Behavioral and neural mechanisms underlying odor modulation of pain perception

<p indent="0mm">Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Compared to traditional pharmacological treatments (such as non‑steroidal anti‑inflammatory drugs and opioid analgesics), non‑pharmacological interventions (such as cognitive behavioral therapy, mindfulness meditation, and music therapy) for analgesia generally demonstrate higher safety, lower risks of addiction and side effects, and greater cost‑effectiveness. Among these multisensory, non‑drug approaches, odor‑mediated modulation of pain perception and its clinical translation have attracted growing interest, owing to the close genetic and neural processing links between the olfactory system and the emotional and nociceptive systems. This review systematically synthesizes behavioral and neurobiological evidence on odor-induced modulation of pain and, on this basis, proposes testable models of potential neural pathways, with the aims of informing mechanistic research and providing insights into the clinical translation of odor-based interventions as adjunct strategies for pain management. From the perspective of behavioral research, odor stimulation exhibits distinct dimension-specificity in modulating pain across the sensory-discriminative dimension (pain intensity, pain threshold) and the affective-motivational dimension (pain unpleasantness, pain tolerance). Existing studies suggest that the modulation of odor on the sensory-discriminative dimension of pain shows relatively inconsistent outcomes. Odor-induced emotional changes may not directly regulate an individual’s perception of pain intensity, while attention to odor may reduce perceived pain intensity, though conclusive experimental evidence for this is still lacking. In contrast, current research more consistently demonstrates that odor stimulation modulates the perception of pain unpleasantness. Specifically, individuals tend to report lower pain unpleasantness under pleasant odor conditions, and higher pain unpleasantness under unpleasant odor conditions. Further evidence from neural mechanisms suggests that olfactory stimuli may participate in modulating the ascending transmission and descending inhibitory pathways of pain through two potential neural pathways. One is the emotional and reward neural pathway, where odor stimulation engages emotion-and reward-processing brain regions, such as the amygdala and ventral striatum, to alter the activation of both the ascending medial pain pathway and the descending inhibitory pathway, thereby modulating the unpleasantness of pain. The other is the attentional neural pathway, where odor stimulation acts on the anterior insula and collaborates with the frontoparietal attention network to modify the activation of the ascending lateral pain pathway and the descending inhibitory pathway, thereby regulating the subjective perception of pain intensity. Building on the current evidence, future studies should more precisely dissociate odor-evoked emotional and attentional effects through refined paradigms and more stringent manipulation checks to further validate the dimension-specific nature of odor-induced pain modulation. Moreover, emerging techniques such as cortico-spinal synchronized functional magnetic resonance imaging may enable direct assessment of odor-related modulation at the spinal level, thereby delineating a more comprehensive central pathway underlying odor-induced pain regulation.