Revisiting chronic musculoskeletal pain as a biopsychosocial disorder

Abstract

Chronic musculoskeletal pain (CMP) is one of the world's health problems affecting millions of people. As musculoskeletal pain is chronic, it changes from nociceptive pain to mixed pain mediated by peripheral and central sensitization. CMP is a biopsychosocial disorder in which psychological factors, including anxiety and depression, significantly affect the pain experience and disability. In addition to these factors, pain coping strategies and social determinants of health also play important roles in the experience of chronic pain. In the recent issue of World Journal of Clinical Cases, conducted by Hamed et al, investigated psychiatric disorders, coping strategies, and quality of life in patients with CMP to better understand the clinical and psychosocial aspects of CMP. This editorial letter aims to critically appraise the multidimensional nature of CMP in light of the findings by Hamed et al, with a particular focus on clinical heterogeneity, psychiatric comorbidities, psychosocial stressors, and key determinants of impaired quality of life.

Key Words: Chronic musculoskeletal pain; Fibromyalgia; Psychogenic pain; Depression; Anxiety; Quality of life

Core Tip: A complicated biopsychosocial illness, chronic musculoskeletal pain is influenced by social determinants of health, coping mechanisms, psychiatric comorbidities, and central sensitization. In order to improve quality of life, evidence from Hamed et al emphasizes the necessity of integrated, interdisciplinary approaches that treat both psychological and physical aspects.

This editorial refers to “Chronic musculoskeletal pain disorder and its associated mental health conditions, comorbidities and psychosocial risk predictors” by Hamed et al, 2026; https://dx.doi.org/10.12998/wjcc.v14.i15.120217.

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INTRODUCTION

Chronic musculoskeletal pain (CMP) is defined in the International Classification of Diseases as ‘pain originating from bones, joints, muscles, or soft tissues that persists for more than three months[1]. CMP has a substantial impact on individuals and populations worldwide. It is currently the greatest cause of disability worldwide. Little is known about pain mechanisms in the musculoskeletal system, and current treatments have a limited effect for many individuals experiencing pain[2]. Management strategies are largely incomplete, and our understanding of the pain experience is limited. CMP is frequently combined with other psychophysiological conditions, often impacting several domains of an individual’s life. These issues have important public health implications. The challenge of managing CMP and the individual pain experience needs to be addressed to inform service development and improve outcomes for individuals living with pain. 22% of the global population live with some form of disability. Following the development of CMP, disease management often becomes difficult, and symptoms can persist for many years. Studies show that approximately 79%-92% of children with CMP have pain complaints that persist until the age of 12, and the disease shows significant persistence[3-5]. With CMP being the most common reason for sickness absence from work (after common minor illnesses) and only 59% of the working age population in the United Kingdom being in work, there is a pressing need to explore ways to prevent, reduce disability, and alleviate pain in this age group[6,7]. While we highlight the community and population impact of CMP, the individual experience of CMP is also important to acknowledge, with many people having moderate to severe disability, poorer quality of life, and increased risk of chronic disease (including cardiovascular disease, diabetes, and cancer)[8-10]. The United Kingdom National Health Service spends £5 billion every year on treating musculoskeletal pain; however, the prevalence of CMP is increasing. This, therefore, represents a huge burden on individuals and society and requires a more advanced and integrated healthcare approach[11]. The findings presented by Hamed et al[12] support the need to re-evaluate CMP within the framework of a biopsychosocial model. The intensity and persistence of pain are shaped not only by peripheral nociceptive stimuli but also by the dynamic interactions between psychological burden, sleep disturbances, cognitive processes, and the social environment. The prominence of maladaptive coping strategies and chronic stress as factors contributing to the persistence of pain indicates that focusing solely on symptom control is insufficient. Therefore, psychological assessment, sleep management, stress-reducing approaches, and, when necessary, psychiatric support, along with physical therapy and pharmacological treatments, should be considered integral components of a multidisciplinary treatment plan. The management of chronic pain can result in a reduction of pain, improvement in function and an overall enhancement of quality of life with the potential for optimal long-term outcomes.

These editorial letter addresses the findings of the study on CMP by Hamed et al[12]. The findings of the study are explained in the light of the current data on the subject matter. First, information regarding the prevalence and dimensions of CMP are provided. Next, the study’s findings are explained in the light of the biopsychosocial model of pain, its psychiatric comorbidities and their psychosocial determinants. Finally, the need to search for the potential role of immunological mechanisms in CMP is discussed. Such search is not yet sufficiently addressed in the literature[13,14].

