Redefining pain and mental health management in cervical spondylosis: Electroacupuncture as a neuroinflammatory modulator and multimodal therapeutic innovation

Abstract

This editorial examines the constraints and novel approaches to management of cervical spondylosis patients with generalized anxiety disorder. Cervical spondylosis is a prevalent degenerative illness that often coexists with generalized anxiety disorder, which can cause pain and diminishing functional capacity. The loop of pain, anxiety, and inflammation diminishes the effectiveness of standard medications and rehabilitation, resulting from the interaction of neuroinflammation, central sensitization, and maladaptive pain processing. Electroacupuncture (EA), integrating traditional acupuncture with low-frequency electrical stimulation, has the capacity to modify pain and inflammatory pathways. EA stimulates the release of endogenous opioids, regulates cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha, and increases anti-inflammatory markers including IL-10 and transforming growth factor-β. It also augments motor and sensory functions, alleviates inflammation, and rehabilitates cognitive processes. Throughout an eight-week trial, a recent study showed that EA significantly reduced back pain, disability, and anxiety, while simultaneously decreasing inflammatory biomarkers, indicating strong connections between symptom relief and biochemical improvement. EA alleviates the pain-anxiety loop, enhancing its use as an adjunct therapy by targeting inflammation. EA is a multimodal strategy that improves quality of life, reduces reliance on pharmaceuticals, corresponds with mechanism-based therapy, and is clinically safe. Moreover, its advantageous safety profile yields socioeconomic benefits by lowering healthcare costs, enabling workforce reintegration, and improving access to adjunct medicines. This editorial advocates for the incorporation of EA into clinical practice to optimize treatment outcomes, enhance quality of life in certain patient populations, and improve symptom management.

Key Words: Cervical spondylosis; Generalized anxiety disorder; Electroacupuncture; Neuroinflammation; Pain-anxiety-inflammation cycle; Central sensitization; Endogenous opioids; Cytokines; Multimodal therapy; Socioeconomic impact

Core Tip: Cervical spondylosis is frequently comorbid with generalized anxiety disorder, creating a loop of pain-anxiety-inflammation that complicates therapy. This editorial proposes electroacupuncture (EA) as a possible treatment that can reduce pain, anxiety, and functional impairment in chronic stress patients with generalized anxiety disorder by influencing neural inflammation and the release of endogenous opioids. EA aids in regulating inflammatory signals and restoring brain function, complementing conventional therapy. Due to its superior safety profile and potential cost savings, EA offers a novel, evidence-based approach to enhance quality of life, decrease medication usage, and alleviate both physical and mental symptoms in these patients.

