COMMENTARY
The impact of the stimulation method on differences in pain thresholds and brain responses between chronic pain patients and healthy controls Accepted for publication 2 June 2014 doi:10.1002/ejp.565
In this issue you will find a paper by Franz et al. (2014) titled ‘Laser heat hyperalgesia is not a feature of nonspecific chronic low back pain’. In this study, 16 patients with chronic back pain and 16 healthy controls were stimulated with noxious laser heat. Laser heat pain thresholds and nociceptive laser-evoked electrical brain potentials following skin stimulation of the painaffected back and the pain-free abdomen were assessed. The surprising results of this study are that there were no significant differences between the groups in the laser heat pain thresholds and the nociceptive laser-evoked electrical brain potentials. This is in contrast to a large number of studies in different chronic pain disorders (e.g. fibromyalgia or chronic back pain) which report altered or more specifically augmented brain responses to painful stimulation. These studies used pressure, heat and incision stimuli to evoke the experimental pain. One reason for these differing results might be that there is considerably more spatial summation when using a thermode compared with laser stimulation. However, there were also studies using a CO2 laser which reported differences in pain thresholds and brain activation (Gibson et al., 1994; de Tommaso et al., 2011) in pain patients. Gibson et al. (1994) reported a significant reduction in the heat pain threshold on the dorsal surface of the hand in patients with fibromyalgia. Comparing stimulation at the intensity of the pain threshold and 1.5 times the pain threshold, patients with fibromyalgia showed increased peak to peak amplitude of the N270-P370 laser-evoked potential complex compared with healthy controls. In a recent study, de Tommaso et al. (2011) replicated these findings. They reported increased subjective pain intensity ratings of the laser pain and increased amplitude of the vertex N2-P2 complex as well as a decreased habituation in fibromyalgia. What are the differences between these studies and the study by Franz et al. (2014)? Especially important is the distinction of different pain disorders with localized pain in chronic back pain and wide spread pain in © 2014 European Pain Federation - EFIC®
fibromyalgia. Patients with fibromyalgia might have changes of the peripheral nervous system promoting sensitization using a stimulation method which induces less spatial summation. Since pain processing in both chronic back pain and fibromyalgia differ from healthy controls using other stimulation methods, a relevant factor could be the interstimulus interval of the experimental pain stimuli. For example, central sensitization could be prompted by the continuous nature of the stimulation in patients predisposed to acquire chronic pain. Patients and controls could process distinct stimuli similarly but at the same time process a series of fast successive stimuli or tonic stimulation different, due to plastic changes in chronic pain patients. A similar dissociation between phasic and tonic stimulation was previously reported in children who were exposed to pain around birth (Hermann et al., 2006). School-aged preterm and fullterm children with repeated pain experiences during the neonatal period showed enhanced perceptual thermal sensitization to tonic painful heat stimulation and hypoalgesia to brief heat pain stimuli compared with full-term children without pain experiences during the neonatal period. This may reflect both normal descending inhibition and sensitized ascending pain pathways and parallels animal data (Ren et al., 2004) suggesting that there might be alterations in antinociceptive mechanisms while other pronociceptive mechanisms may have been maintained. It is still an open question which stimulation parameters for each experimental painful stimulation method are necessary to find differences between patients and controls. On the other hand, it would be interesting to have parameters which are known to be processed similarly in both patients and controls. With such stimulation, the influence of emotional and cognitive evaluative aspects of pain processing could be investigated more precisely. It seems that it is not the question if chronic pain patients and controls differ from each other but rather which parameters are Eur J Pain 18 (2014) 1365–1366
1365
Commentary
needed to find the differences. From a physiological point of view, knowledge of the similarities and differences in pain processing could provide insights into the mechanisms underlying changes in the nervous system accompanied by the development of chronic pain. A study comparing the effects of different stimulation parameters for different methods is desperately needed. In conclusion, similarities in pain perception between patients and controls give as much insight into the mechanisms behind pain processing as differences between groups. Martin Diers Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health/Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Correspondence Martin Diers E-mail: [email protected]
1366 Eur J Pain 18 (2014) 1365–1366
Conflicts of interest None declared.
References de Tommaso, M., Federici, A., Santostasi, R., Calabrese, R., Vecchio, E., Lapadula, G., Iannone, F., Lamberti, P., Livrea, P. (2011). Laser-evoked potentials habituation in fibromyalgia. J Pain 12, 116–124. Franz, M., Ritter, A., Puta, C., Notzel, D., Miltner, W.H., Weiss, T. (2014). Laser heat hyperalgesia is not a feature of non-specific chronic low back pain. Eur J Pain 18, 1501–1508. Gibson, S.J., Littlejohn, G.O., Gorman, M.M., Helme, R.D., Granges, G. (1994). Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain 58, 185–193. Hermann, C., Hohmeister, J., Demirakca, S., Zohsel, K., Flor, H. (2006). Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain 125, 278–285. Ren, K., Anseloni, V., Zou, S.P., Wade, E.B., Novikova, S.I., Ennis, M., Traub, R.J., Gold, M.S., Dubner, R., Lidow, M.S. (2004). Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult. Pain 110, 588–596.
