Imaging of pain
Acute pain is an adaptive physiological protective system against physical damage or injury. Chronic pain (lasting over 3 months) can be viewed as a disease rather than a symptom, and it affects 20% of the adult population in the EU. The international association for the study of pain (IASP) defines three types of chronic pain: nociceptive pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors; nociplastic pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain; and neuropathic pain that is caused by a lesion or disease of the somatosensory nervous system (Sandström, 2021). Rheumatoid arthritis (RA) is a nociceptive chronic peripheral inflammatory pain disorder. Fibromyalgia (FM) is a nociplastic, chronic widespread pain disorder, characterized by a change in function of nociceptive pathways, leading to generalized hypersensitivity to sensory stimuli.
The pathways and brain regions involved in pain processing are relatively well-characterised, and the neural mechanisms involved in pain processing can be studied using fMRI, PET, MEG, and EEG. Pain-induced activation in the brain can be studied using perfusion PET radiotracers. Neural metabolism can be assessed with [18F]FDG PET. Neurotransmission of pain can be studied using PET radiopharmaceuticals that target noradrenaline, serotonin, opioid, substance P, glutamatergic, GABAergic, and cannabinoid systems. Additionally, dopamine system is involved in modulation of pain (Hagelberg et al., 2004). Pain is often linked to inflammation. Astrocytes and microglia in CNS and peripheral glial cells contribute to nociceptive signalling and pain. Neuroinflammatory mechanisms link pain and depression (Burke et al., 2015). Inflammation in pain has been studied using TSPO radioligands.
TSPO expression in the central nervous system is normally low, but can be upregulated in glial cells (microglia and astrocytes) during neuroinflammation. Regional brain and spinal cord uptake increases of [11C]PBR28 have been observed in patients with chronic low back pain, ALS, and fibromyalgia (Loggia et al., 2015; Albrecht et al. 2018a, 2018b, and 2019). In particular, thalamic SUVR (using whole brain as reference) of [11C]PBR28 is increased in chronic low back pain (Torrado-Carvajal et al., 2021).
Voltage-gated sodium ion channels (VGSCs) play an essential role in pain signalling pathways in sensory neurons in the peripheral nervous system. [18F]fluorolidocaine targets VGSCs, and can be used for imaging neuropathic injury and pain (Bartolo et al., 2022).
Benzon HT, Raja SN, Fishman SM, Liu SS, Cohen SP (eds.): Essentials of Pain Medicine, 4th ed., Elsevier, 2018. doi: 10.1016/C2014-0-03837-3.
Gebhart GF, Schmidt RF (eds.): Encyclopedia of Pain, 2nd ed., Springer, 2013. doi: 10.1007/978-3-642-28753-4.
Shyu B-C, Tominaga M (eds.): Advances in Pain Research: Mechanisms and Modulation of Chronic Pain. Springer, 2018. doi: 10.1007/978-981-13-1756-9.
Tung K-W, Behera D, Biswal S. Neuropathic pain mechanisms and imaging. Semin Musculoskelet Radiol. 2015; 19: 103–111. doi: 10.1055/s-0035-1547371.
Updated at: 2023-01-25
Created at: 2021-04-20
Written by: Vesa Oikonen