UP-TO-DATE INSIGHTS INTO THE ROLE OF BIOPSYCHOSOCIAL FACTORS IN PAIN

Biological contributors to pain encompass physical stress, infection, underlying pathological processes, and tissue damage, which collectively might disrupt physiological homeostasis[15,16].

The results outlined in Table 1 show that CMP cannot be understood through nociceptive mechanisms alone — it is a multidimensional condition influenced by gender, psychiatric comorbidities, and psychosocial factors. This multifaceted structure will be discussed in more detail in the following sections. Although Hamed et al[12] did not directly evaluate immunological markers or infection-related parameters in their study, the biological basis of pain should not be overlooked. Indeed, increasing evidence in recent years shows that immune responses, particularly those mediated by pro-inflammatory cytokines, play a significant role in the development and persistence of CMP. Furthermore, these immunological mechanisms are thought to be closely intertwined with psychosocial stress, psychiatric comorbidities, and increased pain sensitivity. Therefore, the psychosocial findings presented by Hamed et al[12], when considered together with the underlying immunological processes of chronic pain, offer a more comprehensive biopsychosocial framework[17].

Table 1 Overview of major findings and their interpretive significance in chronic musculoskeletal pain.

Key finding	Findings in Hamed et al's study[12]	Interpretative implication	Interpretation boundary
Female predominance	Female patients accounted for 81.25% of the cohort	Suggests potential biological, psychosocial, and gender-related influences on susceptibility to chronic musculoskeletal pain	Female predominance alone does not establish hormonal or sex-specific biological mechanisms
High psychiatric comorbidity	Depression (37.5%) and anxiety (43.75%) were highly prevalent	Reinforces the biopsychosocial model by highlighting the close association between psychological distress and chronic musculoskeletal pain	The cross-sectional design does not determine whether psychiatric symptoms are causes, consequences, or mutually reinforcing factors
Prominent sleep disturbance	Clinically significant insomnia was reported in 87.5% of patients	Supports the concept of reciprocal interactions between sleep disturbance and chronic musculoskeletal pain	The temporal relationship between insomnia and pain cannot be determined from the available data
High burden of life stressors	Financial and occupational stressors (75%) and marital problems (60%) were common	Suggests that psychosocial stress may contribute to pain vulnerability and persistence	Associations do not demonstrate that psychosocial stress directly initiates or chronifies pain
Maladaptive coping strategies	Self-blame, denial, and behavioral disengagement were frequently reported	Highlights the potential contribution of cognitive and behavioral factors to pain perception and disability	Coping strategies were self-reported and should not be interpreted as causal determinants of persistent pain
Impaired quality of life	WHOQOL scores were substantially reduced in the physical, psychological, and social domains	Demonstrates the broad multidimensional burden of chronic musculoskeletal pain on daily functioning and well-being	Reduced quality of life reflects disease burden but does not identify the underlying biological mechanisms
Central sensitization	The combination of psychological distress, insomnia, maladaptive coping, and widespread symptom burden is compatible with a centrally amplified pain phenotype	Suggests that some patients may exhibit clinical features consistent with central sensitization	The study did not include quantitative sensory testing, neuroimaging, pain-threshold assessment, or mechanistic biomarkers; therefore, central sensitization cannot be confirmed
Lack of immunological assessment	No inflammatory biomarkers, cytokines, or infectious parameters were evaluated	Identifies an important knowledge gap and supports future multidisciplinary studies integrating biological and psychosocial assessments	Immune activation, neuroinflammation, and infection-related mechanisms cannot be inferred from the available data

WHOQOL: World Health Organisation Quality of Life.

Infection is a common biological stimulus for pain. In order to defend against infectious pathogens, the body mounts an inflammatory/immune response, which can itself produce pain[18]. The pro-inflammatory cytokines (e.g., interleukin-1beta, tumor necrosis factor, interleukin-6) and other bioactive substances (e.g., prostaglandins, bradykinin) produced during infection can sensitize primary afferent nociceptors such that they become hyperresponsive to exogenous stimuli and develop an increased sensitivity to endogenous substances produced by the body[19]. The immune response to infection is typically protective and resolves once the pathogen has been cleared[20]. However, persistent or unresolved infection can lead to chronic inflammation, either locally or systemically. This form of chronic inflammation can produce both peripheral sensitisation (whereby the peripheral terminals of nociceptive neurons become sensitised) and central sensitisation (whereby the excitability of nociceptive neurons within the spinal cord is increased)[21]. Many infectious diseases can also directly cause neuroinflammation (i.e., activation of immune cells and glial cells within the nervous system), further enhancing pain transmission and facilitating the development and maintenance of chronic pain[22-24]. The interactions between the immune system and the nervous system that occur in infection-induced pain are complex and determine whether the pain is acute or chronic[25]. However, this traditional peripheral model does not completely address chronic pain syndromes, where structural abnormalities are often absent despite significant symptom burden.