INTRODUCTION

The study by Li et al[1], evaluated electroacupuncture (EA) in a retrospective cohort of 83 patients with cervical spondylosis (CS)-related pain and comorbid generalized anxiety disorder (GAD). After 8 weeks of EA treatment, patients showed significant reductions in pain, anxiety symptoms, and key neuroinflammatory markers such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). Improvements in pain were strongly correlated with decreases in anxiety and inflammation. These findings suggest that EA may be an effective integrative therapy that simultaneously targets pain, anxiety, and neuroinflammatory processes in this population. CS is a common degenerative condition of the cervical spine, marked by substantial degeneration of intervertebral discs, facet joints, and surrounding ligamentous structures. The overall frequency rates vary from 30% to 50% within middle-aged and older demographics, contributing to a significant rise in healthcare burden. The principal symptoms and problems that markedly affect overall quality of life encompass cervical pain, rigidity, and radicular manifestations, with severe instances potentially resulting in myelopathic sequelae that partially impair functional capacity. This intricate disorder involves mechanical compression of cerebral structures, vascular inadequacy, and inflammatory processes that sustain tissue deterioration and nociceptive transmission. Neuroinflammation is acknowledged as a critical factor in the initiation of acute pain and its progression to neuropathic and chronic pain[2]. The conventional management of CS-related pain mostly entails a combination of pharmacological interventions, including non-steroidal anti-inflammatory drugs, muscle relaxants, and antidepressants, in conjunction with physical therapy, and, in resistant cases, surgical procedures. Opioid consumption causes changes in brain activity in chronic pain patients undergoing multidisciplinary treatment, with differing reactions between users and non-users[3]. Nevertheless, current treatments mainly yield inadequate results for people with coexisting anxiety disorders. The incidence of GAD among patients with chronic cervical pain ranges from 15% to 28%, significantly above that of the general population. This comorbidity creates a complex bidirectional relationship in which pain worsens anxiety symptoms, while anxiety heightens pain perception through brain sensitization and altered pain processing pathways. In addition to supraspinal effects, chronic pain causes maladaptive changes in spinal nociceptive processing. Dorsal horn neurons experience phenotypic modulation, leading to heightened production of pro-nociceptive agents such substance P and calcitonin gene related peptide. GABAergic interneurons collectively reduce their inhibitory function, resulting in heightened hyperexcitability of spinal networks. This spinal sensitization enhances supraspinal networks, hence amplifying the chronic pain-cognition feedback loop. Neuroinflammatory mechanisms intensify these anomalies[1]. Activated microglia and astrocytes release pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, thereby sensitizing neurons in both the spinal cord and brain. These cytokines impair synaptic homeostasis by suppressing brain-derived neurotrophic factor production and altering the glutamate/γ-aminobutyric acid balance, hence promoting central sensitization and cognitive deterioration. Researchers have identified a gene in the bloodstream whose modified activity correlates with inflammation and immune system functionality within the neurological system. This pertains to the degree of pain that an individual can endure and their sensitivity to it[4]. EA, an enhanced variant of traditional acupuncture that incorporates the application of little electrical currents between pairs of acupuncture needles, has emerged as a dependable treatment for diverse pain disorders. The neurobiological foundation of EA involves various processes, including the release of endogenous opioids, modification of autonomic nervous system function, and anti-inflammatory actions. Recent experimental and clinical investigations have demonstrated the ability of EA to inhibit pro-inflammatory cytokines, such as IL-6 and TNF-α, while enhancing anti-inflammatory mediators through vagal sympathetic pathways. Acupuncture stimulates IL-10 production by enhancing regularly T cell activation or polarizing M1 macrophages towards the M2 phenotype. The subsequent elevation in M2 macrophages also enhances transforming growth factor-β levels, leading to anti-inflammatory benefits. EA mitigates inflammatory areas and inhibits the release of substance P[5]. EA is included into traditional acupuncture, demonstrating significant advantages for cervical radiculopathy. Ongoing randomized controlled trials are comparing the efficacy of EA vs acupuncture[6]. Acupuncture shows a distinctive regulatory impact in individuals with chronic pain, influencing the somatosensory cortex and associated brain networks in a manner that differs slightly from placebo treatments[7]. EA analgesia mainly involves inhibiting sensory spinal cord signals, modulating the release of substances like TNF-α, and regulating axonal reflexes and nerve impulses, thereby diminishing pain perception. Nevertheless, EA enhances the microenvironment of the wounded nervous system by elevating levels of endogenous neurotrophic factors and diminishing inflammation, therefore reconstructing neuronal circuits and reinstating motor and sensory functions[8]. The study by Li et al[1] evaluated the efficacy of EA for CS-related pain in patients with concurrent GAD, monitoring anxiety symptoms and neuroinflammatory markers. They showed that after an 8-week period of EA treatment, there were significant reductions in pain intensity, functional impairment, anxiety symptoms, and neuroinflammatory markers, with evidence of linkages among these outcomes. The bidirectional association between pain and anxiety was obvious in correlation studies, supporting the concept of the ‘pain-anxiety-inflammation’ cycle; pain exacerbates anxiety, anxiety intensifies pain, and both are mediated by inflammation. By addressing neuroinflammation, EA may disrupt this cycle, accelerating progress across various symptom categories. These findings indicate the therapeutic potential of EA as an integrative method for alleviating pain and anxiety in patients with CS and concomitant GAD, possibly through the modulation of neuroinflammatory pathways. EA may mitigate neuroinflammation via the cholinergic anti-inflammatory pathway, wherein acetylcholine from the vagus nerve activates α7 nicotinic acetylcholine receptors (α7nAChR) on immune and glial cells, thereby inhibiting nuclear factor kappa-B signaling, decreasing pro-inflammatory cytokines (e.g., IL-6 and TNF-α), and promoting anti-inflammatory mediators such as IL-10. Low-intensity stimulation at ST36 can activate a vagal-adrenal anti-inflammatory axis, resulting in catecholamine release and systemic cytokine suppression, thus establishing a neuroanatomical connection between acupoint stimulation and immunological regulation pertinent to pain and anxiety. The convergent pathways correspond with the cytokine profile presented and provide a credible foundation for interrupting the pain-anxiety-inflammation cycle in chronic stress with GAD (refer to Figure 1).

