Heterotopic and homotopic nociceptive conditioning stimulation: distinct effects of pain modulation

Within an area, habituation and sensitization represent well-established modulatory effects to repetitive noxious input. Less is known regarding the nociceptive conditioning effects between body sites - i.e., how stimulating one site may affect another. Therefore, we investigated the effects of nociceptive stimulation of anatomically distinct locations (shoulder and hand) on pain rating and evoked potentials (i.e., contact heat-evoked potentials).

The effect of stimulation order was assessed in eight healthy subjects. The shoulder was examined before the hand or the hand before the shoulder. All subjects underwent both conditions (shoulder before hand and hand before shoulder) on separate days. In an additional 30 subjects (total n = 38), between retesting the shoulder or the hand, conditioning stimulation in the respective other location (i.e., hand or shoulder) was applied. Both analyses focused upon changes in the magnitude of evoked pain responses in relation to the respective area being conditioned by heterotopic stimulation.

When the shoulder was stimulated before the hand, N2P2 amplitude was significantly reduced. In contrast, stimulating the hand before the shoulder resulted in significant response increments (shorter N2 latency). Additionally, conditioning stimulation of the hand resulted in increased pain rating to shoulder stimulation.

Overall, these findings indicate that response modulation to noxious contact heat stimulation depends upon conditioning stimulus location. These effects represent changes beyond conventional habituation due to repeated stimulation in the same area.