Chronic musculoskeletal pain disorder and its associated mental health conditions, comorbidities and psychosocial risk predictors

Abstract

BACKGROUND

Chronic musculoskeletal pain (CMP) is a functional neurological symptom that manifests as real pain originating from the brain due to mental health issues and a combination of factors.

AIM

To determine the patterns of CMP, the associated emotional, behavioral and social components and predictors of pain’s impact on daily life.

METHODS

This cross-sectional study included 160 patients with CMP (males = 30; females = 130). Data collection included demographics and clinical features of pain. Pain severity was measured using the Visual Analog Scale questionnaire. Psychiatric evaluation included psychiatric interviewing and psychometric questionnaires. They included Depression Anxiety Stress Scale, Insomnia Severity Index, Fatigue Severity Scale, Life Stressors, Brief Cope Inventory, and World Health Organization quality of life (WHOQOL).

RESULTS

Patients had mean age of 46.63 ± 6.23 years and mean duration of pain of 16.28 ± 3.05 months. Localized pain was more common (78%, n = 125) than diffuse (fibromyalgia) (22%, n = 35), with low back pain being the most frequent localized pain (30.4%). Approximately 37.5% (n = 60) had major depression and 43.75% (n = 70) had anxiety disorder. Patients had high scores and frequencies of depression, anxiety, and stress symptoms, insomnia fatigue and poor WHOQOL scores. Life stressors were reported in 60%-75%. Maladaptive copying strategies to pain were reported in 45%-60%. Multiple regression analysis showed that factors associated with low scores of physical domain of WHOQOL included duration of pain (β = 1.426; 95%CI: 0.565-3.428; P < 0.01), symptoms of depression (β = 2.356; 95%CI: 1.564-4.842; P < 0.01), anxiety (β = 1.232; 95%CI: 0.863-4.680; P < 0.01) and stress (β = 2.346; 95%CI: 1.620–6.550; P < 0.001), insomnia (β = 1.843; 95%CI: 1.648-3.642; P < 0.01) and low scores of psychological (β = 6.7; 95%CI: 2.30-8.640, P < 0.001) and social domains (β = 3.5; 95%CI: 5-12, P < 0.001) of WHOQOL.

CONCLUSION

CMP is more frequent in middle aged females than males. It is associated with emotional and behavioral abnormalities and resulted in impaired quality of life. It is due to central processing alterations influenced by psychosocial issues. Understanding the factors associated with CMP and prolonged disability, including mental health, is crucial for developing effective treatment strategies.

Key Words: Chronic musculoskeletal pain; Fibromyalgia; Psychogenic pain; Depression; Anxiety; World Health Organization quality of life

Core Tip: Chronic musculoskeletal pain (CMP) is a common condition affecting 20%-30% of adults worldwide, with a higher prevalence in females. It manifests as persistent pain in muscles, bones, joints, tendons, or ligaments lasting over three months. CMP is a complex issue with medical, psychological, and psychosocial risk factors. It is also known as psychogenic musculoskeletal pain. Diagnosis of CMP requires a comprehensive evaluation by specialists and diagnostic tests. Treatment options include medications, physiotherapy, and psychotherapy. Researchers suggest that psychogenic pain involves intricate neurobiological and biopsychosocial elements. Cultural considerations in pain reporting and expression are essential in managing patients with CMP.

INTRODUCTION

Chronic musculoskeletal pain (CMP) is a prevalent condition affecting around 20%-30% of the adult working population globally, with a higher incidence in women than men[1,2]. The prevalence of CMP is consistent across different ethnic groups, cultures, and countries[3]. CMP is characterized by persistent pain in muscles, bones, joints, tendons, or ligaments lasting more than three months, with a history of intermittent chronic pain episodes[4]. CMP can manifest as diffuse or localized pain, with diffuse CMP often referred to as fibromyalgia. The sensations associated with CMP include burning, aching, stabbing, or tingling, often accompanied by signs of pain hypersensitivity like hyperalgesia (excessive response to a painful stimulus) and allodynia (sensation of abnormal pain from a stimulus that shouldn’t cause pain)[5]. CMP is frequently linked to other somatic and mental health disorders including depression (approximately 30%-60%)[6], anxiety (approximately 40%)[6], post-traumatic stress (1.6%-29.2%)[7] and substance abuse disorders (approximately 40%)[8] which exacerbate its impact on individuals’ well-being.

CMP is a complex condition that is not solely explained by tissue damage, nociception, or neuropathic mechanisms, and may not correlate with identifiable physical findings[4]. It is considered a functional neurological symptom originating in the brain due to mental health issues[9]. Various terms are used to describe this type of pain, such as psychogenic musculoskeletal pain, functional musculoskeletal pain, amplified musculoskeletal pain syndrome, nociplastic pain and others. In Diagnostic and Statistical Manual of Mental Disorders, 5^th edition (DSM-5), CMP is classified as Somatic Symptom Disorder (SSD) with predominant pain[10]. In International Classification of Diseases 11^th Revision, it is classified as primary CMP and defined as presence of one or more areas of pain that accompany significant emotional distress (as anxiety, anger/frustration or depressive state) or functional disability (as interference in activities of daily living with reduced social interaction)[11]. Diagnosing psychogenic pain requires a comprehensive clinical evaluation involving various specialties such as Rheumatology, Orthopedics, Neurology, Psychiatry, and others, along with diagnostic tests and imaging scans to rule out other potential diagnoses. Treatment for CMP typically involves a combination of pharmacological[12] and non-pharmacological interventions like physiotherapy, acupuncture, and psychotherapy[13]. CMP can significantly impact physical and mental health, affecting daily activities and social interactions[14,15]. CMP poses a substantial burden on individuals, healthcare systems, and economies[16].

