Pain Catastrophising in Individuals with Fibromyalgia: A Critical Review, Part Two

PART TWO

Effective Interventions for Pain Catastrophising in Individuals with Fibromyalgia: A Critical Review

Introduction

Affecting about 2-5% of the population worldwide, fibromyalgia is a chronic disorder commonly characterized by widespread musculoskeletal pain (Lami et al., 2018). While the American College of Rheumatology stipulates that unresolved symptoms be present for a minimum of 3 months, many other manifestations including fatigue and cognitive difficulties are also frequently observed, thus complicating diagnostic rigor (Paschali et al., 2021). As the underlying pathophysiology of fibromyalgia is currently unknown and there are no definitive biomarkers, it is often a diagnosis received by process of elimination (Ellingson et al., 2018). Current drug-forward multi-modal treatment plans purport little to no efficacy (Alda et al., 2011). A maladaptive pattern of cognitions, pain catastrophising is the most well-recognized factor in predicting both the chronicity of fibromyalgia as well as future projections (Paschali et al., 2021). This critical review will posit pain catastrophising as a risk factor for fibromyalgia, underscoring its psychosocial and physiological impact as well as exploring the most effective treatment methods for diminishing it. Ethical concerns will also be raised, concerning considerations that must be taken regarding respect, responsibility, and integrity in designing and executing experimental interventions when working with this vulnerable population.

A search was conducted in PUBMED, PsychINFO, and MEDLINE using a combination of medical subject headings (MeSH) and free text search terms. Primary search terms included fibromyalgia, fibromyositis, or fibrosis and catastrophi?ing or catastrophi?ation. A series of searches were conducted using varied secondary terms including cognitive behavio?ral therapy, acceptance and commitment, and mindfulness. Additional articles were included in the review, located via unstructured searches and through reference lists of pertinent studies. Subject populations aged 18 years or older were considered for inclusion and co-morbid psychotic disorders or substance abuse excluded them from further evaluation. All titles and abstracts were analysed, and 39 studies were ultimately selected for inclusion.

Defining Pain Catastrophising

A standard tool utilized across a variety of pain studies, pain catastrophising is most commonly measured via the 13-item Pain Catastrophizing Scale (PCS) as developed by Sullivan et al. (1995). The dysfunctional thought processes of catastrophising are best understood through the three subgroups within the PCS: rumination, magnification, and helplessness (Ellingson et al., 2018). Although the PCS displays high internal reliability and validity as a composite test, structural variation is noted across the subscales when assessed across translated editions suggesting divergent cross-cultural cognitive processes (Ikemoto et al., 2020). While women are more likely to suffer from fibromyalgia and catastrophise than men, they also score consistently higher on rumination and helplessness subscales (Sullivan et al., 1995).

Though catastrophising is a greater predictor than pain in forecasting the long-term impact of fibromyalgia, the relative importance of different subsets of the PCS have been shown to change over time (Campbell et al., 2012). Rodero et al. (2010) found that rumination followed by magnification followed by helplessness best predicts impact as fibromyalgia chronicity sets in. Important in focusing treatment efforts as well as highlighting the importance of early intervention, this knowledge allows for immediate action to be taken before the complexity of the disorder compounds.

Psychosocial Correlates of Catastrophising

Quality of life in those with chronic fibromyalgia was previously thought to be a by-product of pain intensity and sustained disability (Sullivan et al., 1995). However, as some patients suffer elevated levels of pain and report little disability while others report little pain and significantly impacted daily functioning, a missing variable is evident (Richardson et al., 2009). Studies have since shown that catastrophising itself directs the trajectory of a variety of psychosocial variables including quality of life, pain intensity, and disability (Gracely et al., 2004). Analysing numerous methods of self-report, Paschali et al. (2021) found that heightened levels of catastrophising were positively correlated with increased pain levels and served as a strong predictor of poor global functioning. Although Ellingson et al. (2018) did not find catastrophising to be an indication of the magnitude of pain, it was found to have considerable negative impact on quality of life and disability. Unlike self-report measures used by Paschali et al. (2021), relational conclusions were drawn utilizing fMRI by Ellingson et al. (2018). Additionally, subjects in the Paschali et al. (2021) study also reported a mean PCS score of more than double that recorded by subjects in the Ellingson et al. (2018) study. These vast differences in methodologies and severities of catastrophising between the two study populations may have resulted in the disparity in results.

