Cortical disinhibition in peripheral neuropathy unveiled by exploratory analysis of spectral alterations in contact heat–evoked potential

ABSTRACT: Neuropathic pain affects 20% to 60% of patients with peripheral neuropathy, generally considered a consequence of nociceptor hypersensitivity. Nevertheless, persistent peripheral nociceptive input may induce central sensitization, a maladaptive neuroplasticity that amplifies neuropathic pain. Contact heat-evoked potential (CHEP) measurement noninvasively assesses the functional integrity of thermonociceptive pathways. Although previous research documented altered CHEP latency and amplitude in neuropathic pain, spectral alterations of CHEP remain underexplored. This exploratory study acquired CHEP data using multichannel electroencephalography (EEG) from 48 patients (29 painful and 19 painless) with peripheral neuropathy and 30 healthy controls. The CHEP power spectrum was analyzed using the "fitting oscillations and one over f" (FOOOF) method to assess the underlying excitation-inhibition balance. We systematically analyzed changes in the spectral exponent and alpha-band oscillations across early (post-I) and late (post-II) poststimulation periods in the frontal, central, and parietal areas. Compared with controls, only painful patients exhibited a significantly attenuated increase in the exponent for the post-Ⅱ vs baseline period in the central and parietal areas, whereas both painful and painless patients exhibited a significant decrease in alpha-band power (alpha-band event-related desynchronization) in both post-I and post-II periods and across all 3 brain areas. These spectral changes may reflect cortical disinhibition in nociceptive responses. Moreover, attenuated increase in the poststimulus exponent in the frontal area was significantly associated with more severe skin nerve degeneration in the lower limbs. Our findings suggest that these spectral alterations may represent an electrophysiological manifestation of central sensitization in peripheral neuropathy, providing novel evidence of brain functional alterations.