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Analysis of C-reactive protein (CRP) levels in pain patients – Can biomarker studies lead to better understanding of the pathophysiology of pain?

  • Torsten Gordh EMAIL logo
Veröffentlicht/Copyright: 1. April 2016
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Scandinavian Journal of Pain
Aus der Zeitschrift Scandinavian Journal of Pain Band 11 Heft 1

In this issue of the Scandinavian Journal of Pain, Michele Sterling and co-authors present data showing that blood levels of the inflammatory biomarker serum C-reactive protein (CRP) seem to correlate to fMRI responses in regional brain areas, activated by noxious cold stimulation of the hand in patients with chronic whiplash associated disorders (WAD) [1]. The activated brain regions included the anterior insula, posterior parietal cortex, caudate and thalamus. The levels of TNF-alpha were not related to cerebral fMRI changes during pain stimuli, but a moderate positive correlation was found between blood levels of TNF and the psychological variable of pain catastrophizing.

The study shows the interesting possibility to use analysis of biomarkers in blood as a way for deeper understanding of the biological aspect of pain, this elusive “bio-psycho-social” construct, combined with “imaging biomarkers” using fMRI.

I think it is realistic to say that in the parts of the medical community, pain patients and pain treatment often are considered as “low status” work, and difficult to handle. One reason behind this view may be the fact that the golden standard of pain assessment is based upon the patient’s self-report only, and that objective, measurable findings usually are absent. Of course, we must trust the patient’s report, but I often wish that we had better tools to understand the nature of pain and its pathophysiology.

“We need a CRP for pain”, a colleague pain clinician once said, “some lab test that would show that there is something measurable going on in the pain patient. This would improve the respect for the pain patients from the caregivers, and give the field of pain medicine a better status” (personal communication, Jens Draiby, 2014).

It is not realistic to believe that we can measure the actual pain experience through biomarker studies, since pain by definition is a subjective experience that cannot be measured that way. But, perhaps biomarker studies in body fluids (e.g. blood, CSF, saliva, or micro dialysate from painful tissue) can help us to better understand 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? Virtually all other medical specialties have a foundation in analysis of biomarkers for diagnosis of diseases, and as a guide for treatment choice, and treatment effects. Still, biomarker research in pain patients is, by large, “terra incognita”, but we would certainly need more of this in our work to help pain patients better.

The cause of elevated CRP levels in patients with chronic WAD is not clear. What is the chain of events, starting with a WAD injury that may lead to increased production of CRP in the liver? It may be as a result of unresolved peripheral tissue damage in cervical spinal structures [2], resulting in a subclinical systemic inflammatory response including release of CRP. The analysis of CRP gives only limited information about on-going inflammatory processes. The use of more sensitive analytic tools for detection of inflammation, recently available, such as multiplex arrays for the multitude of mediators involved in the inflammatory cascade [3], may provide more detailed information on these complex events.

The study design and the methods used by Sterling et al. are advanced - selecting a clinical pain state (WAD), investigating the blood levels of inflammatory markers, and study possible correlations of cold stimuli and brain activation using fMRI in the same patient. Possible connections between levels of inflammatory biomarkers and psychological factors were also looked for, as an interesting attempt to “unite” psychological issues to biology. There are also some limitations of the present study. The number of subjects included in the study is small, including only patients and no controls. The levels of inflammatory biomarkers were not corrected for influences of body mass, which may be of importance.

Nevertheless, the study by Sterling et al. [1] indicates that research on inflammatory biomarkers in pain patients may contribute to a better understanding of the biological aspects of the complex pathophysiology of pain. It is a good early attempt in the search for the “CRP for pain patients”.

DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2015.11.003.

  1. Conflict of interest: None declared by the author.

References

[1] Sterling M, Head J, Cabot PJ, Farrell M. Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders. Scand J Pain 2016;11:19–26, http://dx.doi.org/10.1016/j.sjpain.2015.11.003Suche in Google Scholar

[2] Linnman C, Appel L, Fredrikson M, Gordh T, Soderlund A, Langstrom B, Engler H. Elevated [11C]-D-deprenyl uptake in chronic Whiplash Associated Disorder suggests persistent musculoskeletal inflammation. PLoS ONE 2011;6:e19182, http://dx.doi.org/10.1371/journal.pone.0019182.Suche in Google Scholar

[3] Lind AL, Wu D, Freyhult E, Bodolea C, Ekegren T, Larsson A, Gustafsson MG, Katila L, Bergquist J, Gordh T, Landegren U, Kamali-Moghaddam M. A multiplex protein panel applied to cerebrospinal fluid reveals three new biomarker candidates inALS but none in neuropathic pain patients. PLoS ONE 2016;11:e0149821, doi:0.1371/journal.pone.0149821.Collection 2016.doi:0.1371/journal.pone.0149821.Collection 2016Suche in Google Scholar
Published Online: 2016-04-01
Published in Print: 2016-04-01

