The Brain
The first prominent theory of pain, proposed by Descartes, stated that pain was an injury or pathology-determined sensory process; however, it is now accepted that pain perception is a complex, biopsychosocial process that involves sensory, cognitive, and emotional processing. In 1965, Melzack and Wall proposed the Gate Control Theory of Pain, which revolutionized pain science. The Gate Control Theory of Pain emphasized the active role of central, neural mechanisms in pain perception and modulation.14 Specifically, the Gate Control Theory proposed that a gating mechanism in the dorsal horn of the spine modulates nerve impulses from afferent fibers to spinal cord transmission cells, and small and large fibers can open and close the “Gate,” respectively. Descending nerve impulses from the brain also act on the gating mechanism. Collectively, the Gate affects the output of spinal cord transmission cells in response to stimulation, and the level of central and sensory inputs affects brain activity. Ultimately, the experience of “pain” occurs when brain activity reaches a certain level.
The Gate Control Theory and the subsequent efforts to expand on this work highlighted the importance of central input modulation and biopsychosocial mechanisms in pain processing. With greater use of the spinal cordotomy procedure, phantom limb pain challenges led Melzack to expand on the Gate Control Theory and propose the neuromatrix concept. The development of the neuromatrix stemmed from the understanding that central neural processes and sensory perception can be modulated and experienced with or without peripheral inputs. The neuromatrix model postulates that the interaction of cognitive, sensory, and affective neural components determines pain perception and pain modulatory responses.15 Thus, the brain interprets cognitive, sensory, and affective inputs to determine whether stimulation is dangerous (i.e., painful), how painful that stimulation is, and what descending modulatory or protective response is needed.
Advances in brain imaging methodologies have allowed for the identification of neural components implicated in pain processing and examination of chronic pain-related alterations in neural processes. Imaging data consistently indicate that brain areas associated with sensory, cognitive, emotional, social, and behavioral processes make up what is now often referred to as the pain connectome.'6 Specifically, key brain regions responsible for nociceptive and pain processing include the primary and secondary somatosensory cortices, primary motor and supplementary motor cortices, insular cortex, anterior cingulate cortex, prefrontal cortex, thalamus, and regions in the hippocampus, amygdala, and basal ganglia that process fear, emotion, and memory.1718 Although similar brain regions are implicated in chronic pain processing, extant data suggest that individuals with chronic pain exhibit dysfunction in endogenous pain modulatory systems, structural (i.e. grey matter density and volume) and functional (i.e., default mode network and regional connectivity) brain differences, and alterations in neurochemical systems (i.e., glutamatergic, GABAergic, opioidergic, and dopaminergic systems).17-19
Further, findings from imaging and experimental pain studies indicate that individuals with chronic pain may exhibit central sensitization. Central sensitization is a process by which the brain experiences pain in response to an innocuous stimulus and amplifies and/or prolongs this perception of pain. This amplified pain response may occur from both increased activation of nociceptive pathways and dysfunction in descending pain modulatory systems.
Given the evidence of neural dysfunction or alteration in regions or neurochemical processes associated with cognitive, and emotional functioning, it is not surprising that individuals with chronic pain exhibit impairment in these areas. Individuals with chronic pain demonstrate impairment in working memory tasks, emotional decision-making, awareness, and judgment.2021 More recent work highlights how the associated psychobiological stress associated with the progression of chronic pain may result in altered reward-aversion homeostatic function.22 As chronic pain progresses, allostatic load increases, and surges in stress-related neurochemicals (e.g., norepinephrine, glutamate, vasopressin) result in reward deficiency and negative affective states, such as decreased motivation, anxiety, and depression.
Cognitive-behavioral and neuromodulatory (e.g., hypnosis and mindfulness) psychological treatment may help reduce the negative impact of chronic pain. Imaging studies show that these therapies have an effect on pain-related brain structure and function. Mindfulness meditation has been shown to increase activity in the anterior cingulate cortex and insula and induce analgesia through non-opioidergic mechanisms.23-24 Imaging studies examining hypnosis report hypnotic analgesia activity in pain-processing supraspinal areas, including the thalamus, sensory cortices, insula, anterior cingulate cortex, and frontal attentional control systems.25-27 Data also suggest that cognitive-behavioral-based therapies may affect cognitive control, or top-down processing of pain. Specifically, participation in cognitive-behavioral therapy has been shown to increase prefrontal cortex activation (ventrolateral prefrontal/lateral orbitofrontal cortex), increase gray matter in the posterior parietal and prefrontal cortices, and decrease the processing of painful input in somatosensory and midcingulate cortices.17-28-30
Taken together, neuroimaging data provide important insights into the role of cognitive and emotional processing of pain and support a biopsychosocial approach to understanding and addressing chronic pain. Psychological factors affect how pain is experienced, and chronic pain is associated with altered neurological functioning and impaired functioning. Thus, the chronic pain state is likely to result in an unfortunate negative cycle if integrative treatment is not provided.
