Nociceptive and non-nociceptive rheumatological pain: recent developments in the understanding of pathophysiology and management in rheumatoid arthritis and fibromyalgia

Musculoskeletal disorders, in which pain is the most prevalent and disabling symptom, constitute the commonest cause of disability in the community. Major progress has recently been made in the elucidation of rheumatic pain processing. Based on this information, we construct a classification of rheumatic pain: nociceptive and non-nociceptive. In the former, pain perception is proportional to inflammation or damage, usually in joint structures. In the latter, peripheral noxious stimulation is minimal or unidentifiable, at least at presentation. A prototype disorder of nociceptive pain is rheumatoid arthritis. Pain genesis in this condition entails both peripheral and central sensitization, and neurogenic inflammation. Antinociceptive mechanisms are activated. A prototype disorder of non-nociceptive pain is fibromyalgia. Despite the absence of obvious peripheral nociceptive stimulation, features in keeping with central sensitization have similarly been documented of late, while antinociceptive mechanisms seem defective. There is compelling evidence that neuroendocrine axes disturbances, particularly hypothalamic-pituitary-adrenal axis hypofunction, may mediate the onset and persistence of both nociceptive and non-nociceptive rheumatic pain. Our classification implies the need for a mechanism-based approach. We substantiate this paradigm by evaluating mechanisms of action of promising therapeutic interventions in rheumatic pain.