Home Medicine The triumvirate of co-morbid chronic pain, depression, and cognitive impairment: Attacking this “chicken-and-egg” in novel ways
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The triumvirate of co-morbid chronic pain, depression, and cognitive impairment: Attacking this “chicken-and-egg” in novel ways

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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, Daniella Cha et al. have looked at the overlapping problems of depression, chronic pain and cognitive impairment in a unique way [1]. As they state, these three entities are well-known to be comorbid. As they also state, there has been an interest in looking at the three problems as a single entity, thus defining a specific phenotype that should be thought of as a single problem and that therapy for this phenotype could be more effective than therapies for the separate components. Since it is well known that treating only depression with comorbid pain is extremely difficult and treating only chronic pain with comorbid depression is extremely difficult, there is some sense in the proposition that a treatment for this “triumvirate”as they term it, might be more effective.

1 Interactions of pain (VAS), depression (MADRAS), and perceived cognitive deficit tested with THINC-it

Cha et al. have chosen to look at the interrelationship of depression, chronic pain and cognitive deficits in a unique way. Part of the uniqueness is having a cohort of depressed subjects and also a cohort of “normal”subjects. The group recruited from a general population was as a normative standard to be compared to the depressed group. It appears that some of the motivation for the study was also the need to further test their package, THINC-it, for the evaluation of cognitive deficits but it is fortunate that they have chosen this paradigm. The THINC-it package is a composite of several validated tests for cognitive function that this group has previously validated as a package in a study that has been submitted elsewhere.

By dissecting the possible interactions of depression (MADRAS), pain (VAS), perceived cognitive deficit and tested cognitive deficit (THINC-it), Cha et al. have come up with some very interesting conclusions, some obvious, some not so obvious [1].

  1. Pain discriminates between the depressed group and the nondepressed group,

  2. Depression severity predicts VAS scores,

  3. VAS level predicts the perceived cognitive deficit,

  4. VAS level predicts depression severity,

  5. This effect is cancelled out if one corrects for depression,

  6. Depression severity predicts perceived cognitive deficit,

  7. Perceived cognitive deficit predicts measured cognitive deficit,

  8. The combination of VAS plus perceived cognitive deficit is an even stronger prediction of measured cognitive deficit.

2 Perceived cognitive deficit is a hallmark of fibromyalgia (“Fibrofog”), but is present also in other chronic pain conditions

Much of this, i.e. the depression/pain interdependence, is not new [2]. However, the information concerning cognitive deficits is quite valuable in another way for those working with patients with both depression and pain. For many years, clinicians treating chronic pain were skeptical that patients with, for example fibromyalgia, actually had the cognitive deficits that they complained about until more sensitive testing was done. Now perceived cognitive deficits are felt to be a hallmark of fibromyalgia and are included in newer diagnostic protocols. Perceived cognitive deficits seem to be worse with higher pain levels in fibromyalgia as well as in this study’s depressed cohort. Here we have some very strong evidence to support the experience of not only fibromyalgia patients but also many others with chronic pain as well as depression. “I can’t think clearly”, “I have trouble concentrating”, “My memory is so bad”are very common comments from many pain patients with a variety of diagnoses. “Fibrofog”, as it is called in the fibromyalgia literature, is not restricted only to those with fibromyalgia [3].

3 Neuroanatomical overlap of pain, depression, and cognitive deficits

Cha et al. discuss the theory that the “triumvirate”of depression, pain and cognitive deficits is due to structural changes in the brain and that those changes overlap areas common to all three problems. There is some evidence for this neuroanatomically with newer scanning techniques as Cha et al. point out [1]. They also wonder about possible effects of “inflammation” (chronic neuroinflammation?) and the “opioidergic”systems on neuroanatomy. But structure and function are separate and one can also look at the depression/pain/cognitive deficit problem from a more dynamic functional point of view. With regard to function, there is an alternative explanation that could stand alone or be complimentary to the structural change theory. In this issue of the Scandinavian Journal of Pain and in a 2013 article in the Journal of Pain, Kolesar et al. have elegantly outlined the function of the Default Mode Network in pain [4,5]. Altered function of this network which has connectivity to the neuroanatomical structures cited by Cha et al. could also explain the depression, pain, cognitive deficit codependence [1]. It is very likely that both structure and function are involved and these two cannot be separated [6,7].

Cha et al. point out that medications for both pain and depression can cause cognitive deficits as a side effect. Although the article does not include a list of medications and dosages, the authors remark that the subjects in the depression group were remarkably free from or had only low doses of medications and feel that this could not explain the cognitive deficits [1].

4 Successful treatment of both pain and depression should improve cognitive dysfunction

I agree with their conclusion, where Cha et al. emphasize that for patients with depression, simultaneous treatment of pain is needed because of their findings of comorbidity in their subject group of depressed patients [1]. They also suggest that treating both problems would improve the cognitive dysfunction that accompanies both states. Studies from the Default Mode Network literature actually support this. Several studies demonstrate that successful treatment for pain (medications, cognitive behavioural therapy, and spinal cord stimulation) actually resets the Default Pain Network back to normal functioning and it would be interesting to look at the same information from successful treatment for depression. Evaluation of cognitive function with THINC-it and the connectivity of the Default Mode Network with fMRI in future studies should give us some interesting new information.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2016.12.004.

Multidisciplinary Pain Center, Academic Hospital, 75185 Uppsala, Sweden. Fax: +46 18 503539.

  1. Conflict of interest: None declared

References

[1] Cha DS, Carmona NE, Mansur RB, Lee Y, Park HJ, Rodrigues NB, Subramaniapillai M, Rosenblat JD, Pan Z, Lee JH, Lee JG, Almatham F, Alageel A, Shekotikhina M, Zhou AJ, Rong C, Harrison J, McIntyre RS. Pain and major depressive disorder: associations with cognitive impairment as measured by the THINC-integrated tool (THINC-it). Scand J Pain 2017;15:62–7.Search in Google Scholar

[2] Goesling J, Clauw DJ, Hassett AL. Pain and depression: an integrative review of neurobiological and psychological factors. Curr Psychiatry Rep 2013;15:421.Search in Google Scholar

[3] Kravitz HM, Katz RS. Fibrofog and fibromyalgia: a narrative review and implications for clinical practice. Rheumatol Int 2015;35:1115–25.Search in Google Scholar

[4] Kornelsen J, Sboto-Frankenstein U, McIver T, Gervai P, Wacnik P, Berrington N, Tomanek B. Default mode network functional connectivity altered in failed back surgery syndrome. J Pain 2013;14:483–9.Search in Google Scholar

[5] Kolesar TA, Bilevicius E, Kornelsen J. Salience, central executive and sensorimotor functional connectivity alterations in failed back surgery syndrome. Scand J Pain 2017;15:10–4.Search in Google Scholar

[6] Brodal AP. A neurobiologist’s attempt to understand persistent pain. Scand J Pain 2017;15:140–7.Search in Google Scholar

[7] Butler S. Important new insight in pain and pain-treatment induced changes in functional connectivity between the Pain Matrix and the Salience-, Central Executive-, and Sensorimotor-networks. Scand J Pain 2017;16:64–5.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.2017.03.004

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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