by Diana Payne, Ph.D., QME
What is Pain?In 1994, the International Association for the Study of Pain proposed the following definition of pain: “Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.” Interestingly, this definition, still commonly used today, seemed to foreshadow several recent findings in the field, namely that there is an inherent emotional component to pain, and that pain may not involve actual tissue damage. As we will see, with the benefit of significant advances in brain imaging technology, the recent literature on chronic pain and associated brain changes clearly demonstrates these points.
What is Chronic Pain? There is no agreed-upon definition of chronic pain, but it is broadly defined as pain persisting at least three to six months past the inciting event, and extending past the healing process from the initial injury. Other definitions focus upon the disconnect between the original tissue damage and ongoing pain, saying that chronic pain is when the degree and quality of the pain are uncoupled from bodily injury and persist for more than six months. Still others focus not just on the unpleasant physical sensation, but also on the myriad on associated cognitive, behavioral, and emotional comorbidities. But whatever the definition, all agree that chronic pain profoundly threatens a person’s well-being and quality of life.
The Brain and Plasticity. One of the most significant breakthroughs in the field of neuroscience was the discovery that the brain is adaptive, or plastic, and can and does change under normal healthy conditions. For example, early on, it was found that musicians show increased gray matter and cortical thickness in areas associated with auditory processing. One early longitudinal study involved training in a specialized task (juggling) and showed structural brain changes in areas involved in processing complex visual motion in as few as seven days of training. This body of research unequivocally shows that ongoing experience produces structural changes in the brain. Given the salience of chronic pain in the sufferer’s life, it is then not surprising that this experience also produces structural brain changes.
Pain Representation in the Brain. There is no one “pain center” in the brain; that is, there is no one fixed or critical brain region for pain, and no one area is exclusively activated during pain experiences. Rather, functional imaging studies show that pain is the product of a widely distributed neural network in the brain, where each component of this network serves a multitude of functions, not just pain processing. There is no one necessary or sufficient brain region for pain, and no known pattern of brain activity absolutely indicative of pain (e.g., for medical or legal purposes). But there is one region, the posterior insula, that is consistently activated during pain (from nociceptive stimuli) and this may represent a critical neural node for pain processing. (See Apkarian, Hashmi, & Baliki, 2011; Lee & Tracey, 2013.). Pain typically arises from activation of nociceptors (peripheral sensory receptors that can detect actual or threatened damage to tissue). But, interestingly, parts of this network can be accessed by non-nociceptive events or inputs to produce pain-like experiences. For example, studies have shown that the experience of emotional pain, such as romantic rejection or social exclusion, activate pain centers much like that of physical pain (Eisenberger, Lieberman & Williams, 2003; Kross, et al., 2011).
Structural Brain Changes with Chronic Pain. Structural brain imaging studies have shown that there are distinct brain changes associated with chronic pain. At least ten different chronic pain syndromes have demonstrated brain morphometry changes, including: chronic back pain (CBP), phantom pain, fibromyalgia, irritable bowel syndrome, and complex regional pain syndrome (CRPS). Interestingly even somatoform pain disorders show structural brain changes, including gray matter loss in pain-processing structures. One study demonstrated 1.3 cm3 loss of gray matter for every year of CBP. (See Newman et al., 2014 for a review.)
There are also functional brain alterations, some even indicating that chronic pain harms cortical areas unrelated to pain. For example, one study found that chronic pain significantly disturbs the brains “default-mode network” (consisting of areas active during the brain’s resting state), suggesting that chronic pain actually has a widespread impact on overall brain function (Baliki et al., 2008).
UCLA doctor Emeran Mayer, whose research focuses on chronic pain and biological changes in the brain, was recently quoted in a news release as saying, “So I think a lot of people now agree with the concept that chronic pain is a brain disease. It may start anywhere in the body when you have acute pain, but once it becomes a chronic pain syndrome it does become a brain disease.”
One surprising finding in the research is that each of the different chronic pain conditions studied has a distinct impact on brain function and architecture. The changes in brain morphology have a distinct signature, depending on the pain condition. For example, CBP and fibromyalgia are associated with gray matter reduction in the whole brain, whereas in CRPS they are closer to controls. As another example, there is some indication that CBP is more associated with changes to the medial prefrontal cortex compared to other chronic pain conditions. (See Newman, et al., 2014.)
But, independent of the exact nature of these changes, it appears that across chronic pain patients there is a decrease in gray matter, often in the cingulate cortex, insula, and dorsolateral prefrontal cortex. Functionally, chronic pain conditions seem to preferentially engage medial prefrontal cortical areas, subcortical limbic regions, especially portions of the dorsal and ventral basal ganglia, amygdala, and hippocampus. Given the known functioning in these cortical and subcortical regions, it appears that with chronic pain, there is a shift away from brain regions for sensory processing of pain toward regions for encoding emotional and motivational subjective states. In other words, once pain transitions to chronic (> 3 months), the representation of pain shifts away from sensory regions and gradually engages the emotion and reward circuitry. One prominent researcher (Apkarian, 2004) concludes that chronic pain is more emotional in nature than acute pain.
Timing of Brain Changes. In one study, brain changes were seen following only 8 days of exposure to repetitive experimental noxious stimuli (van Hecke, Torrance, & Smith, 2013). But the time required to reach a stable representation in the brain is more likely several months. Also, the timing likely differs amongst pain conditions, and amongst the different brain structures themselves; but certainly within the first year. It is noteworthy that this time period closely matches the clinical definition for the chronic pain (3-12 months). It appears that within the first year, this state is “carved” into the brain, which then remains relatively constant.
