Descending pain modulation hubs and cortical influences: a narrative review of mechanisms and therapies

Descending pain regulation has been widely studied in animals and recent studies in humans have offered new insights into this complex mechanism. This review paper aims to investigate this process in humans to better understand how pain is modulated in the body. This review included primary articles from PubMed related to pain modulation in the human brain or spinal cord. Book chapters, sources using animal models, and review papers were excluded from the paper. Findings consistently noted the periaqueductal grey and rostral medulla as central hubs of descending pain modulation, while cortical regions including the prefrontal cortex, anterior cingulate cortex, insula, and amygdala exhibited variable and context-dependent contributions. Cognitive and emotional processes, including distraction, imagery, music, catastrophizing, and anxiety, were found to modulate descending pain pathways via altered connectivity between cortical and brainstem regions. Studies also identified therapeutic applications, with transcranial direct current stimulation and spinal cord stimulation demonstrating effects on descending modulatory circuits. These studies identify exciting new progress in our understanding of pain modulation whilst also highlighting a need for further study in human populations to clarify certain inferences.