Conditioned Pain Modulation

The human central nervous system has the ability to modulate pain sensation through processes of inhibition and excitation, by directional “top-down” (from cortical and sub-cortical areas / brainstem to spinal cord) or “bottom-up” (from the periphery to the spinal cord to the brain) mechanisms.

Endogenous pain inhibition often refers to central pain inhibition by the body. Conditioned Pain Modulation (CPM) is a term to describe one of the psychophysical paradigms in which central pain inhibition is tested by means of “pain inhibits pain”. The parallel phenomenon for CPM in animal models is called Diffuse Noxious Inhibitory Controls (DNIC)

Significance of conditioned pain modulation capacity

​There have been numerous studies in which CPM has been investigated in the healthy and in disease states.

Many of the results point to a difference in CPM capacity between patients suffering from pain syndromes and healthy controls. This has been observed in: irritable bowel syndrome, fibromyalgia, migraine, and osteoarthritis. In these pain syndromes, a less efficient CPM as compared to healthy controls has been noted.

To date, the relationship of causality between a deficient CPM response and idiopathic pain syndromes is not entirely clear. There is evidence pointing to CPM either being affected by pharmaceutical and physical interventions and that a certain CPM profile could be prognostic for treatment response to specific drugs, for the tendency to develop chronic pain after surgery, etc.

How CPM can be tested

In order to test the CPM capacity of an individual, two different stimuli are needed:

  • The test stimulus: This stimulus will be administered at least twice. Once on its own (stand-alone) before administering the conditioning stimulus, and once during or right after the conditioning stimulus.

  • The conditioning stimulus: This stimulus will be administered after first applying the test stimulus. Application of the conditioning stimulus is expected to affect the experience of pain of the test stimulus that is administered in parallel or after the conditioning stimulus.

In essence, the reaction to the test stimulus is the one that is measured and the delta in reported pain between the stand-alone test stimulus and the test stimulus under influence of the conditioning stimulus is “CPM response”.

CPM can be tested using various modalities as the test and the conditioning stimuli. There is currently no gold standard on how CPM should be performed.  To have a successful CPM testing, stimulus intensity and body location should be considered.

Advantages of testing CPM with Medoc devices

Using Medoc’s systems to test CPM has many benefits, among them:

  • Precise and repeatable stimuli with controlled intensity and timing.

  • Both test and conditioning stimuli can be either hot (up to 50 degrees C) or cold (down to 0 degrees C)

  • Recording of pain intensity via VAS ratings implemented in the software, or the dedicated CoVAS device, and optional automatic CPM delta calculation

  • Full and accurate synchronization between the test and the conditioning stimuli

  • Use of individualized pain intensity

  • Performing CPM in the fMRI environment

  • Applicability for different body sites, for both the test and the conditioning stimuli

  • Easy disinfection of the thermodes and the AlgoMed probe, hassle-free

Read more on this topic:

General information on CPM

​Yarnitsky, D., Granot, M., & Granovsky, Y. (2014). Pain modulation profile and pain therapy: between pro-and antinociception. Pain, 155(4), 663-665.‏ 

​Yarnitsky, D. (2015). Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain, 156, S24-S31.‏ 

​Lewis, G. N., Rice, D. A., & McNair, P. J. (2012). Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. The journal of pain, 13(10), 936-944.‏

​​​Reliability of CPM

​Kennedy, D. L., Kemp, H. I., Ridout, D., Yarnitsky, D., & Rice, A. S. (2016). Reliability of conditioned pain modulation: a systematic review. Pain, 157(11), 2410.‏

​Imai, Y., Petersen, K. K., Mørch, C. D., & Arendt Nielsen, L. (2016). Comparing test–retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli. Somatosensory & motor research, 33(3-4), 169-177.‏

​Gehling, J., Mainka, T., Vollert, J., Pogatzki-Zahn, E. M., Maier, C., & Enax-Krumova, E. K. (2016). Short-term test-retest-reliability of conditioned pain modulation using the cold-heat-pain method in healthy subjects and its correlation to parameters of standardized quantitative sensory testing. BMC neurology, 16(1), 125.

