Stefan Elbers

11 General introduction Estimates suggest that some 30.3% ( SD = 11.7) of the global population suffers from chronic pain (Elzahaf et al., 2012). Although the duration and intensity vary from person to person, international surveys indicate that the negative effect on wellbeing is considerable. In a European survey including over 5000 people with chronic pain, the median Numeric Rating Scale (NRS) of pain intensity was 7 (range = 5 – 10), and 78% of the sufferers reported a pain duration of at least 2 years (Breivik et al., 2006). The global impact of chronic pain is most evident in the estimates of the WHO burden of disease study where three musculoskeletal pain conditions were among the top 10 biggest contributors of years lived with disability (YLD). Low back pain leads the rankings and accounts for more YLD worldwide than conditions such as diabetes, major depression, and COPD (Blyth et al., 2019; Vos et al., 2017). These statistics indicate that on any given day millions of individuals worldwide have to deal with chronic pain, often for years on end. Unsurprisingly, many of these report comorbidities such as depression, anxiety, fatigue, and an inability to fulfil their social roles (Breivik et al., 2006; Pitcher et al., 2019), leading to a complex cluster of interacting problems that affect social, mental and physical functioning (Doleys, 2017). DEFINITION AND FUNCTION OF PAIN The International Association for the Study of Pain (IASP) defines pain as “ an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage ” (2021). When pain is persisting or recurring for at least three months – which is generally beyond the required time for tissue to heal – it is referred to as chronic pain (Treede et al., 2019). Despite its unpleasantness, the ability to feel pain is an adaptive trait that is crucial for survival (Williams, 2016). This becomes clear when noxious stimuli threaten the body’s integrity. Nearby nociceptors detect the incoming danger and, when sufficiently stimulated, activate peripheral nerve fibers that transmit the signal to higher-order brain regions. Given that the signal is strong enough to capture the attention of these regions and that the situation is evaluated as sufficiently threatening, a pain experience emerges (Brodal, 2017). This experience interrupts ongoing cognitive processes, such as attentional performance, and motivates the individual to deal with the threat (Moore et al., 2019; Vlaeyen & Crombez, 2020). In these situations, pain serves as a symptom - a warning of a potential threat against the body’s integrity. The importance of this mechanism for survival is best illustrated in conditions that are characterized by congenital nociceptor deficiency, such as hereditary sensory and autonomic neuropathy type V, which prevents people experiencing pain after injury (Weisman et al., 2019). This condition leads to many accidental, unrecognized, and untreated self-inflicted wounds, fractures, and cuts, as well as premature death (Erdil et al., 2012; Yozu et al., 2016).