Conditioned pain modulation: A useful test paradigm in research and in clinical practice
-
Audun Stubhaug
und
Harald Breivik
In this issue of the Scandinavian Journal of Pain, Gullander et al. publish an interesting study [1] on how conditioning heat pain attenuate experimental muscle pain in men and women. Their main research question was whether the modulation of pain by a conditioning stimulus differed between males and females. Previous studies have shown conflicting results [2]. Conditioned pain modulation (CPM) [4] was previously called DNIC (diffuse noxious inhibitory control). The latter term is now reserved for specific lower brainstem mediated inhibitory mechanism that was described in animal research first by Le Bars et al. [3]. A number of different CPM-paradigms have been used, and in two recent articles it was shown how results can differ within the same subject depending on the choice of the conditioning stimulus (CS – that causes a CPM) or the test stimulus (TS – the effect of which is inhibited by the CPM) [5,6]. Several independent factors influence the CPM result, as reviewed by Matre [7].
Since muscular pain is common and a major reason for sick leave and disability, intramuscular stimulation as test stimulus has special interest. Gullander and her colleagues induced muscle pain with electrical stimulation via needles inserted in the tibialis anterior muscle, and they used 30 s of painful contact heat to the contralateral volar forearm as the conditioning stimulus. They carefully chose and executed their methods; thus, the conditioning stimulus was calibrated for each person to match pain intensity of 50 on a 0–100 Visual Analogue Scale and the test stimuli were a fixed ratio (1.1 and 1.6) of each individual’s pain threshold. Such individualization of the CPM paradigm must be important but is not in general use. Often all subjects in a study of CPM receive the same conditioning stimulus. This could mean that the conditioning stimulus is only slightly painful to some subjects and intolerable to others.
It is well known that excitatory and inhibitory effects on pain perception vary in women during their menstrual cycle [8]. Therefore, Gullander and colleagues were also careful and examined all women in the ovulatory phase of their menstrual cycle, i.e. days 12–14 after the first day of a menstruation [1].
Gullander and colleagues did not find any difference in CPM effect between men and women. This is in contrast to the majority of previous studies [2]. One reason for this discrepancy could be the CPM paradigm used by Gullander and her colleagues with an intra-muscular test stimulus. Another reason could be their careful testing of female subjects only during the ovulatory phase, the phase of the menstrual cycle that is expected to give highest CPM in women [8].
An additional interesting finding is the fact that 6 of 40 healthy volunteers were CPM non-responders. Are these subjects at risk for developing chronic pain because they have ineffective pain inhibiting mechanisms? We know that chronic pain patients in general when tested show less CPM than controls, but that CPM is particularly lacking in patients suffering from fibromyalgia, irritable bowel syndrome, and temporomandibular pain syndrome [9, 10, 11]. CPM – testing has been used to identify patients at high risk of having chronic pain after surgery and therefore should receive intensified treatment before, during, and after surgery [12]. Very interestingly, a recent article found that CPM was increased in pain patients after treatment with ketamine and to a lesser degree after morphine and placebo [13].
Gullander and her colleagues found that non-painful conditioning stimuli also caused a detectable, but smaller CPM-effect. This underscores the fact that CPM is a complex paradigm, and that emotional and contextual factors play important roles [14,15]. We need careful research, like the present study by Gullander et al. in order to find how CPM can be used in both research and in clinical practice.
DOI of refers to article: http://dx.doi.org/10.1016/j.sjpain.2012.04.006.
References
[1] Gullander M, Knardahl S, Matre D. Painful heat attenuates electrically induced muscle pain in men and women. Scand J Pain 2013;4:103–8.Suche in Google Scholar
[2] Popescu A, LeResche L, Truelove EL, Drangsholt MT. Gender differences in pain modulation by diffuse noxious inhibitory controls: a systematic review. Pain 2010;150:309–18.Suche in Google Scholar
[3] Le Bars D, Dickenson AH, Besson JM. Diffuse noxious inhibitory controls (DNIC) I: effects on dorsal horn convergent neurones in the rat. Pain 1979;6:283–304.Suche in Google Scholar
[4] Yarnitsky D, Arendt-Nielsen L, Bouhassira D, Edwards RR, Fillingim RB, Granot M, Hansson P, Lautenbacher S, Marchand S, Wilder-Smith O. Recommendations on terminology and practice of psychophysical DNIC testing. Eur J Pain 2010;14:339.Suche in Google Scholar
[5] Nahman-Averbuch H, Yarnitsky D, Granovsky Y, Gerber E, Dagul P, Granot M. The role of stimulation parameters on the conditioned pain modulation response. Scand J Pain 2013;4:10–4.Suche in Google Scholar
[6] Oono Y, Nie H, Matos RM, Wang K, Arendt-Nielsen L. The inter- and intra-individual variance in descending pain modulation evoked by different conditioning stimuli in healthy men. Scand J Pain 2011;2:162–9.Suche in Google Scholar
[7] Matre D. Conditioned pain modulation (CPM) is not one single phenomenon – large intra-individual differences depend on test stimulus (TS) and several other independent factors. Scand J Pain 2013;4:8–9.Suche in Google Scholar
