Perceptual Correlate of Nociceptive Long-Term Potentiation (LTP) in Humans Shares the Time Course of Early-LTP

Abstract

As in neocortex and hippocampus, neurons in the dorsal horn of the spinal cord develop long-term potentiation of synaptic efficacy (LTP) on high-frequency stimulation (HFS) of their afferent input, although how long LTP lasts in this nociceptive relay nucleus has not yet been addressed. Here we studied neurogenic hyperalgesia, a perceptual correlate of nociceptive LTP, in 13 healthy subjects, after HFS (5 × 1 s at 100 Hz) of superficial cutaneous afferents. HFS led to a mean upward shift of the stimulus–response function for pinprick-evoked pain (punctate mechanical hyperalgesia) in all subjects by a factor of 2.5 ( P < 0.001) that lasted undiminished for the initial 1-h observation period. Follow-up tests until the next day revealed that this type of neurogenic hyperalgesia decayed with a t1/2 of 3.3 h (99% CI: 3.1–3.5 h) and disappeared completely within 25.4 h (99% CI: 20.4–31.6 h). Touch-evoked pain (dynamic mechanical allodynia) developed in eight of 13 subjects, decayed with a t1/2 of 2.9 h from the maximum and disappeared within 9.3 h. These findings suggest that a single HFS session induces nociceptive LTP in healthy subjects that corresponds to early-LTP (LTP1), implying primarily posttranslational mechanisms for this type of plasticity of human pain perception.