Nociplastic pain: towards an understanding of prevalent pain conditions

Nociplastic pain represents a third mechanistically distinct category of chronic pain, separate from nociceptive pain (caused by tissue damage) and neuropathic pain (caused by nerve injury). This comprehensive review addresses the need for a new clinical framework to describe pain conditions where symptoms are disproportionate to identifiable tissue or nerve damage, accompanied by central nervous system symptoms such as fatigue, sleep disturbance, cognitive problems, and mood disorders. These conditions have historically been stigmatized with terms like "medically unexplained syndromes," creating diagnostic and therapeutic challenges for both patients and healthcare providers.

The paper systematically reviews the neurophysiological mechanisms underlying nociplastic pain, including amplified central sensory processing, altered pain modulation at spinal and supraspinal levels, and evidence from functional brain imaging showing differential neural activation. The authors present diagnostic criteria and clinical characteristics for major nociplastic pain syndromes including fibromyalgia, chronic widespread pain, complex regional pain syndrome, temporomandibular disorder, irritable bowel syndrome, bladder pain syndrome, and chronic primary musculoskeletal pain. They emphasize that nociplastic pain frequently exists on a continuum with nociceptive and neuropathic pain, with many chronic pain conditions exhibiting mixed-pain characteristics.

Key findings highlight that nociplastic pain affects 5-15% of the general population with higher prevalence in women, and diagnosis is typically delayed (averaging 35 months and 4.5 physician consultations for fibromyalgia). The review demonstrates that these conditions respond poorly to peripherally-directed therapies such as anti-inflammatory drugs, opioids, and surgery, but may benefit from centrally-acting medications and non-pharmacological interventions. Imaging studies reveal changes in brain regions involved in pain processing and reduced activity in descending analgesic pathways.

Clinically, the paper provides practical guidance emphasizing that diagnosis should be based on characteristic symptom patterns rather than biomarkers, without requiring unnecessary investigations that may promote medicalization. Management should prioritize non-pharmacological approaches including patient education, cognitive-behavioral therapy, physical activity, and psychological interventions, with pharmacotherapy reserved for supplementary benefit. The authors advocate for a biopsychosocial approach and interdisciplinary care when available, shifting the paradigm from seeking peripheral pathology to understanding the neurobiological mechanisms of central sensitization, thereby legitimizing patient symptoms and enabling mechanism-based treatment strategies.