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crps-like pain is associated with bone bruises or articular surface trauma. these entities, however, are not clearly associated with immune activation and they frequently regress [ 42 ]. rather, tissue damage associated with pain appears to require the participation of the innate immune system [ 22 ]. indeed, the occurrence of articular surface lesions or bone bruises and their subsequent response to non-steroidal anti-inflammatory drugs, which are used as first-line pain therapies for crps patients, are associated with the infiltration of leukocytes, particularly macrophages, into the affected tissues [ 5, 42, 43, 44 ]. crps-like pain induced by these insults is also sensitive to inflammatory antagonists, such as oral cyclooxygenase inhibitors, intravenous ketorolac, and etanercept. these data suggest that enhanced neuropeptide-mediated mast cell activation, keratinocyte chemotaxis, and cytokine production might contribute to the activation of the innate immune system in post-traumatic pain. furthermore, these events may be a unifying pathophysiology in different types of injury-induced pain, including but not limited to crps, complex regional pain syndrome, and fibromyalgia. however, recent evidence has shown that the adaptive immune system could play a role in the initiation of the pain cascade in crps as well as a potential marker of disease severity [ 6, 46, 49, 50 ].

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it is then reasonable to assume that proms that are mostly used in clinical trials reflect the situation of the average patient at the time of the trial. therefore, including proms as standard items in future clinical trials can improve the information available for surgeons for the treatment of complex fractures. we aim to build a user-friendly easily accessible platform that enables the clinician to include patients' opinions.