Pain Mechanisms and Pharmacological Pain Relieving Interventions in Rheumatic Diseases

Effective management of pain is one of the greatest challenges among medical interventions. Pathological pain arises most frequently in the musculoskeletal system. The first obligatory step is the localisation of the source and to identify the dominant mechanism, as mechanical, infectious, auto-inflammatory or central. Most musculoskeletal pain by type are nociceptive, however also neuropathic components may be present in acute and chronic painful conditions. Immediate and consequent pain relief in acute pain is essential to prevent the development of chronic pain and pain behaviour. The first alerts for an infectious or auto-inflammatory danger are the alarmins, molecules induced by pathogens or tissue destruction in the cells of the innate host defense. They are activated via their receptors expressed and the signaling cascades producing and secreting their bioactive mediators and pro-inflammatory cytokines. These molecules bind to the respective receptors on the peripheral terminal of the nociceptive neuron and elicit neurotransmitter and action potential response as pain signal for the central nervous system. These repeated signals sensitize the peripheral terminal and the central junctions, causing an increased and persistent pain sensation even in higher nuclei and cortical areas. Most frequent conditions causing mechanical locomotor pains are vertebral joint dystorsions, discogen radicular compressions, osteoporotic vertebral fractures, hip and knee osteoarthritis. Neuropathic mechanisms are dominant in the complex regional pain syndrome as hip algodystrophy or the shoulder-hand syndrome. Inflammatory pain mechanisms, including cytokine effects operate in septic arthritis, rheumatoid and psoriatic arthritis, idiopathic juvenile arthritides, spondyloarthritides, and in acute and chronic gout. The most effective pharmacological tools of pain management are the classical and innovative molecules with special reference to bioproteins and synthetic molecules targeting the key points on the pain pathway. Considerations of recent recommendations may promote the right therapeutic decisions in the care of rheumatic patients suffering from musculoskeletal pain.