The intrinsic reason why complementary tests (clinical neurophysiology, neuroimaging, skin biopsy) cannot establish the diagnosis of neuropathic pain

Neuropathic pain is defined as pain caused by a lesion or disease of the somatosensory nervous system. Current algorithms for neuropathic pain diagnosis include patient history, clinical examination, and complementary tests to confirm a lesion or disease of the somatosensory nervous system, able to change the diagnosis of neuropathic pain from probable to definite. These tests include clinical neurophysiology, such as pain-related evoked potentials, quantitative sensory testing, skin biopsy to measure intraepidermal nerve fiber density, or magnetic resonance imaging. However, these tests are especially relevant to demonstrate a structural lesion of the somatosensory system leading to sensory deficit, but they cannot establish a causal link between nervous lesion and the presence of pain. Similar lesions of the somatosensory nervous system may be accompanied by pain or not, while neuropathic pain can be a matter of sensitization or hyperexcitability of somatosensory structures without overt structural lesion. Even the existence of hyperexcitability of nociceptive pathways, revealed by neurophysiological or genetic tests, may contribute to the emergence of pain, but may not be sufficient to affirm that this results in ongoing neuropathic pain. Thus, various complementary tests can be useful to identify a lesion of the somatosensory nervous system, but not to confirm the presence of associated neuropathic pain. Clinical assessment, considering disease history, symptom descriptors and a plausible neuroanatomical distribution, remains the cornerstone of the diagnosis of neuropathic pain, while paraclinical findings must be interpreted with caution in this regard.