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A possible biomarker of low back pain: 18F-FDeoxyGlucose uptake in PETscan and CT of the spinal cord

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Published/Copyright: April 1, 2017
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Scandinavian Journal of Pain
From the journal Scandinavian Journal of Pain Volume 15 Issue 1

In this issue of the Scandinavian Journal of Pain, Zhou and coworkers publish an interesting study demonstrating that patients with low back pain (LBP) appear to have increased metabolic activity in the lower thoracic and upper lumbar segments of their spinal cord, compared with patients of same age and sex who do not have LBP [1].

The findings by Zhou et al. implicate that patients with LBP can be differentiated from people without LBP, using PET/CT scan. The uptake of 18F-FDG as PET ligand has a potential as a biological marker of increased metabolic rate in that area.

The increased metabolic rate detected in the affected areas of the spinal cord may represent a process of excitation in the dorsal horn neurons, and/or a visualisation of a neuro-inflammatory process affecting this part of the spinal cord. Both these processes have been claimed to be important for the development of chronic pain. These claims are likely to be true, but there have been very little direct evidence that these phenomena actually take place in patients. The observations made by Zhou et al. are interesting in this respect.

The results represent an objective diagnostic finding in the clinical evaluation of patients suffering from LBP. The findings may have a potential for guidance to better diagnosis, and help for development of better treatments, in order to improve the situation for chronic pain patients.

1 Importance of objective biomarkers for chronic pain

Years lived with disability (YLDs) is a measure of non-fatal health outcome, and pain conditions caused 21% of all YLDs globally [2]. Low back pain, the pain diagnosis explored in this study by Zhou et al., was the leading single cause for YLD followed by depression, anaemia, and neck pain. Thus, low back pain obviously represents a wide spread disease in the world’s population.

Some years ago, in an assessment of different treatments against low back pain, that were offered by “school medicine” and private health care providers, 48 different treatments were listed as being in current use, varying from multimodal pain rehabilitation, analgesic medication, fusion surgery, trigger point blocks, to psychotherapy, hot baths or herbal medicine. All of them were claimed to give relief by the caregivers using the methods, even if the scientific support usually were slight or absent [3]. Even if the knowledge have increase a bit during the last 15 years, this obviously indicates that we have a lack of understanding about the underlying processes actually causing the pain in the low back.

Almost all medical specialties have a foundation in analysis of biomarkers for diagnosis of diseases, and as a guide for treatment choice and treatment effects. In contrast, in the field of pain medicine, there are up to now few or no biomarkers to rely upon. In the pain field, the golden standard of pain assessment is based upon the patients self-report and clinical investigations, but objective, measurable findings are usually absent.

Of course we must trust the patients report, but I often wish that we had better tools to understand the nature of pain related processes, and their pathophysiology. Perhaps biomarker studies in body fluids, e.g. in blood [4], CSF, saliva, or micro-dialysate from painful tissue, or, as in this study by Zhou et al., image biomarkers [5,6] can help us to a better understanding of what actually is going on in the pain patients from a pathophysiological point of view? Could some aspects of these complex processes involved be objectively measured using biomarkers?

2 What is a biomarker?

One frequently used definition says: “… a biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [7]. So far, we have no established validated biomarker to use in pain patients, but the candidate biomarkers presented so far, give some hope for the future.

3 Strong sides of this study

I think that Zhou et al. has used a very clever approach in this study. They have “re-used” data from more than three thousand 18F-FDG PET/CT scans, done in patients because of cancer diagnostics, and from them, by retrospective use of health questionnaires, identified a group of 13 patients suffering from low back pain, and 13 as matched pain free controls. This is a good way to extract information from data that is “already there”, to produce fruitful results stimulating to deeper studies. There is also an economical aspect-the 26 PET/CT scans carried out here would cost around 26 000 US $. In this study this cost was already paid.

4 Limitations of this study

This retrospective, “re-use-design” also introduces some limitations of the present study. The pain problem that these patents suffered from is not described well, but only as: “do you have low back pain – yes or no”. This is certainly not detailed enough, but may anyway provide some useful information. The study was originally not designed as a study of low back pain. The number of subjects included in the study is small, and of course it needs to be repeated in a larger cohort with a better design.

5 Conclusions and implications

Nevertheless, the study Zhou et al., indicate that research on spinal cord image biomarker in pain patients, using PET/CT methodology, may contribute to a better understanding of the biological aspects of the complex pathophysiology of pain. Their investigation demonstrates that pain related processes in the spinal cord may be objectively visualized and quantified with PET/CT imaging. It represents a good early attempt in the search for Identification of an image biomarker in defined clinical pain conditions. The findings may have substantial potential on guidance for better diagnosis, and help for development of better treatments in order to improve the situation for chronic pain patients.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2016.11.017.

Center for Pain Management and Research, Uppsala University Hospital, 75185 Uppsala, Sweden. Fax: +46 18503539.

