Introduction

Musculoskeletal pain (MP) is common in the general population. Studies have reported a MP prevalence varying from 15% to 47% [1–4] and a chronic widespread pain (CWP) prevalence varying between 11.4% and 24% [4].

Although the definition of MP remains uncertain, Woolf and Pfleger [5] defined musculoskeletal conditions as “a diverse group with regard to pathophysiology but which are linked anatomically and by their association with pain and impaired physical function. They encompass a spectrum of conditions, from those of acute onset and short duration to lifelong disorders.”

In fact, MP covers a wide range of conditions, including osteoarthritis, rheumatoid arthritis, osteoporosis, low back pain, fibromyalgia, and primary or secondary headaches. It can be widespread or regionalized and could affect all of the body, predominantly the neck, lower back, shoulders, elbows, knees, and fingers. According to Carnes et al [6], more than 75% of patients have pain in multiple sites instead of a single site.

Evidence [4, 6] shows that MP has the following risk factors: age, gender, smoking, low education, low physical activity, poor social interaction, low family income, depression, anxiety, sleep disorders, psychological distress, performing manual work, being a recent immigrant, being non-Caucasian, and not married.

MP seems to have a great impact on physical and mental health problems and, therefore, may significantly affect quality of life. Some surveys [5] point to a 5% prevalence of physical disabilities caused by a musculoskeletal condition in the general population with a huge societal impact such as work disability and utilization of health care services.

Mental health problems such as depression and anxiety seem to have a great impact on the prevalence and also the disability of MP.

Anxiety disorder is a very common condition with an estimated lifetime prevalence averaging approximately 16% [7]. These anxiety aspects have been linked to MP in several ways:

  1. (a)

    Muscle tension is included as a part of the diagnostic criteria for generalized anxiety disorder (GAD) according to the DSM IV [8]

  2. (b)

    Pain can be a common symptom and a good indicator of an anxiety disorder, particularly GAD [9]

  3. (c)

    Anxiety is an independent predictor of quality of life in patients with chronic MP [10]

  4. (d)

    Anxiety leads to higher levels of chronification [11], more severe pain, and long-lasting attacks in migraine patients

  5. (e)

    Fear, anxiety, and avoidance are related to MP [12].

Symptoms such as muscle tension, body soreness, and headaches are common not only in anxiety patients but also in some conditions such as fibromyalgia [13] and migraine [11, 14]. All these disorders seem to be somewhat connected. For instance, those who suffer from chronic pain and also have an anxiety disorder may have a lower tolerance for pain [15], people with anxiety disorders may be more worried about their health and more fearful of medication side effects [16], and they may also have lower pain thresholds than those without anxiety [17].

The objective of this article is to explore the mechanisms underlying the relation between anxiety disorders and musculoskeletal pain as well as its management.

Mechanisms of Anxiety and Musculoskeletal Pain

There are many mechanisms proposed for the etiopathology of musculoskeletal pain. Interestingly, some of these factors are overlapped by anxiety and fear. We will discuss some of these overlapping factors.

Genetics

Several studies have reported an association between catechol-O-methyltransferase (COMT) polymorphism, pain sensitivity, and musculoskeletal pain [18, 19]. The same association is verified in anxiety disorders. There is a relation between COMT polymorphism and phobic anxiety, anxiety vulnerability, generalized anxiety disorder, and fear processing [20–22].

Neurotransmitters

The role of neurotransmitters also seems to overlap in both conditions. For instance, lower levels of serotonin have been associated with musculoskeletal pain [23] and also with anxiety [24]. The same seems to happen with dopamine, in which lower levels seem to be associated with MP and anxiety [25, 26].

Stressful Life Events

There is a relationship between stressful life events, anxiety, and also MP [27, 28].

Sex

Women seem to be more vulnerable and to have a higher prevalence of MP, fear, and anxiety [29, 30].

Association Between Anxiety, Fear, and Musculoskeletal Pain

Several studies have assessed the connections between anxiety, fear, and musculoskeletal pain.

Gore et al [31] have evaluated 101,294 persons categorized as chronic low back pain patients (CLBPP) and controls. They found that CLBPP have great psychiatric comorbidity, such as depression (13.0% CLBPP vs 6.1% controls), anxiety (10.0% CLBPP vs 3.4% controls ) and sleep disturbances (8.0% CLBPP vs 3.4% controls ). In addition, those with CLBPP also have a greater utilization of health services.