© 2016 Scandinavian Association for the Study of Pain

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  2. Psychophysiological effects of threatening a rubber hand that is perceptually embodied in healthy human subjects
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https://doi.org/10.1016/j.sjpain.2016.03.002

Artikel in diesem Heft

  1. Editorial comment
  2. Psychophysiological effects of threatening a rubber hand that is perceptually embodied in healthy human subjects
  3. Original experimental
  4. A preliminary investigation into psychophysiological effects of threatening a perceptually embodied rubber hand in healthy human participants
  5. Editorial comment
  6. Analysis of C-reactive protein (CRP) levels in pain patients – Can biomarker studies lead to better understanding of the pathophysiology of pain?
  7. Clinical pain research
  8. Serum C-reactive protein levels predict regional brain responses to noxious cold stimulation of the hand in chronic whiplash associated disorders
  9. Editorial comment
  10. Importance of early diagnosis of complex regional pain syndrome (CRPS-1 and CRPS-2): Delayed diagnosis of CRPS is a major problem
  11. Clinical pain research
  12. Delayed diagnosis and worsening of pain following orthopedic surgery in patients with complex regional pain syndrome (CRPS)
  13. Editorial comment
  14. Associative learning mechanisms may trigger increased burden of chronic pain; unlearning and extinguishing learned maladaptive responses should help chronic pain patients
  15. Original experimental
  16. When touch predicts pain: predictive tactile cues modulate perceived intensity of painful stimulation independent of expectancy
  17. Editorial comment
  18. Low back pain among nurses: Common cause of lost days at work and contributing to the worldwide shortage of nurses
  19. Observational study
  20. Pain-related factors associated with lost work days in nurses with low back pain: A cross-sectional study
  21. Editorial comment
  22. Assessment of persistent pelvic pain after hysterectomy: Neuropathic or nociceptive?
  23. Clinical pain research
  24. Characterization of persistent pain after hysterectomy based on gynaecological and sensory examination
  25. Editorial comment
  26. Transmucosal fentanyl for severe cancer pain: Nasal mucosa superior to oral mucosa?
  27. Original experimental
  28. Facilitation of accurate and effective radiation therapy using fentanyl pectin nasal spray (FPNS) to reduce incidental breakthrough pain due to procedure positioning
  29. Editorial comment
  30. Why do we have opioid-receptors in peripheral tissues? Not for relief of pain by opioids
  31. Clinical pain research
  32. Peripheral morphine reduces acute pain in inflamed tissue after third molar extraction: A double-blind, randomized, active-controlled clinical trial
  33. Editorial comment
  34. Chronic pain and psychological distress among long-term social assistance recipients – An intolerable burden on those on the lowest steps of the socioeconomic ladder
  35. Clinical pain research
  36. The co-occurrence of chronic pain and psychological distress and its associations with salient socio-demographic characteristics among long-term social assistance recipients in Norway
  37. Editorial comment
  38. Fifty years on the Visual Analogue Scale (VAS) for pain-intensity is still good for acute pain. But multidimensional assessment is needed for chronic pain
  39. Clinical pain research
  40. Patient reported outcome measures of pain intensity: Do they tell us what we need to know?
  41. Editorial comment
  42. Postoperative pain documentation 30 years after
  43. Topical review
  44. Postoperative pain documentation in a hospital setting: A topical review
  45. Editorial comment
  46. Aspects of pain attitudes and pain beliefs in children: Clinical importance and validity
  47. Observational study
  48. The Survey of Pain Attitudes: A revised version of its pediatric form
  49. Editorial comment
  50. The role of social anxiety in chronic pain and the return-to-work process
  51. Clinical pain research
  52. Social Anxiety, Pain Catastrophizing and Return-To-Work Self-Efficacy in chronic pain: a cross-sectional study
  53. Editorial comment
  54. Advances in understanding and treatment of opioid-induced-bowel-dysfunction, opioid-induced-constipation in particular Nordic recommendations based on multi-specialist input
  55. Topical review
  56. Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction–Recommendations of the Nordic Working Group
  57. Observational study
  58. Opioid-induced constipation, use of laxatives, and health-related quality of life
  59. Editorial comment
  60. Migraine headache and bipolar disorders: Common comorbidities
  61. Systematic review
  62. Migraine headache and bipolar disorder comorbidity: A systematic review of the literature and clinical implications
  63. Editorial comment
  64. The role of catastrophizing in the pain–depression relationship
  65. Clinical pain research
  66. The mediating role of catastrophizing in the relationship between pain intensity and depressed mood in older adults with persistent pain: A longitudinal analysis
  67. Announcement
  68. May 26-27, 2016 Scandinavian Association for the Study of Pain, Reykjavik, Iceland May 25, 2016 PhD course
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