Figure 1 Proposed electroacupuncture-driven neuroimmune mechanism in cervical spondylosis with comorbid generalized anxiety disorder. Low-intensity electroacupuncture at ST36 engages somatotopic, intensity-specific vagal circuits and α7 nicotinic acetylcholine receptors on immune/glial cells to inhibit nuclear factor kappa-B, decrease tumor necrosis factor-alpha/interleukin-6, and increase interleukin-10, while a parallel vagal-adrenal branch contributes to systemic cytokine suppression, jointly disrupting the pain-anxiety-inflammation cycle. α7nAChR: Α7 nicotinic acetylcholine receptors; EA: Electroacupuncture; NTS: Nucleus tractus solitarius; DMV: Dorsal motor nucleus of the vagus; NF-κB: Nuclear factor kappa-B; TNF: Tumor necrosis factor; IL: Interleukin; TGF: Transforming growth factor; CS: Cervical spondylosis; GAD: Generalized anxiety disorder.

CLINICAL IMPLICATIONS

Li et al’s work[1] demonstrates significant clinical implications for managing CS-related discomfort in patients with concurrent GAD. The shown efficacy of EA in simultaneously alleviating physical pain and psychological symptoms signifies a paradigm change towards integrated, multimodal treatment strategies that acknowledge the complex bidirectional link between chronic pain and anxiety disorders. The substantial reduction in pain intensity and functional dysfunction, symptomatic of alleviation and enhancement of patients’ daily functioning, is achievable through EA and its compromise in CS. The concurrent alleviation of anxiety symptoms, without altering pharmacological anxiolytic regimens, demonstrates EA’s efficacy as a beneficial treatment for the psychological distress commonly associated with chronic pain. Conventional treatment is inadequate for simultaneously addressing both anxiety and pain, often failing to manage them concurrently. Additionally, pharmacological interactions can impact and restrict prescription usage, complicating the pursuit of dual benefits. Comprehending the function of neuroinflammation in pain and anxiety establishes a scientific foundation for the effects of EA, suggesting that disrupting the persistent pain-anxiety-inflammation loop is achievable through targeting inflammation. The study indicates that clinicians should regard inflammation management as a crucial approach for treating patients with both musculoskeletal and mental problems. The identification of baseline anxiety severity, inflammatory marker levels, and symptom duration as predictors of treatment response can facilitate personalized care. Furthermore, early intervention in patients exhibiting moderate-to-severe anxiety and elevated inflammation may yield improved outcomes, thereby endorsing the timely and targeted application of treatment. Considering EA’s safety protocols, minimal side effects, absence of significant drug interactions, and its compatibility with multimodal treatment strategies, EA can function as an adjunct or secondary therapy alongside conventional medications and rehabilitation approaches. Healthcare professionals must explore integrating screening for anxiety and inflammation in patients with chronic stress to ensure comprehensive care that includes emotional assessment. The study recommends the incorporation of EA into clinical practice, which enhances symptom management, optimizes treatment efficacy, and significantly improves the quality of life for patients with CS and comorbid GAD. It also facilitates a transition towards integrated, mechanism-based treatments that address the interconnections among pain, mental health, and inflammation.

CLINICAL IMPORTANCE

Comorbid GAD with CS imposes significant socioeconomic difficulties due to its prevalence, resulting in long-term incapacity and health-related expenses. Indirect losses may occur for both individuals and society, often manifesting as decreased productivity, absenteeism, and worse quality of life. EA has demonstrated therapeutic efficacy and offers socioeconomic advantages by reducing reliance on costly medications and invasive procedures that predominantly carry risks and side effects. EA has reduced health care utilization associated with managing medication reactions or surgical complications due to its robust safety profile and few adverse effects. EA has significantly enhanced disability associated with chronic pain, demonstrating therapeutic advantages that last beyond the present therapy period, underscoring its clinical significance[9]. By alleviating both pain and anxiety symptoms, EA enhances functional capacity, facilitates an earlier return to work, and increases engagement in society. This may also aid in reducing chronicity, diminishing long-term disability, and reducing the larger socioeconomic load when administered early, particularly in patients with a shorter symptom duration. The extensive accessibility and integration of EA into collaborative care may reduce disparities, enhance treatment adherence, and improve patient satisfaction. Access to EA is constrained by issues like as insurance coverage, pricing, and the availability of practitioners. Integrating EA into normal care routes for CS and GAD may yield both socioeconomic advantages and therapeutic benefits.