The pathophysiology of chronic pain involves central sensitization[17], alterations in brain regions related to attention, cognition, and emotions (cingulate cortex, insula and hippocampus)[17-21], impairments in endogenous pain inhibitory mechanisms[21], dysregulation of neurotransmitters and pathways like adrenergic and serotonin pathways[22] and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis[23]. The dorsal anterior and anterior middle cingulate cortices are implicated in integrating negative affect and cognitive control of pain[17]. The hippocampus is linked to negative expectancy and the memory of past pain, which can prime the nervous system for future episodes[18]. Research indicates that chronic stress or psychological trauma can lead to “central sensitization”, where the anterior cingulate cortex (ACC) becomes hyperexcitable and hypersensitive to even low-level peripheral signals[17]. Functional magnetic resonance imaging (MRI) studies have demonstrated significant hyperactivity in the dorsal ACC and the anterior insula in patients with fibromyalgia or psychogenic pain[17]. Advanced proton magnetic resonance spectroscopy has revealed elevated levels of glutamate, the brain’s primary excitatory neurotransmitter, and diminished levels of GABA, the brain’s primary inhibitory neurotransmitter, in the posterior insula and ACC of patients with central pain amplification creating an imbalance that favors excitation and pain signaling[20]. Studies reported lower enzymatic activity of catechol-O-methyltransferase, an enzyme that regulates the breakdown of dopamine, epinephrine, and norepinephrine, leading to higher levels of catecholamines and increased sensitivity to both psychological stress and physical pain[21]. Studies also indicated that dysregulation in the 5-HT transporter gene (SLC6A4) has been linked to fibromyalgia and other widespread pain syndromes[22]. When these pathways fail, minor sensations can be amplified into significant distress. Furthermore, studies have shown that chronic psychological distress or early-life trauma can “recalibrate” the HPA axis, leading to hypocortisolism or a blunted cortisol response which is reverse to the normal response in which acute stress excites the release of cortisol, suppresses peripheral nociceptors and relieves muscle pain[23].

It has been indicated that cultural factors influence pain reporting and attitudes toward pain expression[24]. Understanding the factors associated with musculoskeletal complaints and addressing mental health status are essential for developing effective treatment strategies.

This study aimed to provide a comprehensive understanding of psychogenic CMP and its associated factors. Its objectives were to investigate: (1) The CMP patterns; (2) The emotional, behavioral, and social aspects of pain along with comorbid physical and mental health conditions; (3) The related life stressors and coping strategies; (4) Functional outcome assessments and the impact of pain on daily activities; and (5) Factors predicting physical disability and limitations in daily activities caused by chronic pain.

MATERIALS AND METHODS

Study design and participants

This cross-sectional study included 160 patients with CMP, comprising 30 males and 130 females. The patients were recruited between 2022 and 2024 from specialized outpatient clinics at Assiut University Hospitals in Assiut, Egypt, including Rheumatology, Neurology, and Orthopedics. Each clinic catered to a specific subset of chronic pain patients and offered comprehensive clinical, laboratory, and imaging assessments. Patients often visited multiple clinics and received multidisciplinary evaluations. A multimodal recruitment strategy was employed to ensure a representative sample and minimize selection bias. This is accomplished through: (1) Collaborative work between clinicians and active referrals from these clinics (doctor-as-recruiter model); (2) Consecutive regular recruitment, inviting all eligible patients presenting at the clinics during a specific timeframe to participate in the study; and (3) Managing the consent process and patient screening by the research coordinators (authors).

Inclusion criteria: (1) Adults aged 18–65 years; (2) Presence of persistent musculoskeletal pain for ≥ 3 months; (3) Presence of clear definition of affected area (s); (4) Presence of disproportionate symptoms with negative laboratory and imaging findings. Diagnosis of non-rheumatic musculoskeletal pain was made by experienced rheumatologists, while orthopedic specialists identified patients with chronic non-specific pain and ruled out the need for surgical intervention. Neurologists focused on patients with “functional neurological symptoms” or atypical pain patterns; and (5) Diagnosis of psychogenic CMP was according to the criteria of the International Association for the Study of Pain[25] which is aligned with DSM-5 criteria for SSD with predominant pain[9]. Fibromyalgia was diagnosed based on American College of Rheumatology criteria[26].

Exclusion criteria: (1) Patients with systemic inflammatory or autoimmune diseases (e.g., rheumatoid arthritis, ankylosing spondylitis, lupus, etc.); (2) Individuals with confirmed significant medical or surgical abnormalities (e.g., herniated discs with radiculopathy, spinal stenosis, high-grade spondylolisthesis, vertebral fractures, spinal infections such as discitis, inflammatory arthritides, axial spondyloarthritis, etc.); (3) Presence of neurological signs indicating somatosensory neuropathic pain (as loss of deep tendon reflexes, dermatomal sensory loss, specific muscle weakness or wasting, electromyography evidence of denervation, etc.) or structural cause of central neuropathic pain which was also evidenced by neuroimaging; (4) Patients with primary psychiatric disorders (e.g., schizophrenia, active psychosis, bipolar mania, substance use disorders, etc.); (5) Other medical conditions such as vasculitis, nutritional imbalances, active malignancy, etc.; (6) Presence of recent acute trauma as any major fracture, surgery, or significant tissue injury within the last 6 months that could still be in the biological healing phase; (7) Pregnancy: Due to hormonal and mechanical changes that temporarily alter musculoskeletal dynamics and cause transient musculoskeletal pain; and (8) Cognitive impairment: As this can result in inability to understand the nature of the study and provide informed consent.

