Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine

Abstract

Chronic pain is a leading cause of disability globally and associated with enormous health-care costs. The discrepancy between the extent of tissue damage and the magnitude of pain, disability, and associated symptoms represents a diagnostic challenge for rheumatology specialists. Central sensitisation, defined as an amplification of neural signalling within the CNS that elicits pain hypersensitivity, has been investigated as a reason for this discrepancy. Features of central sensitisation have been documented in various pain conditions common in rheumatology practice, including fibromyalgia, osteoarthritis, rheumatoid arthritis, Ehlers-Danlos syndrome, upper extremity tendinopathies, headache, and spinal pain. Within individual pain conditions, there is substantial variation among patients in terms of presence and magnitude of central sensitisation, stressing the importance of individual assessment. Central sensitisation predicts poor treatment outcomes in multiple patient populations. The available evidence supports various pharmacological and non-pharmacological strategies to reduce central sensitisation and to improve patient outcomes in several conditions commonly seen in rheumatology practice. These data open up new treatment perspectives, with the possibility for precision pain medicine treatment according to pain phenotyping as a logical next step. With this view, studies suggest the possibility of matching non-pharmacological approaches, or medications, or both to the central sensitisation pain phenotypes.

Nociplastic Pain Criteria or Recognition of Central Sensitization? Pain Phenotyping in the Past, Present and Future

“…The IASP clinical criteria and grading system for nociplastic pain affecting the musculoskeletal system [ 44 ] provide the first set of clinical criteria (1) endorsed by a worldwide scientific organization (i.e., the IASP), and (2) linked to nociplastic pain as the third mechanistic pain descriptor in addition to nociceptive and neuropathic pain. CS is a key underlying mechanism of nociplastic pain [ 44 ], yet CS goes beyond the nociceptive system [ 17 ]. Within this view, it is considered unfortunate that the IASP chose the term nociplastic pain and defined it with a focus on the nociceptive system.…”

“…Precision medicine refers to the ability to classify patients into subgroups that differ in their susceptibility to, biology, or prognosis of a particular disease, or in their response to a specific treatment, and thus to tailor treatment to the individual patient characteristics [ 70 ]. Recent studies suggest that assessment of CS may be used to improve precision pain medicine for rheumatology practices (reviewed in [ 17 ]). This implies that patient education, management and treatments are adapted to the pain phenotype.…”

“…Together, these central nervous system dysfunctions not only contribute to increased responsiveness to a variety of sensory inputs such as tactile stimuli but can also lead to hypersensitivity to non-musculoskeletal stimuli, such as chemical substances, light, sound, heat, cold, stress and electricity [ 16 ]. The knowledge regarding CS has revealed a paradigm shift in the understanding and management of chronic pain that allows clinicians to think beyond muscles and joints and to account for the role of pain modulation in the central nervous system [ 17 ].…”

“…In a variety of chronic musculoskeletal pain conditions, CS has been found to be present in an important subgroup of patients (reviewed in [ 17 ]). These conditions include chronic traumatic neck pain (i.e., whiplash) [ 18 ], fibromyalgia [ 19 ], osteoarthritis [ 20 ], migraine [ 21 ], irritable bowel syndrome [ 22 ], chronic fatigue syndrome [ 23 ], paediatric pain [ 24 ], low back pain [ 25 ], non-traumatic neck pain [ 26 ], rheumatoid arthritis [ 27 ] and pain following cancer [ 6 ].…”

“… Central nervous system sensitization Refers to ‘central sensitization.’ Chronic pain Pain of at least 3 months duration. Endogenous analgesia The body’s ability to activate pain relief, with poor endogenous analgesia considered a feature of central sensitization [ 17 ]. Neuropathic pain Pain due to a lesion or a disease of the nervous system.…”