Fortunately, while these changes are a serious concern, it does appear that at least some of the brain changes do reverse when pain is substantially relieved. And this finding is particularly important because it supports the argument that these structural changes are a consequence of chronic pain, rather than the cause of the chronic pain. One study found that the dorsolateral prefrontal cortex thickened in response to improvement in pain, and that the extent of thickening correlated with the extent of clinical improvement (Lee & Tracey, 2013). Another study examined primary hip osteoarthritis, the only chronic pain condition that can be considered curable (following total hip replacement), and found that the main differences in brain structure receded when the pain was cured (Rodriguez-Raecke et al., 2009). In the induced noxious stimuli study (van Hecke et al., 2013), the brain changes receded between 22 days and 12 months.
Predictors of Transition to Chronicity. One important question in this literature is what initiates this transition into chronicity. Some have argued for the critical importance of psychosocial risk factors in accounting for this transition, including catastrophizing, pain related fear of injury or reinjury, depression, occupational or legal status, and so on. Others have argued that emotion-driven learning events (e.g., pain is uncontrollable) initiate a cascade of events that ultimately reorganize the brain into a chronic pain state. There is some support for this idea that psychological factors are involved. For example, one study of low back pain found the extent of reorganization in the somatosensory cortex (expanded representation for the low back) was related to duration and intensity of pain; however, comorbid depression and anxiety were associated with larger effects. This suggests the shift was driven in part by characteristics of the pain itself, but by also by the emotional impact of the pain as well (Wand, et al., 2011). But one longitudinal study (Hashmi et al., 2013) found that the shift in brain activity in the transition to chronic pain was in fact independent of levels of depression and anxiety. This suggests that the salient properties of the pain itself were sufficient to induce the shift from acute pain circuitry to emotion circuitry.
Apkarian (2010) concluded there is sufficient evidence that the mood disorders so commonly associated with chronic pain actually, to some extent, reflect a consequence of the reorganized brain reward circuitry. Thus, it may well be that emotional states precipitate the transition to chronicity, but then the structural brain changes associated with pain chronicity then themselves drive emotional conditions. Further, it may be that these structural and emotional changes then contribute to the maintenance of the chronic pain state, in a self-perpetuating system.
What are the Implications of these Findings? As Apkarian (2010) points out, standard methods for treating chronic pain have been dismally unsuccessful, and it may be because these focus on approaches aimed at acute pain systems. It is also clear that emotions are critically and “inextricably intertwined” in the development and maintenance of chronic pain. It may well be that treatment aimed at modifying and manipulating processes underlying the emotional suffering (cortical-limbic circuitry) will ultimately be the key in successful treatment of chronic pain. At the very least, pain management requires a multidisciplinary approach, with the incorporation of mental health.
Dr. Diana Payne has nearly 20 years of combined experience conducting psychological evaluations in research, pharmaceutical, and forensic settings. She divides her time between UCLA, where she is a Project Director, and conducting forensic evaluations, including Workers' Compensation, Civil Litigation, and Short and Long Term Disability. She has authored or co-authored research articles published in journals such as Archives of General Psychiatry, Behavior Genetics, Journal of Research in Personality, and Journal of Clinical Psychopharmacology.
Apkarian, A.V. (2010). Human brain imaging studies of chronic pain. In Kruger L. & Light, A.R. (editors) Translational Pain Research: From Mouse to Man. Boca Raton, FL: CRC Press.
Apkarian, A.V., Hashmi, J.A., & Baliki, M.N. (2011). Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain. Pain; 152: S49-S64.
Baliki,M.N., Geha, P.Y., Apkarian, A.V., & Chialvo, D.R. (2008). Beyond feeling: Chronic pain hurts the brain, disrupting the default-mode network dynamics. The Journal of Neuroscience; 28: 1398-1403.
Eisenberger, N., Lieberman, M.D., & Williams, K.D. (2003). Does rejection hurt? An fMRI study of social exclusion. Science; 302: 290-292.
Hashmi, J.A., Baliki, M.N., Huang, L., Baria, A.T., Torbey, S., Hermann, K.M., Schnitzer, T.J., & Apkarian, A.V. (2013). Shape shifting pain: Chronification of back pain shifts brain representation from nociceptive to emotion circuits. Brain; 136: 2751-2768.
Kross, E., Berman, M.G., Mischel, W., Smith, E.E., & Wager, T.D. (2011). Social rejection shares somatosensory representations with physical pain. PNAS; 108: 6270-6275.
Lee, M.C. & Tracey, I. (2013). Imaging pain: A potent means for investigating pain mechanisms in patients. British Journal of Anaesthesia; 111: 64-72.
Newman, E., Moulton, E., Becerra, L., & Borsook, D. (2014). Morphological brain changes in chronic pain: Mystery and meaning. In C.Y. Saab (editor) Chronic Pain and Brain Abnormalities. London: Elsevier.
Rodriguez-Raecke, R., Niemeier, A., Ihle, K., Ruether, W., & May, A. (2009). Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. The Journal of Neuroscience; 29: 13746-13750.
Van Hecke, O., Torrance, N., & Smith, B.H. (2013). Chronic pain epidemiology – where do lifestyle factors fit in? The British Pain Society; 7: 209-217.
Wand, B.M., Parkitny, L., O’Connell, N.E., Luomajoki, H., McAuley, J.H., Thacker, M., & Moseley, G.L. (2011). Cortical changes in chronic low back pain: Current state of the art and implications for clinical practice. Manual Therapy; 16: 15-20.