© 2014 European Pain Federation - EFIC®
The impact of the stimulation method on differences in pain thresholds and brain responses between chronic pain patients and healthy controls Accepted for publication 2 June 2014 doi:10.1002/ejp.565
In this issue you will find a paper by Franz et al. (2014) titled ‘Laser heat hyperalgesia is not a feature of nonspecific chronic low back pain’. In this study, 16 patients with chronic back pain and 16 healthy controls were stimulated with noxious laser heat. Laser heat pain thresholds and nociceptive laser-evoked electrical brain potentials following skin stimulation of the painaffected back and the pain-free abdomen were assessed. The surprising results of this study are that there were no significant differences between the groups in the laser heat pain thresholds and the nociceptive laser-evoked electrical brain potentials. This is in contrast to a large number of studies in different chronic pain disorders (e.g. fibromyalgia or chronic back pain) which report altered or more specifically augmented brain responses to painful stimulation. These studies used pressure, heat and incision stimuli to evoke the experimental pain. One reason for these differing results might be that there is considerably more spatial summation when using a thermode compared with laser stimulation. However, there were also studies using a CO2 laser which reported differences in pain thresholds and brain activation (Gibson et al., 1994; de Tommaso et al., 2011) in pain patients. Gibson et al. (1994) reported a significant reduction in the heat pain threshold on the dorsal surface of the hand in patients with fibromyalgia. Comparing stimulation at the intensity of the pain threshold and 1.5 times the pain threshold, patients with fibromyalgia showed increased peak to peak amplitude of the N270-P370 laser-evoked potential complex compared with healthy controls. In a recent study, de Tommaso et al. (2011) replicated these findings. They reported increased subjective pain intensity ratings of the laser pain and increased amplitude of the vertex N2-P2 complex as well as a decreased habituation in fibromyalgia. What are the differences between these studies and the study by Franz et al. (2014)? Especially important is the distinction of different pain disorders with localized pain in chronic back pain and wide spread pain in © 2014 European Pain Federation - EFIC®
fibromyalgia. Patients with fibromyalgia might have changes of the peripheral nervous system promoting sensitization using a stimulation method which induces less spatial summation. Since pain processing in both chronic back pain and fibromyalgia differ from healthy controls using other stimulation methods, a relevant factor could be the interstimulus interval of the experimental pain stimuli. For example, central sensitization could be prompted by the continuous nature of the stimulation in patients predisposed to acquire chronic pain. Patients and controls could process distinct stimuli similarly but at the same time process a series of fast successive stimuli or tonic stimulation different, due to plastic changes in chronic pain patients. A similar dissociation between phasic and tonic stimulation was previously reported in children who were exposed to pain around birth (Hermann et al., 2006). School-aged preterm and fullterm children with repeated pain experiences during the neonatal period showed enhanced perceptual thermal sensitization to tonic painful heat stimulation and hypoalgesia to brief heat pain stimuli compared with full-term children without pain experiences during the neonatal period. This may reflect both normal descending inhibition and sensitized ascending pain pathways and parallels animal data (Ren et al., 2004) suggesting that there might be alterations in antinociceptive mechanisms while other pronociceptive mechanisms may have been maintained. It is still an open question which stimulation parameters for each experimental painful stimulation method are necessary to find differences between patients and controls. On the other hand, it would be interesting to have parameters which are known to be processed similarly in both patients and controls. With such stimulation, the influence of emotional and cognitive evaluative aspects of pain processing could be investigated more precisely. It seems that it is not the question if chronic pain patients and controls differ from each other but rather which parameters are Eur J Pain 18 (2014) 1365–1366
1365
Commentary
needed to find the differences. From a physiological point of view, knowledge of the similarities and differences in pain processing could provide insights into the mechanisms underlying changes in the nervous system accompanied by the development of chronic pain. A study comparing the effects of different stimulation parameters for different methods is desperately needed. In conclusion, similarities in pain perception between patients and controls give as much insight into the mechanisms behind pain processing as differences between groups. Martin Diers Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health/Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Correspondence Martin Diers E-mail: [email protected]
1366 Eur J Pain 18 (2014) 1365–1366
Conflicts of interest None declared.
References de Tommaso, M., Federici, A., Santostasi, R., Calabrese, R., Vecchio, E., Lapadula, G., Iannone, F., Lamberti, P., Livrea, P. (2011). Laser-evoked potentials habituation in fibromyalgia. J Pain 12, 116–124. Franz, M., Ritter, A., Puta, C., Notzel, D., Miltner, W.H., Weiss, T. (2014). Laser heat hyperalgesia is not a feature of non-specific chronic low back pain. Eur J Pain 18, 1501–1508. Gibson, S.J., Littlejohn, G.O., Gorman, M.M., Helme, R.D., Granges, G. (1994). Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome. Pain 58, 185–193. Hermann, C., Hohmeister, J., Demirakca, S., Zohsel, K., Flor, H. (2006). Long-term alteration of pain sensitivity in school-aged children with early pain experiences. Pain 125, 278–285. Ren, K., Anseloni, V., Zou, S.P., Wade, E.B., Novikova, S.I., Ennis, M., Traub, R.J., Gold, M.S., Dubner, R., Lidow, M.S. (2004). Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult. Pain 110, 588–596.
© 2014 European Pain Federation - EFIC®