Catastrophising has long been considered as another component of the diverse fibromyalgia phenotype. However, Campbell et al. (2012) found that reductions in catastrophising between pre- to post- assessment periods affected subsequent pain ratings, temporally preceding the presentation of pain. The opposite relationship was not observed, suggesting that catastrophising may occur prior to and modulate the experience of pain (Campbell et al., 2012). This is noteworthy when considering the muted efficacy of pharmaceuticals on managing symptoms as opposed to cognitive-behavioural therapies which have the potential to address the entire pain syndrome, very possibly rooted in dysfunctional cognitions (Alda et al., 2011).

In addition to moderating pain-related concepts, catastrophising has also been shown to regulate co-morbid affective states such as depression and anxiety disorders (Sullivan et al., 1995). An estimated 46% of fibromyalgia patients have been concurrently diagnosed with depression while ranges for co-morbid anxiety disorders vary greatly from 13 to 64% (Pae et al., 2009). In a study by Lami et al. (2018), correlational analyses of self-report measures revealed that catastrophising showed significant positive associations with depression, anxiety, and global fibromyalgia impact and a significant negative correlation with pain acceptance. Richardson et al. (2009) echoed these findings, discovering that catastrophising, but not acceptance, accurately predicted depressive states. In patients with co-morbid fibromyalgia and affective disorders, addressing depression or anxiety directly is likely to serve as a temporary salve for what actually stems from a much larger syndrome. Taken together, these conclusions fortify the utility of catastrophising as a focus of treatment in those with fibromyalgia and co-morbid affective disorders.

Physiological Correlates of Catastrophising

Through modification of neural activity, catastrophising effectively alters the perception of pain at a physiological level as visualized by fMRI. Catastrophising has been linked to increased activity in brain centres devoted to allocation of attentional resources, anticipation of nociceptive stimuli, and emotional reactivity (Burgmer et al., 2011). Gracely et al. (2004) found that subjects high in catastrophising exhibited a positive relationship with bilateral activity in the dorsolateral prefrontal cortex (DLPFC). When examining catastrophising in relation to cognitive paradigms, this same activation in the DLPFC was exhibited in a study by Ellingson et al. (2018) who found that fibromyalgia subjects performed both slower and more inaccurately on incongruent Stroop tasks. Considered collectively, this indicates a devotion of attentional resources to nociceptive input and reduced capacity for cognitive distraction.

As found by Campbell et al. (2012), the occurrence of pain catastrophising prior to experiencing actual pain itself has been seemingly justified at a neural basis as well through patterns of DLPFC activation. Burgmer et al. (2011) found increased activity in both the DLPFC and the periaqueductal gray area (PAG), yet only when the intensity of anticipated pain was announced. Implicated in cognitive functions, the involvement of the DLPFC in amplified attention and anticipation of nociceptive stimuli may serve to maintain difficulties with rumination and magnification. Whilst the PAG initially exhibits increased output upon the introduction of pain, it is unable to sustain activation upon receiving successive stimuli in fibromyalgia patients unlike in healthy controls (Cook et al., 2004). Thus, the descending pain inhibitory system exhibits a form of biological helplessness, mirroring that experienced at a psychosocial level. Collectively increased activity in these regions accounts for persistence within each subscale of catastrophising.