Data collection and procedures

All participants underwent detailed medical, rheumatologic, neurologic, and psychiatric histories and examinations (direct interviewing). Data collection was multidimensional to capture the biopsychosocial nature of the condition.

Demographics: Including age, gender, residence, socioeconomic status (SES), marital status, and body mass index (BMI). The Socio-Economic Scale, with a total scoring of 30, was used to assess SES, categorized as high, middle, low, or very low[27].

Pain assessment variables: Including the duration, severity, location, description, patterns, triggering and aggravating factors, investigations, pain relief interventions, impact of treatments, and interference with daily activities due to pain. Pain severity was measured using the Visual Analog Scale (VAS) questionnaire on a scale of 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. Pain intensity was categorized as none to very mild (0-2 points), mild (3-5 points), moderate (5-7 points), and severe/very severe (8-10 points)[28].

Psychiatric assessment: The diagnosis of a psychiatric disorder was done (by psychiatrist, Fawzy M) according to the Structured Clinical Interviewing using Arabic version of DSM-5. Assessment also involved validated questionnaires and tools including the Depression, Anxiety, and Stress Scale (DASS-21), Insomnia Severity Index (ISI), Fatigue Severity Scale (FSS), identification of psychosocial or life stressors and Brief Cope Inventory.

The DASS-21 measures behavioral and emotional symptoms related to depression, anxiety, and stress experienced in the past weeks. The scale comprises of 21 items and can be completed in 3-5 minutes. Specific items pertain to depression (items: 3, 5, 10, 13, 16, 17 and 21), anxiety (items: 2, 4, 7, 9, 15, 19 and 20), and stress (items: 1, 6, 8, 11, 12, 14 and 18). Each item offers four response options: Never or 0 points, sometimes or 1 point, often or 2 points, and almost always or 3 points. Severity levels are classified as normal (0-9), mild (10-13), moderate (14-20), severe (21-27), and extremely severe ( ≥ 28) for depression; normal (0-7), mild (8-9), moderate (10-14), severe (15-19), and extremely severe (≥ 20) for anxiety; and normal (0-14), mild (15-18), moderate (19-25), severe (26-33) and extremely severe (≥ 34) for stress[29].

ISI is a 7-item questionnaire that evaluates the type, severity, and impact of insomnia experienced in the past weeks. Each item is rated on a 5-point Likert scale ranging from 0 (no problem) to 4 (very severe problem). The questionnaire covers various aspects of insomnia, such as difficulty falling asleep, staying asleep, waking up early, dissatisfaction with sleep, interference with daily activities, visibility to others, and distress caused by sleep issues. The total score can range from 0 to 28, with classifications of absence of insomnia (0–7), sub-threshold insomnia (8-14) and clinically significant insomnia [moderate insomnia (15-21), and severe insomnia (22-28)][30].

The FSS is a nine-item tool. It assesses how fatigue affects daily activities such as motivation, physical activity, work, family, and social life. Respondents rate their agreement with statements about fatigue on a Likert scale from 1 “completely disagree” to 7 “completely agree”. Fatigue severity is categorized as normal (< 22), mild-to-moderate (22-34), and severe (≥ 35)[31].

Life stressors questionnaire: A questionnaire was created to pinpoint life stressors linked to the development of CMP. Life stressors were described as significant and unwanted major life events or conditions with a clear beginning and end. Typical stressors in the population were grouped into financial problems, marital difficulties, issues with siblings, changes in personal home activities, changes in work activities, legal troubles, and problems involving close relatives or friends[27].

The Brief Cope Inventory was utilized to evaluate both functional and dysfunctional coping responses to pain as a stressor. It encompasses 14 dimensions, such as self-distraction, active coping, denial, substance abuse, emotional support, behavioral disengagement, venting, instrumental support, positive reframing, humor, religion, acceptance, self-blame, and planning[32]. These coping strategies have been further categorized into adaptive and maladaptive groups based on different models proposed by various authors[33-35]. Each dimension comprises two items and is assessed on a 4-point Likert scale: “I haven’t been doing this at all” (1), “I have been doing this a little bit” (2), “I have been doing this a medium amount” (3), and “I have been doing this a lot” (4). Many authors have argued against the idea of a dominant coping style for any individual.

The World Health Organization quality of life (WHOQOL)-BREF questionnaire comprises 24 questions divided into four domains: Physical, psychological, social, and environmental. These domains evaluate different aspects of participants’ lives and offer a glimpse into their overall health-related quality of life (QOL). Domain scores were computed by adding up individual question scores and converting them to a 0-100 scale. WHOQOL-BREF is a cross-culturally validated instrument. Researchers and clinicians frequently seek a simple “binary classification “or “cut-off point” to distinguish between “normal” and “poor” QOL based on the mathematical midpoint of the scale. On the 0-100 transformed scale, this corresponds to a score of 50 as follow: Low QOL: Scores < 50 and normal QOL: Scores ≥ 50. In this research, scores equal to or greater than 50 indicate a normal health-related QOL in each domain, while lower scores indicate the opposite[36].