CLINICAL FEASIBILITY ADDENDUM

For clinical translation, EA protocols must explicitly define acupoint selection, include at least one point with demonstrated autonomic anti-inflammatory data, such as ST36, along with stimulation intensity/frequency, session duration, and total course length to ensure reproducibility across various contexts. Delivery must be conducted by qualified and certified acupuncturists adhering to local safety regulations, accompanied by proper documentation and adverse event monitoring to guarantee consistent practice quality. Collaboration among multidisciplinary teams (pain medicine, rehabilitation, and mental health) with established objectives for pain, functionality, and anxiety can promote practical implementation in standard treatment. A concise, clear explanation of the autonomic and α7nAChR-mediated anti-inflammatory reasoning, along with a time-limited monitored trial, can alleviate patient scepticism and facilitate collaborative decision-making.

SOCIOECONOMIC FACTORS

This study primarily examines the clinical efficacy of EA for CS with GAD, while also emphasizing the broader socioeconomic issues that influence patient outcomes and healthcare delivery. The high frequency, enduring handicap, and associated healthcare costs have imposed a significant socioeconomic burden due to chronic pain syndromes, including CS. Indirect economic losses for individuals and society mostly stem from reduced productivity, increased absenteeism, and diminished quality of life resulting from chronic sickness. It demonstrates substantial cost savings while enhancing the quality of life for those suffering from pain and comorbid mental health conditions through the integration of acupuncture into traditional healthcare systems[10]. The inclusion of EA as a treatment diminishes reliance on expensive pharmaceuticals and invasive procedures that carry dangers, hence offering economical advantages. The reduced need to monitor drug reactions and surgical complications—areas in which EA demonstrates a strong safety profile and minimal side effects—may contribute to decreased healthcare utilization. EA can enhance functional capacity and overall well-being, facilitating an earlier return to work and social life by alleviating both pain and anxiety symptoms. Access to surgical interventions for cervical myelopathy is influenced by private insurance status, which correlates with an increased likelihood of receiving advanced procedural treatments, hence considerably impacting socioeconomic disparities[11]. Socioeconomic issues—such as insurance coverage, pricing, and geographic accessibility of qualified practitioners—might be influenced by access to multimodal therapies like EA. To diminish care inequities for people with chronic musculoskeletal and mental health disorders, we propose enhancing access to EA and augmenting insurance coverage. Early care in patients with shorter symptom duration may avoid chronic symptoms, reduce long-term disability, and diminish larger socioeconomic impacts, resulting in improved results. In sustainable healthcare, patient happiness and treatment adherence are crucial and can be enhanced by incorporating EA into multidisciplinary care. In summary, the adoption of EA into standard therapy for chronic pain and GAD can ensure clinical improvement and socioeconomic benefits by reducing healthcare expenditures, enhancing employment participation, and resolving healthcare disparities associated with these disorders.

CONCLUSION

This study identifies EA as an effective method for reducing chronic pain associated with CS and concurrent GAD by addressing the neuroinflammatory process. The results demonstrate substantial enhancement in physical function, psychological distress, and inflammatory markers, corroborating the multiple therapeutic effects of EA. This approach not only improves daily functioning but also reduces reliance on medicine and its attendant hazards. Clinically, EA represents a more promising multimodal intervention. Economical and accessible therapy that reduces productivity losses and enhances healthcare equity, resulting in a substantial impact, is achievable using EA. Early EA integration can considerably reduce chronicity and long-term handicap, alleviating the social load. Integrating EA into multidisciplinary care may improve patient adherence, satisfaction, and sustainable healthcare delivery[1]. However, the limitations include the necessity for extensive investigations and the examination of effects beyond the 8-week intervention period. Future research must identify patient benefits, optimize therapies, and evaluate cost-effectiveness across various healthcare settings. These results support the efficacy of EA interventions based on physiological responses, offering both therapeutic and socioeconomic advantages, thus representing a significant enhancement to routine care for individuals with CS and comorbid GAD.