References

[1] Zhou X, Ciprian P, Kim B, Dhatt H, Rosenberg J, Mittra E, Dob B, Graves E, Biswal S. Detection of nociceptive-related metabolic activity in the spinal cord of low back pain patients using 18F-FDG PET/CT. Scand J Pain 2017;15:53–7.Search in Google Scholar

[2] Hoy D, March L, Brooks P, Blyth F, Woolf A, Bain C, Williams G, Smith E, Vos T, Barendregt J, Murray C, Burstein R, Buchbinder R. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 2014;73:968–74.Search in Google Scholar

[3] SBU. Back and neck pain. Stockholm: Swedish Council on Health Technology Assessment in Health Care (SBU); 2000. SBU report no 145/1 (in Swedish).Search in Google Scholar

[4] Moen A, Lind AL, Thulin M, Kamali-Moghaddam M, Røe C, Gjerstad J, Gordh T. Inflammatory serum protein profiling of patients with lumbar radicular pain one year after disc herniation. Int J Inflam 2016:3874964, http://dx.doi.org/10.1155/2016/3874964.Search in Google Scholar

[5] Linnman C, Appel L, Fredrikson M, Gordh T, Söderlund A, Långström B, Engler H. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation. PLoS One 2011;6:e19182.Search in Google Scholar

[6] Peterson M1, Svärdsudd K, Appel L, Engler H, Aarnio M, Gordh T, Långström B, Sörensen J. PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow: visualizing neurogenic inflammation? PLoS One 2013;8:e75859.Search in Google Scholar

[7] Biomarkers Definitions Working Group. Biomarkers and surrogate end-points: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89–95.Search in Google Scholar
Published Online: 2017-04-01
Published in Print: 2017-04-01

© 2017 Scandinavian Association for the Study of Pain

Articles in the same Issue

  2. Scandinavian Journal of Pain
  3. Editorial comment
  4. Cardiovascular risk reduction as a population strategy for preventing pain?
  5. Observational study
  6. Diabetes mellitus and hyperlipidaemia as risk factors for frequent pain in the back, neck and/or shoulders/arms among adults in Stockholm 2006 to 2010 – Results from the Stockholm Public Health Cohort
  7. Editorial comment
  8. Exercising non-painful muscles can induce hypoalgesia in individuals with chronic pain
  9. Clinical pain research
  10. Exercise induced hypoalgesia is elicited by isometric, but not aerobic exercise in individuals with chronic whiplash associated disorders
  11. Editorial comment
  12. Education of nurses and medical doctors is a sine qua non for improving pain management of hospitalized patients, but not enough
  13. Observational study
  14. Acute pain in the emergency department: Effect of an educational intervention
  15. Editorial comment
  16. Home training in sensorimotor discrimination reduces pain in complex regional pain syndrome (CRPS)
  17. Original experimental
  18. Pain reduction due to novel sensory-motor training in Complex Regional Pain Syndrome I – A pilot study
  19. Editorial comment
  20. How can pain management be improved in hospitalized patients?
  21. Original experimental
  22. Pain and pain management in hospitalized patients before and after an intervention
  23. Editorial comment
  24. Is musculoskeletal pain associated with work engagement?
  25. Clinical pain research
  26. Relationship of musculoskeletal pain and well-being at work – Does pain matter?
  27. Editorial comment
  28. Preoperative quantitative sensory testing (QST) predicting postoperative pain: Image or mirage?
  29. Systematic review
  30. Are preoperative experimental pain assessments correlated with clinical pain outcomes after surgery? A systematic review
  31. Editorial comment
  32. A possible biomarker of low back pain: 18F-FDeoxyGlucose uptake in PETscan and CT of the spinal cord
  33. Observational study
  34. Detection of nociceptive-related metabolic activity in the spinal cord of low back pain patients using 18F-FDG PET/CT
  35. Editorial comment
  36. Patients’ subjective acute pain rating scales (VAS, NRS) are fine; more elaborate evaluations needed for chronic pain, especially in the elderly and demented patients
  37. Clinical pain research
  38. How do medical students use and understand pain rating scales?
  39. Editorial comment
  40. Opioids and the gut; not only constipation and laxatives
  41. Observational study
  42. Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: A nationwide register-based cohort study in Denmark
  43. Editorial comment
  44. Relief of phantom limb pain using mirror therapy: A bit more optimism from retrospective analysis of two studies
  45. Clinical pain research
  46. Trajectory of phantom limb pain relief using mirror therapy: Retrospective analysis of two studies
  47. Editorial comment
  48. Qualitative pain research emphasizes that patients need true information and physicians and nurses need more knowledge of complex regional pain syndrome (CRPS)
  49. Clinical pain research
  50. Adolescents’ experience of complex persistent pain
  51. Editorial comment
  52. New knowledge reduces risk of damage to spinal cord from spinal haematoma after epidural- or spinal-analgesia and from spinal cord stimulator leads
  53. Review
  54. Neuraxial blocks and spinal haematoma: Review of 166 case reports published 1994–2015. Part 1: Demographics and risk-factors
  55. Review
  56. Neuraxial blocks and spinal haematoma: Review of 166 cases published 1994 – 2015. Part 2: diagnosis, treatment, and outcome
  57. Editorial comment
  58. CNS–mechanisms contribute to chronification of pain
  59. Topical review
  60. A neurobiologist’s attempt to understand persistent pain
  61. Editorial Comment
  62. The triumvirate of co-morbid chronic pain, depression, and cognitive impairment: Attacking this “chicken-and-egg” in novel ways
  63. Observational study
  64. Pain and major depressive disorder: Associations with cognitive impairment as measured by the THINC-integrated tool (THINC-it)
https://doi.org/10.1016/j.sjpain.2017.01.004

