Brain Biomarkers for Chronic Pain: Pathway for Novel Therapeutics

A Pathway for Novel Therapeutics

Chronic pain conditions are associated with abnormalities in brain structure and function.

Moreover, some studies indicate that brain activity related to the subjective perception of chronic pain may be distinct from activity for acute pain. However, the latter are based on observations from cross-sectional studies.

In a subset of subacute back pain patients, we followed brain activity for back pain longitudinally over a 1-year period, and compared brain activity between those who recover (recovered acute/sub-acute back pain group) and those in which the back pain persists.

Brain activity for back pain in the early, acute/subacute back pain group is limited to regions involved in acute pain, whereas in the chronic back pain group, activity is confined to emotion-related circuitry. Reward circuitry was equally represented in both groups. In the recovered acute/subacute back pain group, brain activity diminished in time, whereas in the persistent acute/subacute back pain group, activity diminished in acute pain regions, increased in emotion-related circuitry, and remained unchanged in reward circuitry.

Dr. Apkarian’s research integrates brain imaging, psychophysiology, and computational modeling to understand the neural, and biobehavioral mechanisms that underlie chronic pain and chronic pain modulation.

His research focus has been on mechanistic pharmacological randomized controlled trials for both prevention and treatment of chronic muscoloskeletal pain. These include opioid, antidepressant, and dopaminergic pharmacotherapies, with an aim of understanding mechanisms by which these drugs work to relieve pain, as well as for prediction of treatment outcomes.

• Reckziegel D, Vachon-Presseau E, Petre B, Schnitzer TJ, Baliki MN and Apkarian AV. Deconstructing biomarkers for chronic pain: Context and hypothesis dependent biomarker types in relation to chronic pain. PAIN, 2019.
• Apkarian AV and Reckziegel D. Peripheral and central viewpoints of chronic pain, and translational implications. Neuroscience Letters, 2019.
• Cottam WJ, Iwabuchi SJ, Drabek MM, Reckziegel D and Auer DP. Altered connectivity of the right anterior insula drives the pain connectome changes in chronic knee osteoarthritis. PAIN, 2018.
• Reckziegel D, Bailey H, Cottam WJ, Tench CR, Mahajan RP, Walsh DA, Knaggs RD and Auer DP. Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome. BMJ open, 2017.
• Reckziegel D, Raschke F, Cottam WJ and Auer DP. Cingulate GABA levels inversely correlate with the intensity of ongoing chronic knee osteoarthritis pain. Molecular Pain, 2016.
• Cottam WJ, Condon L, Alshuft H, Reckziegel D and Auer DP. Associations of limbic-aective brain activity and severity of ongoing chronic arthritis pain are explained by trait anxiety. NeuroImage: Clinical, 2016.
• Apkarian, A. V., Baliki, M. N., & Geha, P. Y. (2009). Towards a theory of chronic pain. Progress in neurobiology, 87(2), 81-97.
• Hashmi, J. A., Baliki, M. N., Huang, L., Baria, A. T., Torbey, S., Hermann, K. M., … & Apkarian, A. V. (2013). Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain, 136(9), 2751-2768.
• Vachon-Presseau, E., Berger, S. E., Abdullah, T. B., Huang, L., Cecchi, G. A., Griffith, J. W., … & Apkarian, A. V. (2018). Brain and psychological determinants of placebo pill response in chronic pain patients. Nature communications, 9(1), 3397.
• Chang, P. C., Centeno, M. V., Procissi, D., Baria, A., & Apkarian, A. V. (2017). Brain activity for tactile allodynia: a longitudinal awake rat fMRI study tracking emergence of neuropathic pain. Pain, 158(3), 488.
• Davis, D. A., Ghantous, M. E., Farmer, M. A., Baria, A. T., & Apkarian, A. V. (2016). Identifying brain nociceptive information transmission in patients with chronic somatic pain. Pain Reports, 1(4).
• Petre, B., Torbey, S., Griffith, J. W., De Oliveira, G., Herrmann, K., Mansour, A., … & Apkarian, A. V. (2015). Smoking increases risk of pain chronification through shared corticostriatal circuitry. Human brain mapping, 36(2), 683-694.
• Christopher deCharms, R., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., … & Mackey, S. C. (2005). Control over brain activation and pain learned by using real-time functional MRI. Proceedings of the National Academy of Sciences, 102(51), 18626-18631.
• Yarnitsky, D. (2018). Why Does Acute Post Whiplash Injury Pain Transform into Chronic Pain Multi-Modal Assessment of Risk Factors and Predictors of Pain Chronification. Technion Research and Development Foundation Haifa Israel.
• Ochsner, K. N., Knierim, K., Ludlow, D. H., Hanelin, J., Ramachandran, T., Glover, G., & Mackey, S. C. (2004). Reflecting upon feelings: an fMRI study of neural systems supporting the attribution of emotion to self and other. Journal of cognitive neuroscience, 16(10), 1746-1772.
• Neugebauer, V., Galhardo, V., Maione, S., & Mackey, S. C. (2009). Forebrain pain mechanisms. Brain research reviews, 60(1), 226-242.