A novel protocol to investigate the monoaminergic relationship between descending nociceptive and motor unit neuromodulation.

Chronic pain is a multifaceted condition involving complex interactions between sensory and motor systems, in part modulated by monoaminergic neurotransmitters such as serotonin (5-HT) and norepinephrine (NE). Diffuse noxious inhibitory control (DNIC) and motor unit (MU) facilitation are critical processes that reflect descending nociceptive inhibition [1] and motor neuromodulation, respectively. This study presents a novel protocol combining pain-related evoked potentials (PREP) recorded via electroencephalography (EEG) and high-density surface electromyography (HDsEMG) to assess the effects of an experimental painful stimulus-the cold pressor test (CPT)-on both nociceptive and MU neuromodulation. Healthy, young participants completed pre-and post-CPT assessments, with PREP and HDsEMG data collected in three experimental components. Although the sample size was small, promising trends in post-CPT responses for both nociceptive and MU parameters suggest the feasibility of this approach. The findings support the hypothesis that the CPT induces enhanced nociceptive inhibition and MU facilitation in healthy controls, likely mediated by increased widespread monoaminergic drive. Future studies with larger sample sizes and diverse participant populations, including those with chronic pain conditions, will be necessary to validate these results and explore the protocol's ability to capture both nociceptive inhibition and facilitation.Clinical Relevance-This provides the first step towards furthering our understanding of the interplay between nociceptive processing and motor impairments, two of the hallmark signs across chronic pain conditions.