux et al., 2017). However, due to the limited sample size in the current study, such validation methods were not feasible without compromising statistical power. Therefore, the correlation results presented here should be interpreted as exploratory, and these findings require replication in future studies using larger, independent cohorts to confirm the robustness of the brain-behavior associations.

This study employed the surface-based morphometry method to analyze the MRI and clinical data of CNSP patients at baseline and 3 months after minimally invasive intervention, finding that CNSP patients exhibited abnormal cortical morphological changes in multiple brain regions associated with pain perception, emotional processing, and cognitive regulation, with some restoration observed after treatment. Furthermore, it was found that at baseline, the CT of the left precentral gyrus and left paracentral lobule, the SD of the left cingulate cortex and left central sulcus, and the GI of the right medial orbital frontal lobe were significantly correlated with the percent change of VAS scores. Changes in CT of the left precentral gyrus and changes in SD of the left cingulate cortex and left dorsolateral prefrontal cortex before and after the minimally invasive intervention were significantly correlated with the percent change of VAS scores. These findings provide valuable longitudinal data for understanding the central mechanisms of pain in CNSP patients and lay the foundation for individualized treatment based on cortical morphological changes in CNSP patients.