Mechanisms underlying chronic pain differ from those underlying acute pain. In chronic pain states, central nervous system (CNS) factors appear to play particularly prominent roles. In the absence of anatomical causes of persistent pain, medical sub-specialities have historically applied wide-ranging labels (e.g., fibromyalgia (FM), irritable bowel syndrome, interstitial cystitis and somatisation) for what now is emerging as a single common set of CNS processes. The hallmark of these ‘centrally driven’ pain conditions is a diffuse hyperalgesic state identifiable using experimental sensory testing, and corroborated by functional neuroimaging. The characteristic symptoms of these central pain conditions include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of co-morbid mood disorders. In contrast to acute and peripheral pain states that are responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, central pain conditions respond best to CNS neuromodulating agents, such as serotonin–norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants.
The beginning of central pain
Recent findings suggest that subsets of individuals with heretofore-considered ‘peripheral’ or nociceptive pain states, such as knee osteoarthritis (KOA) and chronic low back pain (CLBP), may have prominent central nervous system (CNS) contributions to their pain. The evidence for this includes both mechanistic studies (i.e., experimental pain testing, functional neuroimaging and genetic studies) and therapeutic trials. Thus, ‘any’ chronic pain condition may be a ‘mixed pain state’ with variability at the level of the individual, regarding the degree to which peripheral versus central factors are playing a role. This has tremendous implications for the treatment of chronic pain because subsets of individuals with any rheumatologic disorder may have components of central pain, and the pharmacological and non-pharmacological approaches for treating this type of pain are quite different from those that are effective for treating ‘peripheral’ pain due to damage or inflammation.
While there are clear descriptions of individuals with what we now call fibromyalgia (FM) going back centuries in the medical literature, Sir William Gowers coined the term ‘fibrositis’, which was considered a form of muscular rheumatism caused by inflammation of fibrous tissue overlying muscles. Although other terms such as ‘psychogenic rheumatism’ were proposed and used in the mid-20th century, the term fibrositis remained the most widely used term to describe individuals with chronic widespread pain and no alternative explanation.
Many investigators now believe that chronic pain is itself a disease, and the location of the body where it arises may not be as relevant as an individual’s genetically determined pain sensitivity, combined with neuroplastic changes that can occur in the CNS that lead to augmented pain transmission. These heightened states of pain sensitivity can be associated with hyperalgesia (increased pain in response to normally painful stimuli) and or allodynia (pain in response to normally non-painful stimuli). These states can be triggered by an initial peripheral injury or inflammatory process and may be regional or widespread. The concomitant influence of separate outside stressors (i.e., infection or trauma) may also play a role in the chronicity of the disease .
Several authors began to suggest that FM was a misnomer because there was not inflammation of the muscles. Moldofsky et al. performed seminal studies showing that individuals with fibrositis suffered from objective sleep disturbances, and further showed that these same symptoms could be induced in healthy individuals deprived of sleep . Hudson et al. were arguably the first investigators to note the strong familial tendency to develop FM, and proposed that this condition is a variant of depression, coining the term ‘affective spectrum disorder’ . In parallel during this same period of time, Yunus et al. similarly began to note the high frequency of associated ‘functional somatic syndromes’, such as irritable bowel syndrome (IBS) and headache, with FM, again steering the focus away from skeletal muscle . Nonetheless, the theories positing a pathophysiologic role of skeletal muscle took time to fade, persisting into the mid-1990s .
Just as spastic colitis became IBS, temporomandibular joint syndrome became temporomandibular disorder (when it was recognised that the problem was not in the joint), chronic Epstein–Barr virus (EBV) syndrome became chronic fatigue syndrome (CFS) (when it was realised that this syndrome occurs commonly after many viral illnesses and without infection with only this pathogen), and fibrositis became FM.
FM appears to be more than simply what many clinicians identify as fibromyalgia (FM). There is now significant evidence that FM is part of a much larger continuum that has been given many names, including functional somatic syndromes, medically unexplained symptoms, chronic multisymptom illnesses, somatoform disorders and perhaps most appropriately, central pain or central sensitivity syndromes (CSS). Yunus showed FM to be associated with tension-type headache, migraine and IBS . Together with primary dysmenorrhoea, these entities were depicted by Yunus in a Venn diagram in 1984, emphasising the epidemiological and clinical overlap between the syndromes. In this article, the more recent term ‘central sensitivity syndromes (CSS)’ as proposed by Yunus is used because we feel that this represents the best nosological term at present for these syndromes .
CSS disorders can overlap with a variety of psychiatric disorders. This overlap likely occurs at least in part because the same neurotransmitters (albeit in different brain regions) are operative in psychiatric conditions. The presence of co-morbid psychiatric disturbances is somewhat more common in individuals with CSS seen in tertiary care settings than primary care settings . Fig. 1 demonstrates the overlap between FM, CFS and a variety of regional pain syndromes as well as psychiatric disorders – and shows that the common underlying pathophysiological mechanism seen in most individuals with FM, and in large subsets of individuals with these other syndromes, is CNS pain or sensory amplification.
