Neuroimaging for Chronic Pain: IASP Consensus Statement

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"Patients seek objective testing to demonstrate the reality of an invisible condition that is sometimes subject to doubt."
"Patients seek objective testing to demonstrate the reality of an invisible condition that is sometimes subject to doubt."

With an estimated prevalence of up to 35% among US adults, chronic pain has far-reaching and multifaceted effects.1 In addition to the personal impact on patients' health and quality of life, there are substantial costs to society at large, healthcare systems, and other institutions. As such, health and disability insurance companies seek methods to confirm the pain status of beneficiaries to corroborate self-report, which is the current gold standard for pain assessment in clinical and research settings.

Many practitioners, researchers, and patients also appeal for techniques that could objectively measure pain, albeit for different reasons. "Patients seek objective testing to demonstrate the reality of an invisible condition that is sometimes subject to doubt, researchers seek brain imaging markers that provide scientific, diagnostic and prognostic information that cannot be provided by patient self-reporting, and legal representatives and officials seek techniques to supplement self-reporting and objectively support or challenge claims related to chronic pain," according to a new consensus statement by a task force of the International Association for the Study of Pain (IASP).2

The use of brain imaging tests, including functional magnetic resonance imaging (fMRI), electroencephalography, positron emission tomography (PET), and magnetoencephalography, has been proposed as a means of obtaining objective measures of pain. In the consensus statement published online in September 2017, the IASP task force sought to provide criteria for neuroimaging for chronic pain assessment that would serve as a "pain-o-meter," as well as to discuss related technical, ethical, biological, and legal issues. Particularly relevant to this topic is a 2015 US court case in which the judge ruled that fMRI findings were admissible as evidence of a plaintiff's pain in a personal injury case, although no precedent was established, as the case was settled out of court.3 "There was a need for this statement because of the growing call from legal communities and healthcare insurers, particularly in the US, to be able to validate a claim of chronic pain," says task force chair Karen D. Davis, PhD, a neuroscience professor at the University of Toronto, and head of the Division of Brain, Imaging and Behaviour-Systems Neuroscience at the Krembil Research Institute of Toronto Western Hospital, Ontario, Canada. "The recent use of brain imaging technologies to provide evidence in this way raised concerns amongst some in the scientific community because of the known limitations of applying brain decoding approaches, [which] provide some scientific knowledge about pain in general in groups of patients, to individual patients in pain," she told Clinical Pain Advisor.

The paper clarifies definitions of key terms that are often misused, such as nociception and pain. Nociception is the mechanism by which the central and peripheral nervous systems process information about noxious stimuli, whereas pain is the perception generated when this information reaches the cerebral cortex.4 The concepts are related, although each can occur in the absence of the other. The experience of pain requires consciousness, whereas nociception does not, as demonstrated by results showing signs of nociception in anesthetized patients.5

Brain imaging technologies "measure indices of brain activity that can provide information about nociception and, by inference, pain, but brain imaging data can only be a proxy measure of pain," the authors of the IASP report wrote. "Consequently, any claims about an individual's subjective experience of pain that are based on decoded brain imaging and activity are necessarily inferential (as is the inference of pain on the basis of an individual's behaviour)."

They also distinguish between evoked and ongoing pain and the different imaging approaches required for each type, and they describe the 3 kinds of activity related to chronic pain that may be assessed via functional brain imaging: evoked activity, particularly as it differs between patients and healthy individuals or between affected and unaffected areas of a patient's body and as it correlates with pain intensity; resting-state brain activity as an indication of the functional connectivity related to processes involved in chronic pain and as a way of distinguishing these from healthy controls; and activity linked to a specific attribute of chronic pain via PET or arterial spin labelling measurements of cerebral blood flow.

However, specific brain networks or areas exclusively associated with chronic pain have yet to be identified, and several of the processes linked to chronic pain have also been observed in other conditions such as depression and anxiety.6,7 In addition to this lack of specificity and the issue of "reverse inference," the statement also points to individual variability as 1 of the challenges of leveraging neuroimaging for pain. Although common patterns have been observed in the brains of patients with chronic pain, brain activity related to pain responses varies not only between patients but also within each patient as a function of time.8,9

The task force outlines the following 7 criteria for the evaluation of neuromarkers of pain:

  1. Measures to be used as pain neuromarkers must be precisely defined.
  2. The neuromarker must have demonstrated applicability to individuals.
  3. Methodological procedures used during testing for a neuromarker must be validated.
  4. Neuromarkers must have established internal consistency, as well as positive and negative controls to enable validation for each individual tested.
  5. The neuromarker must be diagnostic for pain, with established sensitivity, specificity, and positive and negative predictive value for pain at the individual level.
  6. The neuromarker must be validated with converging methods, such as invasive animal or human studies.
  7. The neuromarker must be generalizable to the patient group tested and to the test conditions.

Also covered in the statement are neuroethical issues pertaining to the use of neuroimaging in litigation that require further exploration, including access to such techniques based on financial status, the discrediting of subjective experience, and privacy and protection of patient data.

As available modalities do not yet meet the criteria specified by the task force, the authors state that their use for legal purposes would be unethical and inappropriate at present. "The representation of pain in the brain is complex, different for different individuals, and overlaps with other systems (salience and attention, for example), and so, a specific marker of chronic pain does not exist," says Dr Davis. "In essence, what the courts are really looking for is a lie detector test and not a pain detector test."

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References

  1. Johannes CB, Le TK, Zhou X, Johnston JA, Dworkin RH. The prevalence of chronic pain in United States adults: results of an Internet-based survey. J Pain. 2010; 11(11):1230-1239.
  2. Davis KD, Flor H, Greely HT, et al. Brain imaging tests for chronic pain: medical, legal and ethical issues and recommendations. Nat Rev Neurol. 2017;13(10):624-638.
  3. Davis K. Personal injury lawyers turn to neuroscience to back claims of chronic pain. ABA J. 2016.
  4. National Research Council Committee on Recognition and Alleviation of Pain in Laboratory Animals. Recognition and alleviation of pain in laboratory animals; chapter 2 – mechanisms of pain. Washington, DC: National Academies Press; 2009.
  5. Ní Mhuircheartaigh R, Warnaby C, Rogers R, Jbabdi S, Tracey I. Slow-wave activity saturation and thalamocortical isolation during propofol anesthesia in humans. Sci Transl Med. 2013;5(208):208ra148.
  6. Bushnell MC, Ceko M, Low LA. Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci. 2013;14(7):502-511.
  7. Borsook D, Edwards R, Elman I, Becerra L, Levine J. Pain and analgesia: the value of salience circuits. Prog Neurobiol. 2013;104:93-105.
  8. Davis KD, Moayedi M. Central mechanisms of pain revealed through functional and structural MRI. J Neuroimmune Pharmacol. 2013; 8(3):518-534.
  9. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463-484.
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