Repeated exposure to cutaneous high-frequency electrical stimulation prolongs the time course of secondary hyperalgesia

J Neurophysiol. 2025 May 12. doi: 10.1152/jn.00130.2025. Online ahead of print.

ABSTRACT

Exposure to noxious stimuli induces secondary hyperalgesia (SH), likely due to long-term potentiation (LTP) in the dorsal horn or ‘central sensitization’. Previous studies have suggested that repeated exposure to a sensitizing stimulus may promote persistent form of potentiation. We tested this hypothesis by characterizing time course and spatial spread of SH induced by repeated exposures to high-frequency electrical stimulation (HFS) in healthy volunteers. Separate groups of 16 participants received either a single session of 5 or 10 HFS trains (‘HFS 1×5’ and ‘HFS 1×10’ groups), or two sessions of 5 HFS trains separated by one hour and applied to the same forearm (‘HFS 2×5’ group) or the contralateral forearm (‘HFS 2×5 bilateral’ group). HFS trains consisted in 1-second 100 Hz stimulation (20x detection threshold). The magnitude and spread of SH were assessed using pinprick stimulation at 9 time-points up to 24 hours post-HFS. Temporal decay of HFS-induced increase in pinprick sensitivity was significantly slower in the ‘HFS 2×5’ versus the ‘HFS 1×5’ and ‘HFS 1×10’ groups (half-life: 438 vs 255 vs 247 min). In contrast, the time course of hyperalgesia area was similar in the ‘HFS 2×5’ and ‘HFS 1×5’ groups (451 and 470 min) but decayed more rapidly in the ‘HFS 1×10’ group (92 min). In the ‘HFS 2×5 bilateral’ group, pre-exposure to HFS on one forearm did not affect contralateral hyperalgesia magnitude or half-life, but slightly increased its spatial extent. These findings suggest that repeated exposure to noxious stimulation favors induction of a longer-lasting form of central sensitization.

PMID:40354167 | DOI:10.1152/jn.00130.2025