Hamed et al’s findings are consistent with, rather than definitive proof of[12], a centrally mediated model of CMP, as the study did not include direct mechanistic or biomarker-based evidence for central sensitization. The absence of demonstrable tissue damage, alongside the severity of reported pain, is compatible with a role for central sensitization in the pathophysiology of CMP, though this interpretation remains inferential. Moreover, the significant correlation observed between pain and psychiatric comorbidities suggests, rather than establishes, that chronic pain may reflect an interaction between emotional regulation systems and pain processing systems[12]. Unlike chronic widespread pain and fibromyalgia, for which numerous social and psychological risk factors and predictors have been studied in detail, more is unknown about the role of these factors in purely nociceptive chronic pain. However, recent evidence suggests that social and psychological factors are relevant for all forms of CMP and predict outcomes in all of them.

Pain that persists over time can be influenced by several factors, including life stress and socioeconomic status. For example, exposure to childhood trauma, low levels of formal education, social isolation, depression, and anxiety have all been associated with chronic pain and increased burden of somatic symptoms. A recent large population-based cohort study found the best predictors of new onset chronic widespread pain were related to the psychosocial screen and included the presence of somatic symptoms, illness behavior, and sleep problems. The perception of physical and emotional trauma is more predictive of health-seeking behavior than pain severity[26-30].

As shown in Table 1, the high burden of financial, occupational, and marital stressors reported by Hamed et al[12] lends support to the broader literature indicating that CMP duration, frequency, and intensity are shaped by cumulative life stress. These findings reinforce the concept that socioeconomic factors and stress are not separate from pain chronicification but are integral to it. While there may be several reasons why CMP might manifest differently in men and women, likely, sex-related differences in reports of pain and related behaviors cannot be attributed solely to psychosocial factors[31]. Reports of pain and behaviors related to pain may differ due to differences in activity levels, as well as cultural and social determinants that influence perceptions of pain. While some differences in pain reporting or expression may be due to symptom exaggeration, several indicators suggest that sex differences in CMP are real. For example, women with less than a high school education and women living in rural or non-metropolitan locations may be particularly vulnerable to chronic pain[32]. Sex differences in pain processing are additionally influenced by sex hormones, primarily estrogen, which can modulate pain experience at multiple levels, including pain processing structures and pathways in the central nervous system, neurotransmitter systems, and the hypothalamic-pituitary-adrenal axis. For example, studies have found that estrogen upregulates pain-inhibitory opioid receptors in the spinal cord and decreases activity in the anterior cingulate cortex, a brain region implicated in the experience of pain, in women with knee pain[33].

CMP should be viewed as a multifaceted condition shaped by the interplay of psychological, social, economic, and biological factors. Grasping its true nature calls for a multi-angle perspective rather than a single-lens approach. Going forward, research and treatment planning would benefit from a more integrative, cross-disciplinary approach — one that captures the full complexity of chronic pain and affects every day functioning. Such an approach could lead to more effective interventions and meaningfully improve quality of life for those living with the condition.

CONCLUSION

As also reflected in the study by Hamed et al[12], CMP pain is a biopsychosocial condition that cannot be explained solely by the degree of nociceptive input from the affected tissues. Biological, psychological, and other social factors influence patients’ perception of pain. The findings of this study are consistent with those of previous studies and underscore the substantial impact of psychiatric comorbidities and psychosocial stressors on the severity of reported symptoms and patients’ quality of life. However, the cross-sectional design, recruitment from specialized outpatient clinics at a single institution, marked female predominance, and reliance on patient-reported measures limit causal and mechanistic inference and may restrict generalizability. Furthermore, because of the relatively small sample size and single-center patient selection, only limited causal conclusions can be drawn, and the findings may not be generalizable to other groups of patients with CMP.