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Differences in central pain modulation between patients with chronic pain are important determinants of clinical pain status



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Despite a better understanding of chronic pain during the last decade, treatment remains difficult and is often unsuccessful. Recent studies suggest that mechanisms of central pain modulation, (that is, mechanisms inside our central nervous system which can facilitate or inhibit our pain experience), play an important role in the development of chronic pain. However, knowledge on  how these central pain modulatory mechanisms relate to the level of daily pain in chronic pain patients is sparse.

In our recently published study [1] we investigated if and how central pain modulatory mechanisms related to clinical pain intensity, the number of painful body areas, sensitivity to pressure and heat stimuli, and psychological distress in a large cohort of patients,  with a variety of chronic pain conditions, who were referred to treatment at a pain clinic.

Pain facilitation can be evaluated by a phenomenon known as temporal summation of pain (TSP). It can be assessed by providing identical, repetitive painful pressure stimulations (e.g. on the leg); TSP is characterized by a subjective increase in pain intensity during the repetitive stimulations. Higher degrees of TSP are believed to represent increased sensitivity in the central pain mechanisms within the spinal cord. Conversely, pain inhibition is often evaluated using a phenomenon known as conditioned pain modulation (CPM). CPM is often assessed by recording pain thresholds to pressure (e.g. on the leg) before and during a painful conditioning stimulus (e.g. cold water or pressure) applied to the other leg. Lower degrees of CPM are believed to reflect reduced efficacy in the pain modulatory systems that inhibit the perception of pain.

We measured TSP, CPM, pain threshold, and pain tolerance on the leg using a computer-controlled pressure cuff algometer (a device that is somewhat similar to an advanced blood pressure machine). Additionally, we assessed pain thresholds to heat delivered to the primary painful area of the body and in a pain-free area. Finally, patients completed several questionnaires on pain intensity, pain distribution, level of disability, fear of movement and pain-related catastrophic thoughts.

For analyses, we grouped patients into four distinct groups based on whether patients demonstrated normal or facilitated TSP and normal or impaired CPM:

Group 1 (21.2% of patients, n=85) was characterized by an impaired CPM response and a facilitated TSP.

Group 2 (37.0% of patients, n=148) was characterized by an impaired CPM response and a normal TSP.

Group 3 (11.2% of patients, n=45) was characterized by a normal CPM response and a facilitated TSP.

Group 4 (30.5% of patients, n=122) was characterized by a normal CPM and a normal TSP.

We found that patients, irrespective of pain condition, that demonstrated facilitated TSP and impaired CPM (i.e., Group 1) had significantly more painful areas compared with other patients. We also found that patients with impaired CPM (i.e., Group 1 and 2) rated their clinical pain higher and were more sensitive to pressure and heat pain stimulations compared with patients with a normal CPM response (i.e., Group 3 and 4). Patients were not significantly different on demographics, disability, pain catastrophizing, and fear of movement.

The results from this study indicate that pain facilitatory and inhibitory systems are important determinants of pain status in patients with chronic pain. These findings could have important clinical implications as the effect of treatment strategies may differ depending on the individual’s level of pain facilitation and pain inhibition. Identification of these mechanisms in clinical practice may be a step forward towards individualized pain treatment.

Where to from here? To further elucidate the impact of the pain facilitatory and inhibitory systems in chronic pain, future studies should investigate whether treatments targeted to these subgroups, (e.g. treatments that reduce pain facilitation and/or improve pain inhibition), have better effects compared with current treatment guidelines.

About Henrik Bjarke Vægter

Henrik Bjarke VægterHenrik Bjarke Vægter is a Postdoctoral-fellow at the Department of Clinical Research, University of Southern Denmark and at the Pain Research Group, Pain Center South at Odense University Hospital in Denmark. He received his bachelor degree within Physiotherapy from University College Sealand, Denmark in 2004 and acquired a MSc degree within Pain Management in 2010 (Edinburgh University). In 2015 he obtained his Ph.D. degree from the Doctoral School in Medicine, Biomedical Science and Technology, Faculty of Medicine, Aalborg University. To strengthen the translation from research to clinical practice Henrik has implemented an electronic data gathering and management tool in pain centers across Denmark. His research focuses primarily on clinical and somatosensory manifestations of chronic pain as well as predictors for positive outcome after pain rehabilitation.


  1. Vaegter H.B., Graven-Nielsen T. Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity. Pain 2016;157:1480-1488.

Commissioning Editor:  Tasha Stanton

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