In response to nociceptive stimuli, heightened activation has also been evidenced in centres of the limbic system, implicating amplified emotional reactivity (Burgmer et al., 2011). In a study by Gracely et al. (2004), high catastrophising was correlated with increased activity in the bilateral lentiform nuclei, ipsilateral claustrum, and premotor cortex upon application of a sustained pressure stimulus. The positive correlation of heightened catastrophising with emotional expression is somewhat complicated by the disproportionate representation of genders within the study, with two females taking part for every one male (Gracely et al., 2004). While this does manage to improve upon many clinical studies in which 85-95% of subjects are female, it does somewhat limit overall generalizability (Paschali et al., 2021).

Treatment Approaches to Catastrophising

Background

Presently, there is no generally agreed upon treatment for fibromyalgia, with many doctors recommending a multi-modal approach. Treatment plans typically include a variety of general relaxation routines, pain neurophysiology education (PNE), physical activity, and medications. However, these tactics purport little to no long-term benefits nor are they universally accepted (Alda et al., 2011). A study by Kohns et al. (2020) found that online-based PNE failed to produce any significant effects on catastrophising, distress, life satisfaction, and kinesiophobia.

Researchers speculated that successful short-term reductions in pain intensity were merely due to novel ways of thinking patients had been introduced to, though these gains were lost upon follow-up (Kohns et al., 2020). While the Food and Drug Administration in the United States has currently approved pregabalin, duloxetine, and milnacipran for fibromyalgia treatment, these medications were not extended the same endorsement by European supervisory authorities (Alda et al., 2011). However, despite their limited efficacy and risk of numerous side effects, these medications and analgesics remain amongst the most regularly utilized treatment methods by those who suffer from chronic pain (Pierce et al., 2020). In the absence of satisfactory results, recent studies have begun to examine the prospective value of psychotherapy as an additive strategy for fibromyalgia treatment (Burns et al., 2021). Considering the wide array of psychosocial and physiological factors pain catastrophising has been shown to both mediate and predict, these therapies are poised to bring about change not only in superficial symptoms of fibromyalgia, but also in the deeper underpinnings of the condition.

Cognitive-Behavioural Therapy

The pillar of modern psychotherapy, cognitive-behavioural therapy (CBT) is the most well-studied therapy approach in treating fibromyalgia (Luciano et al., 2014). Using cognitive restructuring and coping mechanisms, patients are taught to rework distorted cognitions they may have and recognize maladaptive reflexive thoughts about their condition (Burns et al., 2021). In a foundational study, Alda et al. (2011) conducted a large-scale experiment comparing CBT to treatment as usual (TAU) to the recommended pharmacological treatment (RPT). CBT proved superior to both TAU and RPT at producing improvements in global function, quality of life, and pain catastrophising across all three subscales of the PCS both post-treatment as well as at a six-month follow-up (Alda et al., 2011). Abnormally elevated in those with high catastrophising, CBT has also been shown to decrease resting state functional connectivity between the primary somatosensory cortex and the insula, providing evidence of neural adaptation (Lazaridou et al., 2017).

Other results of the Alda et al. (2011) study across additional markers were more mixed, with no effective change produced in pain levels nor any significant between group differences in depression scores. A bleaker outlook was cast by a meta-analysis of CBT in fibromyalgia, with no significant effects noted post-treatment nor at a median six-month follow-up on quality of life, pain levels, fatigue, nor sleep quality (Bernardy et al., 2010). When viewed as a composite, CBT produces both irregular and temporary effects in only a small number of common outcome markers such as global function and pain catastrophising (Alda et al., 2011). This ushered in new research into pioneering psychotherapies as applied to fibromyalgia, namely Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Cognitive Therapy (MBCT).

