The Neurophysiology of Pain During REM Sleep

In the last post, we learned about The Phenomenology of Pain During REM Sleep. Real life pain can intrude into dreams, as was shown for experimentally induced pain (Nielsen et al., 1993) and in hospitalized burn patients (Raymond et al., 2002). In this post we'll hear about a fascinating experiment that recorded laser evoked potentials directly from the brains of epilepsy patients who were being surgically monitored for seizures (Bastuji et al. 2011). Only under rare circumstances can intracranial electrodes be placed in the brains of humans, and the current study had the unique opportunity to record from three major pain regions simultaneously: the posterior insula (Brodmann area 13), the parietal operculum (somatosensory area S2), and the mid-anterior cingulate cortex (BA 24). These areas comprise the so-called "Pain Matrix"¹ (PM), or

network of cortical structures that respond consistently to noxious mechanical or thermal stimuli. The lateral structures of the PM (posterior insula and suprasylvian operculum) are thought to subserve intensity coding and localization of pain inputs, while the medial PM system (anterior and mid-cingulate cortex) is linked to the attentional (orienting and arousing) components of pain.

In the present study, Bastuji et al. (2011) recorded laser evoked potentials (LEPs) from these brain regions during different stages of sleep, as well as while the patients were awake. LEPs are a specific type of EEG response time-locked to the application of painful laser heat stimuli. When recorded from the scalp, a sequence of three LEPs is generated in rapid succession, within the first 400 milliseconds after laser stimulation. As described in a review by Plaghki and Mouraux (2005),

Laser heat stimulators selectively activate Aδ and C-nociceptors ["pain receptors"] in the superficial layers of the skin. Their high power output produces steep heating ramps, which improve synchronization of afferent volleys and therefore allow the recording of time-locked events, such as laser-evoked brain potentials. Study of the electrical brain activity evoked by Aδ- and C-nociceptor afferent volleys revealed the existence of an extensive, sequentially activated, cortical network.

The advantage of recording intracranial LEPs is that you know precisely when the pain-related activity occurred, as well as where the brain response was located (unlike with standard EEG). Two major components were observed: Component 1 (C1), peaking at ~200 ms post-stimulus and Component 2 (C2), peaking at ~300 ms. Because the components were of varying polarities depending on brain region, they weren't labelled according to the customary N2/P2 as seen on the scalp. Of primary interest was what happened to these components during Stage 2 sleep and REM sleep (see Fig. 3A below).


Figure 3A (modified from Bastuji et al. 2011). Grand average LEPs in referential recording mode during wakefulness, sleep stage 2, and paradoxical sleep in the operculum (bottom), the insula (middle), and the mid-anterior cingulate (top). Traces recorded by the electrode contact yielding the largest amplitudes are superimposed on those from the adjacent contact. On the left part of the figure, for each structure, the coordinates of the contacts where the maximal amplitudes of the C1–C2 components were recorded are indicated on mean sagittal MRIs.


Typically, painful stimuli at the nociceptive threshold will cause awakening ~30% of the time. In this study, the stimulus intensity of the laser² was set individually in each participant to be slightly above pain threshold. C1 and C2 decreased in amplitude in all three brain regions during Stage 2 sleep, relative to wakefulness. During REM sleep, however, both components remained stable in amplitude (relative to Stage 2) in the operculum and insula, but they decreased dramatically in the cingulate. Recall that the medial mid-anterior cingulate cortex (ACC) is associated with the attentional and affective components of pain, while the lateral opercular and insular cortices are more related to the sensory aspects of pain. The authors suggest that this dissociation between the lateral and medial pain systems is what allows the experience of pain in dreams without being alerted enough to wake up. The fact that larger mid-ACC LEPs can predict when motor responses to pain will occur supports this interpretation.


CODA (Notes from an Actual Pain Dream)

Lately I've had a painful orthopedic issue (in real life). I also have a cat who is fond of laying on my legs at night, which is not comfortable at all under the circumstances. Yesterday morning, I had a terrible nightmare in which my real life leg pain was projected onto someone else in an exceptionally gruesome way. I was driving along an unknown neighborhood street when suddenly a man appeared in front of my car. It wasn't clear if he was on the hood or on the trunk of the car ahead of me or suspended in the air in a dream-like way. At any rate, if that wasn't bad enough, he pulled up the body of a man who had fallen under my car and had both his legs amputated from being run over -- one leg was amputated below the knee, the other was at the hip. The gravely injured man was still alive. I was absolutely horrified. All I could do is say "oh my god oh my god oh my god" over and over. At some point my car rolled backward down a steep hill and the other motorists behind me were exclaiming "oh my god oh my god" as well.

It was an awful nightmare, and in the dream I was quite traumatized by the entire experience. Did I feel excruciating pain when I woke up? No, not really, just the usual ache.


Further Reading

LEPs and pain perception can be reduced while looking at one's own hand or at beautiful artwork:

It Hurts Less When I Can See It

Pain & Paintings: Beholding Beauty Reduces Pain Perception and Laser Evoked Potentials

Footnotes

¹ "So-called" because the Pain Matrix might not be that specific to nociception after all (Iannetti & Mouraux, 2010).

² Laser pulses were delivered to the back of the hand opposite to the hemisphere with the implanted electrodes.

References

Bastuji, H., Mazza, S., Perchet, C., Frot, M., Mauguière, F., Magnin, M., & Garcia-Larrea, L. (2011). Filtering the reality: Functional dissociation of lateral and medial pain systems during sleep in humans. Human Brain Mapping DOI: 10.1002/hbm.21390

Iannetti GD, Mouraux A. (2010). From the neuromatrix to the pain matrix (and back). Exp Brain Res. 205:1-12.

Nielsen TA, McGregor DL, Zadra A, Ilnicki D, & Ouellet L (1993). Pain in dreams. Sleep 16:490-8.

Plaghki L, Mouraux A. (2005). EEG and laser stimulation as tools for pain research. Curr Opin Investig Drugs 6:58-64. PDF

Raymond I, Nielsen TA, Lavigne G, Choinière M. (2002). Incorporation of pain in dreams of hospitalized burn victims. Sleep 25:765-70.