Nociceptive, Neuropathic and Nociplastic Pain in Clinical Practice: Mechanism-Oriented Assessment and Multimodal Management - Systematic Review

Background: Chronic pain is common and increasingly considered a disease - anatomical labels often fail to reflect sustaining mechanisms. The IASP/ICD-11 framework classifies pain as nociceptive, neuropathic, and nociplastic, which often coexist. Aim: To synthesize mechanisms of nociceptive, neuropathic, nociplastic, and mixed pain, and outline a mechanism-oriented, multimodal management approach. Methods: Narrative review of major guidelines, systematic reviews, and pivotal clinical trials. Results: Nociceptive pain reflects ongoing peripheral nociceptor activation and peripheral sensitization; management targets the tissue source and inflammation. Neuropathic pain follows a lesion or disease of the somatosensory system with ectopic firing, neuroinflammation, and central sensitization; first-line drugs include tricyclic antidepressants, SNRIs, and gabapentinoids, while NSAIDs show little benefit in pure neuropathic states. Nociplastic pain involves altered nociceptive processing without clear tissue damage or nerve lesion and is linked to central sensitization, widespread hypersensitivity, fatigue, and sleep/cognitive symptoms; education, graded exercise, and cognitive-behavioral strategies are foundational. Mixed states are common, and sustained peripheral input may promote “centralization,” requiring individualized combinations of therapies. In selected, well-phenotyped neuropathic syndromes, interventional options (e.g., blocks, steroid injections, pulsed radiofrequency, botulinum toxin A, neuromodulation) can be useful adjuncts to rehabilitation and optimized medication. Conclusion: Mechanism-based assessment supports rational, individualized therapy selection. Effective care is multimodal, addressing peripheral generators, neural hyperexcitability, central sensitization, and psychosocial factors, with realistic goals emphasizing function and quality of life.