Acceptance and Commitment Therapy

Rather than formulating strategies to control pain directly, ACT preaches therapeutic benefit in acknowledging pain as a part of everyday life (Rickardsson et al., 2021). The instrumental construct as well as treatment goal within ACT is to manipulate stubborn psychological inflexibility, whereby patients learn to experience pain and distress, yet still act in sync with their values (Simister et al., 2018). In a randomized control trial (RCT) by Wicksell et al. (2012), group ACT (GACT) performed for a period of 12 weeks produced significant improvements in psychological inflexibility, functioning, quality of life, global fibromyalgia impact, and affective conditions. These promising results were replicated in a second RCT by Luciano et al. (2014) in which GACT was compared to RPT and wait list (WL) participants. GACT exhibited significant improvements in global functioning, pain acceptance, quality of life, pain catastrophising, pain intensity, anxiety, and depression immediately post-treatment as well as at a six-month follow-up (Luciano et al., 2014). For fibromyalgia patients high in catastrophising, adopting a flexible mindset may allow for a shift in focus away from negative fixations towards a more positive outset as they learn to pursue desired daily activities despite the presence of pain.

A key neural structure of focus in ACT, the bilateral grey matter volume of the bed nucleus of the stria terminalis (BNST) exhibits a positive relationship with psychological inflexibility in fibromyalgia patients (Feliu-Soler et al., 2020). Enlargement of the BNST is associated with increased catastrophising, functional disability, amplified perceived stress, and depressive symptomology (Feliu-Soler et al., 2020). Although decreased BNST volume following MBCT was not seen by Feliu-Soler et al. (2020), future studies are needed to test the same construct against ACT and additional neuroanatomical features such as functional activity and white matter tracts.

Mindfulness-Based Cognitive Therapy

Encompassing many therapeutic permutations, MBCT instructs patients to refrain from assigning a positive or negative valence to thoughts and sensations as they occur (Dorado et al., 2018). Patients are taught to provide them fleeting recognition, assisting with the goal of cultivating awareness in the present moment (Burns et al., 2021). Instrumental in reducing anticipatory anxiety, mindfulness practices are extremely beneficial for populations exhibiting high catastrophising in which cognitive patterns serve to further affective conditions (Vencatachellum et al., 2021). In a RCT by Pérez-Aranda et al. (2019), TAU and PNE were compared against Mindfulness-Based Stress Reduction (MBSR). Researchers found that MBSR was superior to TAU and PNE in producing short-term outcomes for catastrophising, perceived stress, cognitive disabilities, anxiety, and depression (Pérez-Aranda et al., 2019). Often appealing due to its self-guided nature, MBSR is a structured eight-week program including Hatha yoga, meditation, purposeful movement, awareness exercises, and typically audiotapes to reinforce key takeaways (Marikar Bawa et al., 2021). Long-term benefits were retained for catastrophising alone, however psychological flexibility was found to mediate effects of other variables (Pérez-Aranda et al., 2019). This suggests value in combining the treatment principles of ACT with the ease of MBSR.

While the pathogenesis of fibromyalgia remains elusive, the effectiveness of MBCT has proven effective when measured against markers of fibromyalgia outcomes and serum-based biomarkers (Curtis et al., 2011). Compared to subjects who received TAU alone, those who underwent MBSR along with TAU exhibited improvements in psychological inflexibility, pain levels, fatigue, musculoskeletal rigidity, and sleep quality (Andrés-Rodríguez, 2019). Ratios of baseline pro-inflammatory IL-6 and CXCL8 to anti-inflammatory IL-10 were shown to influence psychological flexibility outcomes specifically while levels of CXCL8 were correlated with the efficacy of MBSR itself (Andrés-Rodríguez, 2019). Unlike in the TAU group, MBSR prevented anti-inflammatory IL-10 from decreasing throughout the duration of the 12-month study (Andrés-Rodríguez, 2019). Furthermore, a study by Sanabria-Mazo et al. (2020) found that mindfulness-based training was significantly more effective than relaxation therapy in reducing abnormally elevated levels of brain-derived neurotrophic factor (BDNF) in fibromyalgia patients. When considering the proliferation of faulty neuroplasticity due to excessive BDNF along with the impact of inflammatory cytokines, MBCT interventions have the potential to interrupt the phenomenon of hyperalgesia and physiological cycles perpetuating pain catastrophising (Sanabria-Mazo et al., 2020).