Laboratory investigations and imaging: Blood samples were collected between 8:00-10:00 am after an overnight fast for standard laboratory tests, which included a complete blood count, serum creatinine, liver enzymes, glycated hemoglobin A1c, and thyroid stimulating hormone. Additionally, tests for erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and antinuclear antibodies were conducted. Imaging studies such as X-rays and MRI of joints or spine were performed for patients experiencing localized pain if not previously completed. A review of previously conducted investigations was also undertaken.

Statistical analysis

The analysis was conducted using Statistical Package for the Social Sciences (SPSS), version 21.0 (IBM, Armonk, NY, United States). Prior to analysis, the data were checked for outliers, skewness, and homogeneity of variance. Categorical data were reported as n (%), while continuous data were presented as mean ± SD for normally distributed data and median (minimum-maximum) for non-normally distributed data. Comparative statistics included t-tests or one-way analysis of variance (ANOVA) for continuous variables and the χ² test or Fisher’s exact test for categorical variables, with Bonferroni corrections for post hoc analysis. Correlations were assessed using Spearman’s correlation coefficient. A multiple linear regression analysis was performed to explore the relationship between the scores of the physical domain of WHOQOL (dependent variable) and various independent variables. Independent variables comprised demographics (age, gender, marital status, socioeconomic status, residence, and BMI), clinical pain characteristics (duration and severity), and psychosocial domains of WHOQOL (psychological, social, and environmental). The linear regression analysis provided regression coefficients estimates, confidence intervals (at a 95% level), and model fit indicators. The Durbin-Watson test was used to assess the independence of residuals. Model fit was evaluated based on the model summary table, which included R, R2, adjusted R2, standard error of the estimate, and the F-ratio from the ANOVA table. The estimated model coefficients table displayed unstandardized coefficients (B) with standard errors, standardized coefficients (β), t-values, P-values, and 95%CI for β (lower and upper bounds). A significance level of P < 0.05 (two-tailed) was considered statistically significant for all tests.

RESULTS

Demographics

This cross-sectional study involved 160 patients with CMP, with a male to female ratio of 1:4.3. The mean age of participants was 46.63 ± 6.23 years (range: 20-60 year), with 56.25% being married, of middle/high socioeconomic status, and residing in rural areas (62.5%). The majority fell within the age range of 41 years old to 50 years old (53.75%). A BMI ≥ 30 was reported in 25% (n = 45) of the participants. The occupations of the participants were predominantly housewives for females (85%, n = 110) and labor workers for males (100%, n = 30), involving a wide range of physical demands. Comorbid medical conditions included iron deficiency anemia (IDA) (40%, n = 64) which was treated with iron supplements and hypothyroidism (16.88%, n = 27) which was controlled on levothyroxine (Table 1).

Table 1 Demographic and treatment trials’ characteristics of the studied patients, n (%)/mean ± SD.

Demographics	Patients (n = 160)
Gender
Male	30 (18.75)
Female	130 (81.25)
Age (years)	46.63 ± 6.23
Range	20-60
Age groups
20-30 years	13 (18.13)
31-40 years	26 (16.25)
41-50 years	86 (53.75)
51-60 years	35 (21.88)
Marital status
Single	20 (12.5)
Married	90 (56.25)
Widow	30 (18.75)
Divorced	20 (12.5)
Residence
Rural	100 (62.5)
Urban	60 (37.5)
Socioeconomic status
Middle	110 (68.75)
High	50 (31.25)
Body mass index
Normal	60 (37.5)
Overweight	60 (37.5)
Obese	40 (25)
Occupation1
For males (n = 30)
Labor work	30 (100)
For females (n = 130)
Housewife	110 (84.62)
Worker	20 (15.38)
Comorbid medical conditions
Iron deficiency anemia	64 (40)
Hypothyroidism	27 (16.88)
Treatment trials to relief pain
Pharmacological
NSAIDs	160 (100)
Muscle relaxants	25 (15.63)
Systemic steroids	60 (37.5)
Local steroids/anesthetics	20 (12.5)
Antidepressants	90 (56.25)
Antiepileptic drugs	60 (18.75)
Sleep inducing medications	75 (46.88)
Substance abuse	20 (66.67)
Non-pharmacological
Physiotherapy	45 (28.13)
Acupuncture	30 (15.63)
Folk remedies	90 (56)
Psychotherapy	0

¹Percentages were calculated in relation to gender.

NSAIDs: Non-steroidal anti-inflammatory drugs.

