Modulation of Conditioned Pain by C-Tactile Afferent Stimulation: Spinal, Cortical, and Behavioral Evidence

C-tactile (CT) afferents are a specialized subclass of unmyelinated C-fibers that respond optimally to slow, caress-like touch and are found predominantly in hairy skin (McGlone et al., 2014). These fibers project from the dorsal horn to thalamic and posterior insula regions, where their firing strongly correlates with subjective pleasantness (Ackerley et al., 2014). Beyond mediating affective aspects of touch, CT-fiber activation has been shown to reduce pain (Liljencrantz et al., 2014; Reddan et al., 2020) and to modulate somatosensory processing at cortical levels (Ribeiro-Carreira et al., 2025). Cortical regions such as the insula and anterior cingulate cortex (ACC), which integrate somatosensory, nociceptive, and social-emotional inputs, are consistently activated during CT-optimal touch (Gordon et al., 2013; Morrison, 2016), highlighting their potential role in these modulatory effects. However, the mechanisms through which CT stimulation interacts with nociceptive pathways—whether through spinal inhibition, supraspinal modulation, or engagement of socio-emotional networks—remainS incompletely understood. A key framework for studying descending pain modulation is Conditioned Pain Modulation (CPM), defined as the inhibition of a painful test stimulus by a spatially distinct conditioning noxious stimulus (Youssef et al., 2016). The magnitude of CPM analgesia scales with the intensity of the conditioning stimulus: stronger heterotopic pain leads to stronger inhibition of the test stimulus. Because both heterotopic pain and affective (CT-optimal) touch can modulate nociceptive processing, CT stimulation applied near the test site may interact with CPM by altering the processing of incoming somatosensory and nociceptive signals during descending inhibition. The present experiment investigates this interaction by delivering SEPs concomitant with either CT-optimal brushing, or vibration (discriminative touch) applied on the left forearm while participants immerse their right hand in cold water (conditioning stimulus) to induce CPM. This study should allow us to test whether CT-optimal touch attenuates, enhances, or otherwise shapes CPM-related analgesia when applied concurrently with the conditioning stimulation (cold water). In addition to psychophysiological measurements (Electroencephalography, EEG; Electroespinography, ESG; Electrocardiography ECG), we will assess pressure pain thresholds (PPTs) before and after each condition as a behavioral index of analgesia. Notably, spinal SEP components such as N13 have been shown to be sensitive to CPM, exhibiting amplitude reductions when a heterotopic noxious stimulus is applied during SEP acquisition (Di Pietro et al., 2021). Combining PPTs with spinal and cortical SEP measures therefore enables a comprehensive assessment of how CT-optimal touch modulates CPM across multiple hierarchical levels—from spinal processing to higher-order sensory-affective integration and behavioral measures. Together, this multimodal approach will clarify whether CT-optimal touch strengthens, disrupts, or reshapes descending pain inhibitory pathways during CPM, providing new insights into the interplay between affective touch and endogenous pain modulation systems.