These results seem to persist in all ages. Knook et al [32] found that 21% of their pediatric sample with unexplained chronic pain had psychiatric disorders, predominantly anxiety disorders (18%).

Regarding anxiety and pain outcomes, Asmundson et al [33] have investigated 4 groups of students: (a) those with both high trauma-related stress and social anxiety symptom scores (TRS/SAS), (b) only high trauma-related stress symptom scores (TRS), (c) only high social anxiety symptom scores (SAS), or (d) neither (N). They found that the TRS/SAS group had significantly higher scores on all fear of pain measures, anxiety, sensitivity, and illness/injury sensitivity than any other group.

Greenberg and Burns [34] have evaluated chronic musculoskeletal pain patients who underwent cold pressor and mental arithmetic tasks while cardiovascular, self-report, and behavior indexes were recorded. As a result, they found that the effects of pain anxiety on task responses were accounted for by anxiety sensitivity.

Bair et al [35•] have evaluated 500 patients with chronic musculoskeletal pain. Patients with pain and both depression and anxiety experienced the greatest pain severity and pain-related disability. In addition, patients with psychiatric comorbidity have more disability days.

Similar results were obtained by Carleton et al [36]. They have used the Waddell’s sign to indicate pain-related psychological distress in chronic low back pain patients. As a result, patients with more than 2 of Waddell’s symptoms reported higher levels of depressive symptoms, pain-related anxiety, fear, catastrophizing, and pain intensity. Nevertheless, there were no significant differences in functional capacity.

Beneciuk et al [37] have evaluated the role of pain catastrophizing on pain intensity. They found that pain catastrophizing contributed specifically to evoked pain intensity ratings during neurodynamic testing for the median nerve of healthy subjects.

Jensen et al [38] have studied the role of anxiety in care-seeking for musculoskeletal pain. They found that somatization and health anxiety were associated with seeking care for back pain.

Anxiety seems also to predict lower quality of life in MP patients. Orenius et al [10] found that anxiety at baseline predicted the quality of life of MP patients after one year of follow-up.

Fear-Avoidance Model of Musculoskeletal Pain

Fear is the emotional reaction to a specific, identifiable, and immediate threat [39]. Fear has its nature in protecting the individual from impending danger, promoting a self-defense associated with the ‘fight or flight’ response [40].

Anxiety, in contrast to fear, is a future-oriented affective state and the source of threat is more elusive without a clear focus [41], through hyper vigilance, which occurs when the individual engages in environmental scanning for potential sources of threat.

The components of anxiety are somewhat similar to those of fear, but less intense. Anxiety is associated with preventative behaviors, including avoidance [42]. The distinction between fear and anxiety may not be evident, and these terms are frequently used interchangeably [43].

The fear and anxiety responses can be physiological (increase muscle tension), behavioral (escape and avoidance behavior), as well as cognitive (catastrophizing thoughts). While in pain, patients’ fears and phobias are described, such as fear of pain, fear of work-related activities, fear of movement, and fear of (re)injury. Some authors [44] believe that the pain-related fear could be more disabling than pain itself.

This fear-avoidance model of pain was first described by Lethem et al [45] in 1983 in “the fear-avoidance model of exaggerated pain perception” and proposed as a model for chronic low back pain by Vlaeyen and Linton [12] in 2000 and by Leeuw et al [41] in 2007 (Fig. 1).

Fig. 1
figure 1

The fear-avoidance model of pain (adapted from Leeuw et al. [41])

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The fear-avoidance model consists of nonthreatening acute pain (low fear) and catastrophically (mis)interpreted pain [41]. When nonthreatening acute pain is perceived, patients usually maintain normal activity, and functional recovery is achieved. A vicious cycle is initiated when catastrophically (mis)interpreted pain begins. Some dysfunctional interpretations could lead to pain-related fear, and some safety-seeking behaviors (avoidance/escape and hypervigilance). These fears may be adaptive in the acute pain stage, but may worsen the course of the disorder in the case of long-lasting pain. As a result, disability and disuse may appear and also lower the threshold at which subsequent pain will be experienced.

According to this model, several aspects can impact pain experience; pain severity, pain catastrophizing, attention to pain, avoidance behavior, disuse, and disability. Anxiety sensitivity has been included in the fear-avoidance model as a vulnerability factor to explain individual differences in fear.