Ethical Considerations

As outlined by the British Psychological Society, all research must closely adhere to the four ethical principles of respect, competence, responsibility, and integrity (BPS, 2009). When working with fibromyalgia patients, concepts of respect, responsibility, and integrity in experimental design must be carefully considered. Due to the low to negligible success of mainstream treatments for fibromyalgia, this population is often left suffering from chronic illness with no promise of resolution (Paschali et al., 2021). Some researchers have even postulated that healthcare-seeking behaviour actually serves to alleviate helplessness within fibromyalgia patients (Ford, 1997). These notions leave patients exceptionally vulnerable to fall prey to therapeutic misconception when contemplating whether to take place in a scientific experiment (Christopher et al., 2017). Recommendations will be made throughout this dialogue to maximize ethical procedures to accommodate unique concerns that may be encountered when working with this population.

Respect

Informed Consent

Paramount in upholding respect of all subjects set to participate in an experiment is obtaining valid informed consent. This ensures that participants are well-informed as to the goals and procedures of the research they are about to undertake (BPS, 2009). While severity often varies in relation to pain intensity, fibromyalgia patients frequently report cognitive issues ranging from mild concentration difficulties to pronounced memory complaints (Sallinen et al., 2018; Castel et al., 2021). A threat to capacity, this necessitates slow delivery and focused repetition of experimental procedures to ensure full comprehension.

Therapeutic Misconception

A significant risk to participants’ autonomy, therapeutic misconception is exhibited when a patient confuses the key differences between receiving standard medical care and participating in experimental research (Shumway et al., 2020). Therapeutic misconception often comes about due to a participant’s false belief that treatment will be individualized to their personal needs, misplaced expectations of personal gain, or failure to understand the objectives of a clinical study (Durand-Zaleski et al., 2008). The first study of its kind, research by Christopher et al. (2017) found that taking part in a scientific reframing intervention prior to completing informed consent significantly lowered the incidence of therapeutic misconception, without sacrificing willingness to participate. This same protocol would be extremely beneficial when working with fibromyalgia patients to ensure they understand the objectives of the research study, randomization protocols, the necessity for any blinding of subjects or researchers that may occur, as well as how taking part may affect their current treatment plan for the duration of the study (Christopher et al., 2017). Subjects should always be advised of the nature of their voluntary participation as well as their right to withdraw from the study at any time, even if consent is given (BPS, 2009). Together, these safeguards should serve to further subjects’ grasp of conducting a valid scientific study, moving the focus away from the concept of personalized treatment for oneself.

Privacy and Confidentiality

Participants should always be assured that data collected throughout a study will be processed and stored anonymously (BPS, 2009). As treatment interventions often require a multi-disciplinary team of individuals, subjects should provide express permission for each person their personal health data is disclosed to. Additionally, increasing numbers of fibromyalgia patients are attracted to the ease of online-based self-guided mindfulness interventions (Dorado et al., 2018). While these programs show promising efficacy, protections must be taken to guarantee that such large quantities of data are anonymised, securely encrypted, and undergo regular backup (Salaffi et al., 2020).

Responsibility

Maximizing Benefits and Minimizing Harm

Researchers have a responsibility to all participants to minimize distress as much as possible throughout the course of the study (BPS, 2009). This is an extremely important concept to consider when working with fibromyalgia patients in which both peripheral and central sensitization mechanisms of dysfunction are implicated (Burgmer et al., 2011). In pressure-evoked pain trials, as compared to healthy controls, fibromyalgia patients required only 63% of an identical stimulus to reach the same subjective pain score (Schreiber et al., 2017). This phenomenon should be accounted for through equalization of pain stimuli across experimental and control groups, utilizing subjective rather than objective intensities as in Lazaridou et al. (2017). Furthermore, painful after sensations are evidenced in fibromyalgia populations, corresponding with unusually prolonged activation noted in the medial temporal lobe following mechanical stimulus (Schreiber et al., 2017). Care should be exercised when taking blood draws, readying subjects for neuroimaging exams, and providing adequate rest time between application of nociceptive stimuli to ensure that subjects have fully recovered from previous inputs.