Pain characteristics

The mean duration of pain was 16.28 ± 3.05 months (Figure 1A), with the majority reporting moderately severe pain (71.88%, n = 115) and 28.13% (n = 45) experiencing severe/very severe pain (Figure 1B). Continuous pain was reported by 28.13% (n = 45) of the participants, while 71.88% (n = 115) experienced periodic pain. Localized pain was more common (78%, n = 125) than diffuse (fibromyalgia) (about 22%, n = 35), with lower back pain (LBP) being the most frequent localized pain (30.4% or 38/125) (Figure 1C). Fibromyalgia was reported only in females. In patients with fibromyalgia, tender points were identified in various areas including the neck, shoulders, upper chest, elbows, lower back, hips, and knees. Most (72% or 90/125) experienced similar pain in the past but of minor manifestations and did not require hospital admissions. Patients provided various description of pain including aching, tightness, burning, stabbing, tingling, and itching (Figure 1D and E). Pharmacological treatments for pain included: (1) Non-steroidal anti-inflammatory drugs (NSAIDs) such as acetaminophen, diclofenac, ibuprofen, and naproxen sodium; (2) Muscle relaxants like tizanidine, cyclobenzaprine, or thiocolchicoside, and lioresal; (3) Systemic steroids like intramuscular injections of betamethasone and dexamethasone or oral prednisone; (4) Local injections of steroids, and local application of NSAIDs like diclofenac or anesthetics like lidocaine patches; (5) Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) like fluoxetine or serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine and minlacepram; (6) Antiepileptic medications like pregabalin and gabapentin; (7) Sleep-inducing medications like diphenhydramine and eszopiclone; and (8) Opioid specifically tramadol (a centrally acting synthetic opioid analgesic and SNRI). It was reported in about two-thirds of males with CMP. Non-pharmacological interventions included: (1) Physiotherapy (massage, exercises, low-level laser therapy, or ultrasound therapy); (2) Acupuncture; and (3) Folk remedies, such as indigenous plant oils for rubbing areas of pain (e.g., black seed or nigella sativa, camphor, and menthol oils) and both dry and wet cupping. Psychotherapy was not utilized (Table 1). Approximately 28% (n = 45) of the patients were on continuous treatment for at least 3 months, while 25% (n = 40) discontinued treatment due to inefficacy. None reported worsening of pain with any treatment, and 46.88% (n = 75) did not receive regular medical treatment.

Figure 1 Clinical characteristics of chronic musculoskeletal pain. A: Duration of pain ranged from 6 months to more than 6 months; B: Pattern of pain was either continuous or episodic; C: Severity of pain was either moderate or severe/very severe; D: Distribution of pain was either diffuse (fibromyalgia) or localized; E: Description of pain varied among patients. LBP: Lower back pain.

Results of psychiatric evaluation

A review of the participants’ previous consultations and medication history revealed that around 30% had been prescribed psychotropic medications (anxiolytics and antidepressants) within the past two years prior to their current presentation. However, none of them had followed the medication regimen for more than one month. Psychiatric evaluation during the study period revealed that 37.5% (n = 60) of patients had major depression and 43.75% (n = 70) had non-specific anxiety disorder. Patients reported high scores and frequencies of depression, anxiety, and stress symptoms (Table 2). Associated somatic manifestations included poor concentration, memory deficits, headache, shortness of breath, chest tightness, gastrointestinal symptoms (nausea, gaseous abdominal distension, abdominal colic, diarrhea, or constipation), dizziness, tinnitus (unilateral or bilateral), genitourinary symptoms (suprapubic pain and increased frequency of urination), and generalized itching (Figure 2A). Clinically significant insomnia was reported in 87.5% of patients (Figure 2B). Mild and moderate fatigue was reported in 18.6% of patients. It was reported in females with fibromyalgia (Table 2).

Figure 2 The associated somatic manifestations, severity of insomnia and psychosocial stressors. A: Somatic manifestations of pain were multiple; B: Severity of insomnia was mostly moderately severe and severe clinical insomnia; C: Social stressor were multiple and cumulative. GIT: Gastrointestinal tract.

Table 2 Results of psychiatric evaluation, n (%)/range/mean ± SD.

Psychiatric manifestations	Patients (n = 160)
Comorbid psychiatric disorders
Non-specific anxiety disorder	70 (43.75)
Major depression	60 (37.5)
Family history of primary chronic pain
Family history of psychiatric disorders	30 (18.75)
DASS-21
Depression
Mild (score: 10-13)	45 (28.13)
Moderate (score: 14-20)	40 (25)
Severe (score: 21-27)	55 (34.48)
Extremely severe (score: 28+)	20 (12.5)
Score	26.35 ± 2.40
Anxiety
Mild (score: 8-9)	20 (12.5)
Moderate (score: 10-14)	40 (25)
Severe (score: 15-19)	50 (31.25)
Extremely severe (score: 20+)	35 (21.88)
Score	16.83 ± 2.56
Stress
Mild (score: 15-18)	22 (13.75)
Moderate (score: 19-25)	55 (34.38)
Severe (score: 26-33)	60 (37.5)
Extremely severe (score: 34+)	23 (14.38)
Score	36.50 ± 2.83
ISI score	24.53 ± 2.60
Type of insomnia according to ISI
Sub-threshold insomnia	20 (12.5)
Moderately severe clinical insomnia	65 (40.63)
Severe clinical insomnia	75 (46.88)
Non-clinically significant insomnia	20 (12.5)
Clinically significant insomnia	140 (87.5)
Severity of fatigue
Mild-to-moderate (22-34)	30 (18.57)
Maladaptive copying
Self-blame	104 (65)
Behavioral disengagement	64 (40)
Self-distraction or mental disengagement	64 (40)
Denial	30 (18.75)
Substance use	20 (12.5)
Substance abuse1	20 (66.67)
Adaptive copying
Religion	72 (45)
Positive reframing	30 (18.75)
Active coping	30 (18.75)
Emotional support	24 (15)
Venting	24 (15)
WHOQOL-BREF
Physical	20-60 (32.45 ± 12.64)
Psychological	20-60 (38.32 ± 10.46)
Social domains	10-40 (18.20 ± 6.20)
Environmental domains	40-75 (60.42 ± 10.26)

¹Percentages was calculated from male participants.

WHOQOL: World Health Organization quality of life; ISI: Insomnia Severity Index; DASS-21: Depression, Anxiety, and Stress Scale.

