Conditioned pain modulation affects the withdrawal reflex pattern to nociceptive stimulation in humans

Human studies have repeatedly shown that conditioning pain modulation (CPM) exerts an overall descending inhibitory effect over spinal nociceptive activity. Previous studies have reported a reduction of the nociceptive withdrawal reflex (NWR) under CPM. Still, how descending control influences the muscle activation patterns involved in this protective behavior remains unknown. This study aimed to characterize the effects of CPM on the withdrawal pattern assessed by a muscle synergy analysis of several muscles involved in the lower limb NWR. To trigger descending inhibition, CPM paradigm was applied using the cold-pressor test (CPT) as conditioning stimulus. Sixteen healthy volunteers participated. The NWR was evoked by electrical stimulation on the arch of the foot before, during and after the CPT. Electromyographic (EMG) activity of two proximal (rectus femoris and biceps femoris) and two distal (tibialis anterior and soleus) muscles was recorded. A muscle synergy analysis was performed on the decomposition of the EMG signals, based on a non-negative matrix factorization algorithm. Results showed that two synergies (Module I and II) were sufficient to describe the NWR pattern. Under CPM, Module I activation amplitude was significantly reduced in a narrow time-window interval (118-156 ms) mainly affecting distal muscles, whereas Module II activation amplitude was significantly reduced in a wider time-window interval (150-250 ms), predominantly affecting proximal muscles. These findings suggest that proximal muscles are largely under supraspinal control. The descending inhibitory drive exerted onto the spinal cord may adjust the withdrawal pattern by differential recruitment of the muscles involved in the protective behavior.