Integrity

Honesty and Openness

Subjects have a right to be fully informed of any emotional or physical risks taking part in an experiment may pose to them (BPS, 2009). Patients with fibromyalgia are uniquely sensitive to both emotional and physical stress due to dysregulated HPA functioning and blunted diurnal cortisol activity (Curtis et al., 2011). Thus, it is imperative that researchers fully disclose any forms of added demand the experiment may introduce in addition to whatever stress load they are already subject to. Experimental procedures should be presented to participants in a straightforward manner with plenty of time allowed for any questions and clarification. Subjects should be provided with a list of project coordinators and research workers that they are encouraged to contact in the event that any concerns arise prior to commencement of the study.

Unlike the psychotherapies focused on in this review, pharmaceuticals such as pregabalin, duloxetine, and analgesics carry the risk of many potential side effects (Bernardy et al., 2010). The most commonly reported side effects include nausea, dry mouth, drowsiness, constipation, headache, and fatigue (Luciano et al., 2014). Subjects should be made aware of these potential risks if they are assigned to the RPT arm of a clinical trial as well as repeatedly assured that they are free to withdraw from the study without providing reason. If participants decide to withdraw during the course of the study, a list of community resources may be beneficial in mitigating any adverse sentiments that might be experienced upon dropout.

Conclusion

A critical review of existing literature supports the notion of pain catastrophising as a robust risk factor for the development and perpetuation of fibromyalgia. Measured via the PCS across dimensions of rumination, magnification, and helplessness, catastrophising predicates numerous variables of disease outcome including quality of life, pain intensity, disability, and global functioning (Gracely et al., 2004). High levels of catastrophising are further reflected biologically through amplified activation in attentional, anticipatory, and emotional centres of the brain (Ellingson et al., 2018). While CBT literature reports mixed and transitory results, ACT and MBCT studies suggest promising efficacy for addressing not only catastrophising but also a wide range of fibromyalgia complaints (Wicksell et al., 2012; Dorado et al., 2018). Due to the vulnerable emotional and physical state fibromyalgia imposes, researchers should take care to uphold stringent ethics when considering respect, responsibility, and integrity in experimental design (BPS, 2009).

Although this review focused on catastrophising as a primary outcome, the same was not necessarily true of all included studies where it was sometimes a secondary measure. Thus, the parameters of certain studies may have been better suited to study different constructs such as pain intensity. Studies utilizing provoked pain exhibit methodological heterogeneity, inducing both mechanical and thermal nociception. Additionally, it is not uncommon within pain studies for numerous constructs to be measured within the same study. While this provides for a significant amount of information, it is difficult to obtain focused information on one concept such as pain catastrophising alone. Regarding literature on fibromyalgia treatment, research on psychotherapy as applied to fibromyalgia is still relatively new and large-scale studies of high quality are still lacking.

Future research into fibromyalgia should focus heavily on individualized treatment tailored to different stages of disease chronicity as well as increasing the methodological power behind trials. As cognitive focus within catastrophising shifts from rumination to magnification to helplessness as the course of the disease progresses, goals within psychotherapy should be adapted to reflect this (Rodero et al., 2010). Multiple studies to date have confirmed the superior efficacy of CBT, ACT, and MBCT over standard treatment options including pharmacological care (Alda et al., 2011; Wicksell et al., 2012; Pérez-Aranda et al., 2019). However, no crossover trials have been offered to date. This is a much-needed logical progression, not only to uphold a standard of fairness in interactions, but also to further the quest for sustainable treatment options for a trying and burdensome disease to society.

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