During the study period, patients frequently reported life stressors, with financial and work issues affecting 75%, marital problems affecting 60%, and issues with siblings affecting 60%. These stressors were often chronic or cumulative. Personal changes were reported by 40% of patients, while work-home activity issues were reported by 32.5% (Figure 2C). Financial and work stressors included insufficient income, high-pressure work environments, lack of autonomy, and interpersonal distress. Coping responses to pain revealed that many patients were using maladaptive strategies such as self-blame (65%), denial (40%) and behavioral disengagement (40%). Substance abuse (opioids) was more common among male patients (66.67% or 20/30). Religion was the most frequently used positive coping (Table 2).

Results from the WHOQOL-BREF questionnaire indicated lower scores in the physical (32.45 ± 12.64), psychological (mean 38.32 ± 10.46), and social domains (18.20 ± 6.20) compared to the environmental domain (mean 60.42 ± 10.26) (P < 0.0001) (Table 1). Participants reported limitations in daily activities due to pain, reduced work capacity, and the need for medicinal drugs (typically NSAIDs or pain relief medications) to complete tasks. They also experienced mobility issues, insomnia, and dissatisfaction with their health-related QOL. Females with fibromyalgia experienced daily fatigue which hindered physical activities. Additionally, they expressed feelings of meaninglessness, negativity, despair, dissatisfaction with their appearance, low self-esteem, brain fog, and difficulty concentrating. Many believed that there were no effective treatments for their pain. The majority reported dissatisfaction with their sexual life and lack of support from family and friends. Most (80%) were dissatisfied with their leisure activities. Most (85%) could afford health services.

Results of comparative statistics

Apart from females with fibromyalgia, no significant differences had been identified in physical domain of WHOQOL in relation to age (≤ 40 years old vs > 40 years old), marital status (married vs not married including widows and divorced), socioeconomic status (moderate vs high), residence (urban vs rural) and duration and severity of pain. There were no differences in the frequencies of localized pain between males and females with CMP. Comparative statistics in psychiatric parameters between patients with localized vs diffuse CMP showed that patients with fibromyalgia had higher scores of depression (P < 0.01) but not stress and anxiety, and higher scores of insomnia (P < 0.001). There was no significant difference in the frequencies of fatigue in relation to gender. No significant differences had been identified in scores of psychological, social and environmental WHOQOL domains in relation to gender.

Results of correlation analysis

Significant positive correlations were identified between scores of stress, depression (P < 0.001) and anxiety (P < 0.001) symptoms and between stress and anxiety (P < 0.001) symptoms; between scores of ISI and stress (P < 0.001), depression (P < 0.001) and anxiety (P < 0.001); between fatigue and stress (P < 0.001), depression (P < 0.001), anxiety (P < 0.001) and insomnia (P < 0.001). The psychological domain showed a significant positive association with the other three WHOQOL domains [physical (r = 0.318, P < 0.05), social (r = 0.338, P < 0.05), and environmental (r = 0.206, P < 0.05)].

Results of multiple linear regression analysis

It showed that factors associated with low physical domain of WHOQOL (after controlling of gender, age, socioeconomic status, residence, marital status and BMI) included duration of pain (β = 1.426; 95%CI: 0.565-3.428; P < 0.01), symptoms of depression (β = 2.356; 95%CI: 1.564-4.842; P < 0.01), anxiety (β = 1.232; 95%CI: 0.863-4.680; P < 0.01) and stress (β = 2.346; 95%CI: 1.620-6.550; P < 0.001), insomnia (β = 1.843; 95%CI: 1.648-3.642; P < 0.01), low psychological (β = 6.7; 95%CI: 2.30-8.640, P < 0.001) and social domains (β = 3.5; 95%CI: 5-12, P < 0.001) of WHOQOL.

DISCUSSION

This study focused on patients with psychogenic CMP. They were predominantly females in their 30s and 40s and married. Most participants had physically demanding jobs or household responsibilities. The patients reported pain that varied in location and intensity, with occasional flare-ups (72%). In this study, localized musculoskeletal pain was frequently reported compared to diffuse. LBP was the most common localized pain, affecting 30.4% (38 out of 125) of individuals. There were no significant differences in pain frequency based on demographic variables. LBP is the second leading cause of disability in the United States, with over 80% of people experiencing it at some point in their lives[37]. Common causes of LBP include disc injuries, sciatica, heavy lifting, or non-specific back injuries. In this study, none of the patients had abnormal neuroimaging. Most patients with localized pain described pain in areas previously injured or affected by minor issues, without requiring specific interventions or hospitalizations[37].

In this study, fibromyalgia was only reported in females (23% or 30 out of 130). Studies have shown a higher prevalence of fibromyalgia in females, estimated at 3.98% (2.8%-5.2%) compared to 0.01% in males. The incidence was 7-9 times higher in females than in males. Females with fibromyalgia typically exhibit a broader range of symptoms (61% to 90%)[2,3,14]. The higher frequency of CMP (diffuse/Localized) in females compared to males may be attributed to various factors: (1) Cultural influences may play a role, as women might tend to overstate their pain to justify their suffering, while men may tend to minimize it[24]. Females commonly use complaints as a form of emotional expression or seeking attention, as a defense mechanism in perceived threatening situations, or due to dominant personality traits[38]; (2) Females with lower educational attainment and those living in rural or nonmetropolitan areas commonly experience a higher burden of chronic pain[39]; and (3) Studies have noted the influences of sex hormones on different brain areas, receptors, spinal neurotransmitters, neuromodulators, and the HPA axis. Research has shown that estrogen can modulate the density of opioid receptors and the sensitivity of the ACC[40].