The Past-Present-Future Model of Musculoskeletal Pain

Another way to understand the role of anxiety in pain is the proposed “Past-Present-Future model of musculoskeletal pain” (Fig. 2).

Fig. 2
figure 2

The past-present-future model of musculoskeletal pain

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According to this model, considering that sense perception in humans is within the present time, consciousness is experienced as being part of the present, exactly in this moment. Some facts that have already happened could be remembered and some facts that possibly will be happening in the near future could be anticipated by this consciousness (Fig. 2a).

Nevertheless, if a negative life event is re-experienced or there is a negative perspective of a future event, a catastrophizing experience is felt. Therefore, sense perception, brain responses, and the physiological system are ready for releasing defense mechanisms, such as the ‘flight or fight response’. As a result, the individual may re-experience or even anticipate this scenario as a threat, actually happening at the current time (Fig. 2b).

General Treatment for Musculoskeletal Pain

When anxiety disorders are associated with MP, a specific treatment strategy should be planned. Usually 2 complementary strategies could be used: nonpharmacological and pharmacological [46].

Nonpharmacological

First, a good nonpharmacological plan should be performed. Some options available are exercise, physiotherapy, herbal remedies, acupuncture, sensory stimulations, education and behavioral interventions [46, 47].

Pharmacological

Pharmacotherapy is also a key therapeutic option for a comprehensive and successful pain management. According to a recent review [48], there is evidence that tricyclic antidepressants, serotonin reuptake inhibitors, and dual serotonin-norepinephrine reuptake inhibitors are effective for musculoskeletal pain. Some studies suggest that the anti-seizure medications (pregabalin and gabapentin) and the analgesic tramadol are also effective.

Treating Musculoskeletal Pain in Anxiety Patients

In some situations, as reported throughout this article, there is an overlap between anxiety, fear-avoidance, and MP (Figs. 1 and 3). For these patients, some particularities of the treatment will be discussed:

Fig. 3
figure 3

Therapies available for musculoskeletal pain that can also treat anxiety and fear. CBT cognitive-behavioral therapy

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Caffeine Consumption

Patients with anxiety should limit caffeine, which can trigger panic attacks and worsen anxiety symptoms [49]. Excessive intake of caffeine is recognized as an aggravating factor of headaches [50] but not for other pain conditions [51]. Avoiding caffeine late in the day and at night may also help to promote a more efficient sleep [52], which is related to anxiety.

Sleep Patterns

Some studies have shown that a restorative sleep has a pivotal role in pain improvement [53, 54] and anxiety [55]. Bigatti et al [54] found that in their sample, sleep problems predicted pain and pain predicted physical functioning, suggesting a critical role of sleep in fibromyalgia syndrome symptoms.

Physical Exercise

Regular exercise strengthens muscles, reduces stiffness, improves flexibility, and improves mood and self-esteem. Patients with mild disease may have a self-limiting and reversible problem usually helped by encouragement of aerobic-based exercises [56]. In patients with anxiety, exercise seems to reduce anxious symptoms [57] and possibly booster the improvement on musculoskeletal pain.

Cognitive-Behavior Therapy

Cognitive-behavior therapy (CBT) is an effective therapy used to treat anxiety disorders [58] as well as chronic pain conditions [59]. Morley et al [59] found in a systematic review that active psychological treatments such as CBT are effective in chronic pain and can change measures of pain experience, mood/affect, cognitive coping, pain behavior, and social role function. In another recent systematic review, Hofmann and Smits [58] found that CBT is also efficacious for adult anxiety disorders.

Relaxation Techniques

Relaxation techniques can help people develop the ability to cope more effectively with triggers and those causes contributing to anxiety and pain. Common techniques include breathing retraining, progressive muscle relaxation, mindfulness meditation, and biofeedback [60].

Complementary and Alternative Therapies

Some interventions such as acupuncture, qi-gong, and other modalities of hands imposition, yoga, massage, and hydrotherapy seem to help patients through their action in pain [60] and in anxiety reduction [61].

Spirituality and Religiosity

Several studies have shown the impact of spirituality and religious faiths (S/R) on better mental/physical health, higher quality of life, and lower mortality [62–66]. S/R also seems to play a role on the pain process and influence the treatment of pain. Many authors have shown that persons with chronic pain use religious and spiritual beliefs and activities to cope with pain [67, 68••]. Nevertheless, usually this aspect is under-recognized by therapists [62, 69]. Spirituality and pain were investigated in the following studies.

