The article reviews the brain mechanisms involved in pain perception and regulation, both in health and disease. It highlights the role of supraspinal brain regions in processing acute and chronic pain, emphasizing the contributions of various imaging techniques. The authors conducted a systematic review of studies using hemodynamic (PET, fMRI), neuroelectrical (EEG, MEG), and neurochemical methods (MRS, receptor binding, neurotransmitter modulation) to examine brain activity during pain. The meta-analysis of 68 hemodynamic studies and 30 neuroelectrical studies revealed that multiple brain regions, including the primary and secondary somatosensory cortices (S1, S2), insular cortex (IC), anterior cingulate cortex (ACC), prefrontal cortex (PFC), and thalamus (Th), are activated during acute pain. These regions are involved in somatotopic organization, psychological modulation, and the temporal sequence of cortical activity. The study also found that the brain network for acute pain perception in normal subjects differs from that in chronic clinical pain conditions, with chronic pain engaging regions critical for cognitive and emotional assessments. Neurochemical studies highlighted the role of opioid and catecholamine transmitters and receptors in pain modulation, influenced by environmental and genetic factors. The review concludes that the nociceptive system is a complex sensory system, and pain experience is strongly modulated by interactions between ascending and descending pathways. Understanding these mechanisms is crucial for developing effective treatments for chronic pain conditions.The article reviews the brain mechanisms involved in pain perception and regulation, both in health and disease. It highlights the role of supraspinal brain regions in processing acute and chronic pain, emphasizing the contributions of various imaging techniques. The authors conducted a systematic review of studies using hemodynamic (PET, fMRI), neuroelectrical (EEG, MEG), and neurochemical methods (MRS, receptor binding, neurotransmitter modulation) to examine brain activity during pain. The meta-analysis of 68 hemodynamic studies and 30 neuroelectrical studies revealed that multiple brain regions, including the primary and secondary somatosensory cortices (S1, S2), insular cortex (IC), anterior cingulate cortex (ACC), prefrontal cortex (PFC), and thalamus (Th), are activated during acute pain. These regions are involved in somatotopic organization, psychological modulation, and the temporal sequence of cortical activity. The study also found that the brain network for acute pain perception in normal subjects differs from that in chronic clinical pain conditions, with chronic pain engaging regions critical for cognitive and emotional assessments. Neurochemical studies highlighted the role of opioid and catecholamine transmitters and receptors in pain modulation, influenced by environmental and genetic factors. The review concludes that the nociceptive system is a complex sensory system, and pain experience is strongly modulated by interactions between ascending and descending pathways. Understanding these mechanisms is crucial for developing effective treatments for chronic pain conditions.