Screening patients for comorbid medical and psychological conditions and disorders revealed that only a few had conditions such as IDA[41] or hypothyroidism[42], which were identified early before the onset of pain and managed with medications. Previous studies have shown varying results regarding the prevalence of comorbid medical conditions in patients with CMP, compared to the general population. Many studies have reported no significant difference, while others have found higher frequencies of medical comorbidities such as endocrine diseases like diabetes mellitus, thyroid and adrenal diseases[41,42] in patients with fibromyalgia.

In this study, we found high rates of stress, depression, anxiety symptoms, and insomnia among patients with CMP. Major depression was reported in 37% of patients, and anxiety disorders in 44%. Patients with fibromyalgia had higher scores of depressive symptoms compared to those with localized pain and all reported fatigue. Studies reported higher rates of generalized anxiety disorder, panic attack, phobias (20%-80%)[7,43], obsessive compulsive disorder (1.1% to 8%), post-traumatic stress disorder (about 40%)[7,44], major depressive disorder (13%-63.8%)[7,43] and bipolar disorders (approximately 24%)[45] in patients with fibromyalgia compared to general population. Fatigue was pronominally reported in females with fibromyalgia[46].

In this study, insomnia was particularly common, affecting nearly 88% of patients, compared to only one-quarter of the general population[47]. The relationship between chronic pain and sleep disturbances is often bidirectional: Chronic pain disrupts sleep patterns, while poor sleep lowers the pain threshold and impairs the body’s natural pain management mechanisms, leading to a cycle of exhaustion and pain[48]. Additionally, patients experienced various somatic symptoms such as poor concentration, headaches, chest tightness, gastrointestinal issues, dizziness, tinnitus, genitourinary problems, and generalized itching. Previous studies indicated a biological bidirectional relationship between CMP and mental issues[6,7]. Pain complaints, especially neck and back pain, are often intensified in individuals with depression, and changes in pain levels can predict the severity of depression and vice versa[7,13,43]. In central sensitization and SSD, it has been shown that the brain’s perception of pain is influenced by emotional states, and persistent physical pain can impact mental health. Neuroimaging studies have revealed overlapping brain regions involved in both conditions, such as the amygdala, ACC, and prefrontal cortex. Patients with CMP often exhibit hyperactivation of the perigenual ACC, which is linked to the dopamine system and reward processing[49]. This suggests that chronic pain can affect the brain’s emotional circuitry, leading to anhedonia and an increased risk of clinical depression. The dysregulation of neurotransmitters like serotonin and norepinephrine plays a role in the overlap between pain and depression, affecting mood modulation and pain signal inhibition[50].

Many participants in the study reported experiencing life stressors before the onset of pain, with some facing chronic or cumulative major stressors like financial difficulties, marital problems, and issues with siblings. Life stressors can range from significant life changes to daily pressures and can be current or historical. The connection between life stress and chronic or psychogenic musculoskeletal pain is intricate and profound, with stress serving as both a catalyst for acute pain and a contributor to its persistence (chronification). Prolonged stress leads the body into a continuous state of “fight-or-flight”, causing sustained muscle tension, lowered pain thresholds, and chronic low-grade inflammation[51]. Studies reported that childhood and adolescent traumas have been associated with the severity of disability in CMP[52]. They also reported that external elements such as weather, temperature, humidity, rest, exercise, and noise can also impact psychogenic pain[53].

The study revealed that patients often relied on pain relief and anti-inflammatory medications to manage their pain, with occasional use of other treatment methods. Analysis of patients’ past consultations and prescriptions showed that about 30% had been prescribed psychotropic medications for depression or anxiety prior to experiencing pain but none continue treatment for more than a month[9,12,15]. Studies indicate that 30%-65% of individuals with chronic, complex conditions or severe mental illnesses fail to adhere to their medication regimen, resulting in worsened symptoms, decreased treatment efficacy, and increased risk of relapse. In the case of pain management, patients frequently discontinue antidepressants due to a lack of immediate relief from physical pain or a belief that the medication is unnecessary, especially if they are not fully convinced of the psychological origins of their pain[54]. Studies also have shown that chronic pain can complicate the therapeutic response to SSRIs such as sertraline and escitalopram, especially in patients with both pain and depression compared to those with depression alone[55]. Some male patients used opioids for pain relief[8], while none had undergone psychotherapy. Many patients also tried folk remedies for pain relief[56]. During the study, approximately half of the patients reported either discontinuing medications or using them sporadically. They held beliefs such as the lack of effective treatment, the seriousness of their illness, the expectation of worsening symptoms, and the perception that their condition was disabling and unlikely to improve with treatment. Previous research suggests that in some patients with chronic pain, pharmacological treatment alone may not be sufficient for CMP and should be complemented with other therapies like physical exercise and psychotherapy[55,57,58].