Articles in the same Issue

  2. Scandinavian Journal of Pain
  3. Editorial comment
  4. Cardiovascular risk reduction as a population strategy for preventing pain?
  5. Observational study
  6. Diabetes mellitus and hyperlipidaemia as risk factors for frequent pain in the back, neck and/or shoulders/arms among adults in Stockholm 2006 to 2010 – Results from the Stockholm Public Health Cohort
  7. Editorial comment
  8. Exercising non-painful muscles can induce hypoalgesia in individuals with chronic pain
  9. Clinical pain research
  10. Exercise induced hypoalgesia is elicited by isometric, but not aerobic exercise in individuals with chronic whiplash associated disorders
  11. Editorial comment
  12. Education of nurses and medical doctors is a sine qua non for improving pain management of hospitalized patients, but not enough
  13. Observational study
  14. Acute pain in the emergency department: Effect of an educational intervention
  15. Editorial comment
  16. Home training in sensorimotor discrimination reduces pain in complex regional pain syndrome (CRPS)
  17. Original experimental
  18. Pain reduction due to novel sensory-motor training in Complex Regional Pain Syndrome I – A pilot study
  19. Editorial comment
  20. How can pain management be improved in hospitalized patients?
  21. Original experimental
  22. Pain and pain management in hospitalized patients before and after an intervention
  23. Editorial comment
  24. Is musculoskeletal pain associated with work engagement?
  25. Clinical pain research
  26. Relationship of musculoskeletal pain and well-being at work – Does pain matter?
  27. Editorial comment
  28. Preoperative quantitative sensory testing (QST) predicting postoperative pain: Image or mirage?
  29. Systematic review
  30. Are preoperative experimental pain assessments correlated with clinical pain outcomes after surgery? A systematic review
  31. Editorial comment
  32. A possible biomarker of low back pain: 18F-FDeoxyGlucose uptake in PETscan and CT of the spinal cord
  33. Observational study
  34. Detection of nociceptive-related metabolic activity in the spinal cord of low back pain patients using 18F-FDG PET/CT
  35. Editorial comment
  36. Patients’ subjective acute pain rating scales (VAS, NRS) are fine; more elaborate evaluations needed for chronic pain, especially in the elderly and demented patients
  37. Clinical pain research
  38. How do medical students use and understand pain rating scales?
  39. Editorial comment
  40. Opioids and the gut; not only constipation and laxatives
  41. Observational study
  42. Healthcare resource use and costs of opioid-induced constipation among non-cancer and cancer patients on opioid therapy: A nationwide register-based cohort study in Denmark
  43. Editorial comment
  44. Relief of phantom limb pain using mirror therapy: A bit more optimism from retrospective analysis of two studies
  45. Clinical pain research
  46. Trajectory of phantom limb pain relief using mirror therapy: Retrospective analysis of two studies
  47. Editorial comment
  48. Qualitative pain research emphasizes that patients need true information and physicians and nurses need more knowledge of complex regional pain syndrome (CRPS)
  49. Clinical pain research
  50. Adolescents’ experience of complex persistent pain
  51. Editorial comment
  52. New knowledge reduces risk of damage to spinal cord from spinal haematoma after epidural- or spinal-analgesia and from spinal cord stimulator leads
  53. Review
  54. Neuraxial blocks and spinal haematoma: Review of 166 case reports published 1994–2015. Part 1: Demographics and risk-factors
  55. Review
  56. Neuraxial blocks and spinal haematoma: Review of 166 cases published 1994 – 2015. Part 2: diagnosis, treatment, and outcome
  57. Editorial comment
  58. CNS–mechanisms contribute to chronification of pain
  59. Topical review
  60. A neurobiologist’s attempt to understand persistent pain
  61. Editorial Comment
  62. The triumvirate of co-morbid chronic pain, depression, and cognitive impairment: Attacking this “chicken-and-egg” in novel ways
  63. Observational study
  64. Pain and major depressive disorder: Associations with cognitive impairment as measured by the THINC-integrated tool (THINC-it)
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