Examples of CPM with Medoc devices

CPM with two thermodes

​Geva, N., & Defrin, R. (2018). Opposite effects of stress on pain modulation depend on the magnitude of individual stress response. , (4), 360-371.

​Levy, D., Abdian, L., Dekel-Steinkeller, M., & Defrin, R. (2018). Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals. Cephalalgia, 38(7), 1307-1315.‏

CPM with AlgoMed as the test stimulus

​Alsouhibani, A., Vaegter, H. B., & Hoeger Bement, M. (2019). Systemic exercise-induced hypoalgesia following isometric exercise reduces conditioned pain modulation. Pain Medicine, 20(1), 180-190.‏

​Owens, M. A., Parker, R., Rainey, R. L., Gonzalez, C. E., White, D. M., Ata, A. E., … & Goodin, B. R. (2019). Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain. Journal of neurovirology, 25(1), 57-71.‏

CPM with a thermal test stimulus

​Horn-Hofmann, C., Capito, E. S., Wolstein, J., & Lautenbacher, S. (2019). Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain. Pain, 160(9), 2063-2071.‏ 

​Bitar, N., Marchand, S., & Potvin, S. (2018). Pleasant pain relief and inhibitory conditioned pain modulation: A psychophysical study. Pain Research and Management, 2018.‏

​CPM in the fMRI

​Kisler, L. B., Granovsky, Y., Coghill, R. C., Sprecher, E., Manor, D., Yarnitsky, D., & Weissman-Fogel, I. (2018). Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study. Pain, 159(12), 2667-2677.

​Clinical implications of CPM

​Yarnitsky, D., Granot, M., Nahman-Averbuch, H., Khamaisi, M., & Granovsky, Y. (2012). Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain, 153(6), 1193-1198.‏ 

Examples of CPM with Medoc devices

CPM with two thermodes

​Geva, N., & Defrin, R. (2018). Opposite effects of stress on pain modulation depend on the magnitude of individual stress response. , (4), 360-371.

​Levy, D., Abdian, L., Dekel-Steinkeller, M., & Defrin, R. (2018). Experimental evidence for weaker endogenous inhibition of trigeminal pain than extra-trigeminal pain in healthy individuals. Cephalalgia, 38(7), 1307-1315.‏

CPM with AlgoMed as the test stimulus

​Alsouhibani, A., Vaegter, H. B., & Hoeger Bement, M. (2019). Systemic exercise-induced hypoalgesia following isometric exercise reduces conditioned pain modulation. Pain Medicine, 20(1), 180-190.‏

​Owens, M. A., Parker, R., Rainey, R. L., Gonzalez, C. E., White, D. M., Ata, A. E., … & Goodin, B. R. (2019). Enhanced facilitation and diminished inhibition characterizes the pronociceptive endogenous pain modulatory balance of persons living with HIV and chronic pain. Journal of neurovirology, 25(1), 57-71.‏

CPM with a thermal test stimulus

​Horn-Hofmann, C., Capito, E. S., Wolstein, J., & Lautenbacher, S. (2019). Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain. Pain, 160(9), 2063-2071.‏ 

​Bitar, N., Marchand, S., & Potvin, S. (2018). Pleasant pain relief and inhibitory conditioned pain modulation: A psychophysical study. Pain Research and Management, 2018.‏

​CPM in the fMRI

​Kisler, L. B., Granovsky, Y., Coghill, R. C., Sprecher, E., Manor, D., Yarnitsky, D., & Weissman-Fogel, I. (2018). Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study. Pain, 159(12), 2667-2677.

​Clinical implications of CPM

​Yarnitsky, D., Granot, M., Nahman-Averbuch, H., Khamaisi, M., & Granovsky, Y. (2012). Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain, 153(6), 1193-1198.‏ 

Hear from the masters

​In-depth interview with Prof. David Yarnitsky on Conditioned Pain Modulation