Coping strategies were found to play a crucial role in how pain is perceived and its impact on daily activities and also indirectly influence depression and can affect social and family support. In this study, negative coping mechanisms such as self-blame, denial, and physical and mental disengagement and substance abuse were prevalent responses to pain. Patients with diffuse pain exhibited a higher frequency of negative coping compared to those with localized pain. Religious coping emerged as the most commonly used positive coping strategy among the patients studied. Studies reported that the negative coping mechanisms with CMP include fear-avoidance behavior, behavioral overactivity in response to pain, catastrophizing the effects of pain, and low self-compassion and self-efficacy. They also indicated that pain modulation is influenced by personality traits, psychological factors, and cognitive distortions[59-62]. In fear-avoidance behavior, individuals interpret pain as a sign of structural damage and avoid certain movements or activities. This can perpetuate the cycle of pain maintenance, result in physical deconditioning, and therefore increased central sensitization[59]. Behavioral overactivity in response to minor pain and dysfunctional persistence can also lead to increased functional limitations[60]. Catastrophizing the effects of pain involves an exaggerated negative orientation toward pain. This is characterized by worrying, rumination, magnification of pain threats, distracting and distressing thoughts and feelings of helplessness[61]. Studies have shown that pain catastrophizing is associated with increased activity in the ACC and amygdala, indicating that thoughts about pain can activate the same neural circuits as the sensation of pain[63]. In this study, two thirds of males used opioids to relief pain but none received the diagnosis of substance abuse disorder. Studies have identified a phenomenon called “adverse selection,” where patients with mental health comorbidities are more likely to receive higher doses of opioids, potentially exacerbating depression over time due to a “long-term usage” effect[8].

In this study, the functional outcome was evaluated using WHOQOL questionnaire. In patients with CMP, assessments of WHOQOL focus on how musculoskeletal pain impacts different dimensions of their lives, including physical, psychological, social, and environmental aspects. These assessments are essential for evaluating treatment effectiveness and shaping healthcare policies to improve population health. The WHOQOL questionnaire results showed lower scores in all domains. Participants mentioned limitations in daily activities due to pain, reduced work capacity, and reliance on medicinal drugs like NSAIDs for task completion. They also experienced daily fatigue, insomnia, and dissatisfaction with their health-related QOL. Additionally, they expressed feelings of meaninglessness, negativity, despair, dissatisfaction with appearance, low self-esteem, brain fog, and difficulty concentrating. Many felt there were no effective treatments for their pain, and most were dissatisfied with their sexual life and lack of support from family and friends. Studies have shown that in patients with CMP, low family and social support may be linked to depression[64]. Regression analysis showed that predictors for lower physical domain of WHOQOL included duration of pain, depression, anxiety, stress and insomnia, lower psychological and social domains of WHOQOL. Studies reported that pain can directly contribute to depression and psychological distress and depressive symptoms can exacerbate pain and increase disability associated with musculoskeletal pain[65].

Results of this study indicate that the psychopathological mechanisms of CMP include various factors. Life stressors can predispose individuals to both CMP and mood/anxiety disorders, affecting pain perception and daily functioning. Patients may experience limitations in activities, work, and somatic distress due to chronic illness. Also, WHOQOL and daily activity levels are influenced by psychological perceptions of pain, social factors, and coping mechanisms. Therefore, it is recommended that future treatment plans should incorporate physical, psychological, and psychopharmacotherapy interventions. Physiotherapy interventions may involve reducing bed rest, gradual stretching, strengthening and aerobic conditioning. Psychological and behavioral treatments include Cognitive-Behavioral Therapy (CBT), Mindfulness-Based Stress Reduction (MBSR), and Acceptance and Commitment Therapy (ACT). These therapies aim to reduce catastrophizing, enhance emotional awareness, and impact the neurobiological mechanisms of pain perception. CBT helps patients reframe catastrophic thoughts, while MBSR and ACT focus on mindfulness and psychological flexibility, respectively[66-68]. These plans should be culturally sensitive and financially accessible, utilizing community-based resources or telehealth. Also, longitudinal studies are necessary to examine a large sample size from both genders to identify risk factors for CMP. Randomized controlled trials are needed to assess changes in pain levels after manipulating psychological variables over time.

To summarize, we assessed a wide range of patients with CMP in a general health practice, without exclusions based on the type, duration, severity, or location of CMP. In this study, validated and reliable questionnaires were used, and a thorough amount of data was collected to provide a detailed description of pain and mental health characteristics. The goal was to determine the overall burden of symptoms in this population. This study provides insights into significant mental health concerns that need attention in CMP patients. However, this study has limitations. Firstly, the cross-sectional study design presents challenges in establishing a clear temporal sequence between the predictor and the outcome. This is known as “reverse causality”. It is possible that low physical activity could precede the development of psychogenic pain, or chronic pain itself may have led to a decline in physical QOL. Additionally, the cross-sectional design does not account for the fluctuating nature of CMP. Secondly, the small sample size of 160 patients, while adequate for basic descriptive statistics, may be relatively insufficient when subgrouping patients according to different variables, leading to statistically type II error (i.e., failing to detect a real effect). Moreover, recruitment from specialized clinics in a tertiary referral hospital may introduce a selection bias towards severe cases with higher rates of both pain and psychological comorbidity, limiting the generalizability of the results to the general population. Furthermore, the notable gender imbalance in the sample, with ~80% of participants being female. While CMP and psychogenic disorders are more common in women, such a skewed ratio may limit the generalizability of the results to males.

CONCLUSION

CMP is a common condition that primarily affects middle-aged individuals, particularly females. Localized pain is more prevalent than diffuse pain. People with CMP often experience high levels of stress, depression, anxiety, insomnia, fatigue, and various physical symptoms, leading to a decline in overall QOL. Factors such as the duration and intensity of musculoskeletal pain, as well as psychological and social factors, are significant predictors of poor physical well-being. CMP is thought to be caused by changes in central brain processing influenced by psychosocial factors. Understanding the link between musculoskeletal issues, prolonged disability, and mental health is crucial for developing effective treatment strategies.