Harrison et al [70] evaluated 50 patients with sickle cell disease and found that higher church attendance was significantly associated with lower scores on pain measures.

Keefe et al [71] have investigated rheumatoid arthritis patients and found that those with higher religious coping and spirituality had higher levels of positive mood, lower levels of daily negative mood, higher levels of social support, and were less likely to have joint pain.

Lucchetti et al [62] have evaluated older adults from an outpatient rehabilitation setting and found that greater self-reported religiousness was associated with lower ratings of pain.

Büssing et al [72] have studied chronic pain patients and found an association between spirituality/religiosity, positive appraisals, and internal adaptive coping strategies.

Baetz and Bowen [73] have investigated 37,000 individuals from ‘The Canadian Community Health Survey’ and found that religious persons were less likely to have chronic pain and fatigue. Individuals with chronic pain and fatigue were more likely to use prayer and seek spiritual support as a coping method than the general population, and chronic pain and fatigue sufferers who were both religious and spiritual were more likely to have better psychological well-being and use positive coping strategies.

S/R also can have an influence on anxiety. Studies have shown that higher levels of positive S/R are associated with lower levels of anxiety [74, 75] and that multifaith spiritually-based intervention can have positive outcomes for generalized anxiety disorder [76]. Nevertheless, negative religious coping strategies are positively associated with negative psychological adjustment to stress. That is, individuals who reported using negative forms of religious coping experienced more depression, anxiety, and distress [68••, 77]. Therefore, there may be a connection between spirituality, religiosity, anxiety, coping, fear, and pain that could have repercussions on the treatment of chronic conditions and musculoskeletal pain. Further studies are needed on this issue.

Pharmacotherapy

For the treatment of musculoskeletal pain, there are several medications that can be used. Some agents such as simple analgesics (acetaminophen and NSAIDs), muscle relaxants (cyclobenzaprine), and opioids (tramadol) are used in specific contexts [48, 78]. Nevertheless, most intermediate treatment options between simple analgesics and opioids have both analgesic and anti-anxiety effects (antidepressants for example). Here, we will discuss drugs that have both effects (Table 1).

Table 1 Treatment efficacya for pain and anxiety
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Tricyclic Antidepressants

Tricyclic antidepressants (amitriptyline, start at 10–25, titrate to 100 mg or nortriptyline, start at 10–25, titrate to 100 mg) are drugs that can be used in almost all musculoskeletal pain conditions such as fibromyalgia [79], osteoarthritis, and low back pain [78]. It is also used in anxiety-depression conditions. Nevertheless, some adverse effects such as dry mouth, weight gain, constipation, and morning drowsiness can happen. In addition, physicians must be cautious when prescribing for elderly patients or those with cardiovascular diseases.

Serotonin–Norepinephrine Reuptake Inhibitors and Selective Serotonin Reuptake Inhibitors

Duloxetine 60 mg daily and milnacipran 50–100 mg bid are serotonin–norepinephrine reuptake inhibitors (SNRIs) used for musculoskeletal pain that can also treat anxiety symptoms. A placebo-controlled trial of duloxetine in patients with depression and moderate-to-severe pain but no organic pain diagnosis found a significant benefit for both pain and depression symptoms [80]. Other drugs such as escitalopram 10–20 mg (selective serotonin reuptake inhibitors [SSRI]) or venlafaxine 37.5–150 mg (SNRI) are also possible options with lower evidence at this moment. These drugs are usually more tolerable than the tricyclic antidepressants. Other antidepressants may also be included in combination; agomelatine has been studied in anxious patients [81] but not well evaluated in pain.

Anticonvulsants

Other drugs such as pregabalin (300–450 mg daily in divided doses) [82] and gabapentin (1200–2400 mg/d) [83] seem to have positive effects, particularly in fibromyalgia.

Conclusions

There is an intrinsic connection between anxiety, fear, and musculoskeletal pain. Studies have shown that patients with anxiety have higher prevalence of musculoskeletal pain and vice-versa. In this review, we found some similarities in proposed mechanisms and explicative models for both conditions as well as an overlapping between the treatments available. The recognition of this association is important for professionals who deal with chronic pain.