[8] Tousignant-Laflamme Y, Marchand S. Excitatory and inhibitory pain mechanisms during the menstrual cycle in healthy women. Pain 2009;146:47–55.Suche in Google Scholar
[9] Lewis GN, Rice DA, McNair PJ. Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 2012;13:936–44.Suche in Google Scholar
[10] de Souza JB, Potvin S, Goffaux P, Charest J, Marchand S. The deficit of pain inhibition in fibromyalgia is more pronounced in patients with comorbid depressive symptoms. Clin J Pain 2009;25:123–7.Suche in Google Scholar
[11] King CD, Wong F, Currie T, Mauderli AP, Fillingim RB, Riley III JL. Deficiency in endogenous modulation of prolonged heat pain in patients with Irritable Bowel Syndrome and Temporomandibular Disorder. Pain 2009;143: 172–8.Suche in Google Scholar
[12] Yarnitsky D, Crispel Y, Eisenberg E, Granovsky Y, Ben-Nun A, Sprecher E, Best LA, Granot M. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk. Pain 2008;138:22–8.Suche in Google Scholar
[13] Niesters M, Aarts L, Sarton E, Dahan A. Influence of ketamine and morphine on descending pain modulation in chronic pain patients: a randomized placebo-controlled cross-over proof-of-concept study. Br J Anaesth 2013;(February(5)) [Epub ahead of print].Suche in Google Scholar
[14] Bjørkedal E, Flaten MA. Expectations of increased and decreased pain explain the effect of conditioned pain modulation in females. J Pain Res 2012;5:289–300.Suche in Google Scholar
[15] Nilsen KB, Christiansen SE, Holmen LB, Sand T. The effect of a mental stressor on conditioned pain modulation in healthy subjects. Scand J Pain 2012;3:142–8.Suche in Google Scholar
© 2013 Scandinavian Association for the Study of Pain
Artikel in diesem Heft
- Editorial comment
- From clear reporting to better research models
- Topical review
- Transparency in the reporting of in vivo pre-clinical pain research: The relevance and implications of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines
- Editorial comment
- Altered central pain processes behind fibromyalgia? Are they restored by antidepressants as indicated by an innovative fMRI-study?
- Clinical pain research
- Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia
- Editorial comment
- The obligation to publishing negative outcome data from neuropathic pain clinical trials
- Clinical pain research
- Evaluation of a novel chemokine receptor 2 (CCR2)-antagonist in painful diabetic polyneuropathy
- Editorial comment
- Chronic pain and mortality
- Clinical pain research
- Mortality rate and causes of death in women with self-reported musculoskeletal pain: Results from a 17-year follow-up study
- Editorial comment
- A novel approach of analyzing characteristics of sensory nerve fibers
- Original experimental
- Discriminative sensory characteristics of the lateral femoral cutaneous nerve after mepivacaine-induced block
- Editorial comment
- Conditioned pain modulation: A useful test paradigm in research and in clinical practice
- Original experimental
- Painful heat attenuates electrically induced muscle pain in men and women
- Editorial comment
- Amplification of osteoarthritis pain by peripheral and central nervous systems pain mechanisms
- Original experimental
- Relating clinical measures of pain with experimentally assessed pain mechanisms in patients with knee osteoarthritis
- Editorial comment
- The value of critical values from normative data
- Clinical pain research
- Percentile normative values of parameters of electrical pain and reflex thresholds
- Erratum
- Erratum to “Epithelial growth factor receptor (EGFR)-inhibition for relief of neuropathic pain–A case series” [Scand. J. Pain 4 (2013) 3–7]
Artikel in diesem Heft
- Editorial comment
- From clear reporting to better research models
- Topical review
- Transparency in the reporting of in vivo pre-clinical pain research: The relevance and implications of the ARRIVE (Animal Research: Reporting In Vivo Experiments) guidelines
- Editorial comment
- Altered central pain processes behind fibromyalgia? Are they restored by antidepressants as indicated by an innovative fMRI-study?
- Clinical pain research
- Using fMRI to evaluate the effects of milnacipran on central pain processing in patients with fibromyalgia
- Editorial comment
- The obligation to publishing negative outcome data from neuropathic pain clinical trials
- Clinical pain research
- Evaluation of a novel chemokine receptor 2 (CCR2)-antagonist in painful diabetic polyneuropathy
- Editorial comment
- Chronic pain and mortality
- Clinical pain research
- Mortality rate and causes of death in women with self-reported musculoskeletal pain: Results from a 17-year follow-up study
- Editorial comment
- A novel approach of analyzing characteristics of sensory nerve fibers
- Original experimental
- Discriminative sensory characteristics of the lateral femoral cutaneous nerve after mepivacaine-induced block
- Editorial comment
- Conditioned pain modulation: A useful test paradigm in research and in clinical practice
- Original experimental
- Painful heat attenuates electrically induced muscle pain in men and women
- Editorial comment
- Amplification of osteoarthritis pain by peripheral and central nervous systems pain mechanisms
- Original experimental
- Relating clinical measures of pain with experimentally assessed pain mechanisms in patients with knee osteoarthritis
- Editorial comment
- The value of critical values from normative data
- Clinical pain research
- Percentile normative values of parameters of electrical pain and reflex thresholds
- Erratum
- Erratum to “Epithelial growth factor receptor (EGFR)-inhibition for relief of neuropathic pain–A case series” [Scand. J. Pain 4 (2013) 3–7]
