Site- and modality-specific modulation of experimental muscle pain in humans

The neurophysiological mechanisms involved in diffuse noxious inhibitory controls (DNIC) have been investigated extensively, but information is lacking about the effect of different stimulus modalities and somatic locations on the effectiveness of DNIC. This study is the first to examine the hypoalgesic effects on a deep, tonic and painful test stimulus (TS) of both painful and non-painful conditioning stimuli (CS) applied to different sites of the body. Two separate experiments were performed using painful electrical stimulation of the left anterior tibialis muscle as the TS. In the first experiment (n = 9), injection of 5% hypertonic saline was used as a painful CS into one of four muscles: anterior tibialis of each leg and brachioradialis of each arm. In the second experiment (n = 5), a non-painful vibratory stimulus was used as the CS at the same four sites. Compared with TS alone, the perceived pain intensity of the TS increased (4.5 +/- 1.8%; P = 0.019) in combination with the painful CS applied to the same muscle (ipsilateral homotopic site), but decreased (-25.3 +/- 1.4%; P < 0.001) in combination with non-painful CS at the same site. Both painful and non-painful CS applied at the three heterotopic sites caused significant and site-dependent decreases in the perceived pain intensity of the TS (range 15%-37%; P < 0.05). We conclude that a hypoalgesic DNIC-like effect on muscle pain is not produced exclusively by painful stimuli, and that the valence and magnitude of the modulation depend on the nature of the CS and its location relative to the applied TS.