We have recently established a model of LTP- and LTD-like bidirectional plasticity of human pain perception (Klein et al., J. Neurosci. 24 (2004) 964-971). Now we investigated the impact of variations in spatial and temporal conditioning parameters on the magnitude and direction of plasticity.

The skin of the thigh was stimulated through a multipolar electrode array (diameter 30 mm, 48 pin electrodes) with 500 or 1000 pulses at 1, 10 and 100 Hz in 12 healthy human volunteers (intensity: 10x detection threshold). LTP magnitude grew linearly with the frequency of conditioning stimulation (significantly different between frequencies, at least p<0.05). Longer pulse trains (1000 pulses) tended to give stronger LTP (p=0.07). Unexpectedly, LTD-like responses were never seen.

Testing at the conditioned and at an adjacent (unconditioned) test site revealed similar and highly correlated responses (r=0.91) suggesting heterosynaptic facilitation as the dominant underlying process. The direction and magnitude of the response depended significantly on the number of electrodes and size of the stimulated skin area. Namely, stimulation through a small 10 pin electrode resulted in significant LTD, while stimulation through the large 48 pin electrode resulted in significant LTP.

We conclude that heterosynaptic frequency-dependent LTP plays a substantial role in nociceptive plasticity and overrides homo- synaptic LTD (Supp. by DFG Tr236/16-2 & BMBF 01EM0506).