Saturday, October 03, 2009

It Hurts Less When I Can See It


Fig. 1 (Longo et al., 2009). The mirror box technique in which the subject has the experience of viewing their right hand, while in fact seeing their left hand reflected in a mirror.

Sight modifies somatosensation, by either enhancing or diminishing the subjective intensity of touch (Kennett et al., 2001) and pain (Ramachandran & Altschuler, 2009), respectively. These phenomena provide fascinating and lesser studied examples of crossmodal integration, or how signals from one sensory modality are combined with those of another to produce a unified percept. In an elegant series of experiments by Longo and colleagues, subjects who could see their own hand (either in a mirror or the real thing) reported less pain when exposed to the heat of a laser.


Laser ‘Pain Beam’ under development by the U.S. military. NOT used in the "elegant" laser evoked potential experiments.

Furthermore, an electrophysiological marker of pain was attenuated. This was measured from the EEG, time-locked to the application of the painful laser heat. These stimuli elicit a specific type of EEG response, called laser evoked potentials (LEPs). A sequence of three LEPs is generated in rapid succession, within the first 400 milliseconds after laser stimulation. These responses are called the N1, N2 and P2 potentials. 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. These electrophysiological responses are modulated by stimulus-driven and, even more extensively, top-down processes.
These top-down processes include things like attention, expectation, and perhaps input from other sensory modalities. One advantage of LEPs is that you can determine exactly when in the pain processing stream these influences are active. Of greatest interest in this context is the N2-P2 complex, recorded at 195 milliseconds and 375 milliseconds after stimulation.


Fig. 5 (Longo et al., 2009). Grand mean LEPs recorded from electrode Cz in the three experiments and N2/P2 peak-to-peak amplitudes at Cz (bottom right). Error bars are 1 SEM.

The results demonstrated a cool new form of visually induced analgesia:
Looking at one's hand produced significant reductions of subjective intensity and unpleasantness of laser pain and in the amplitude of the N2/P2 complex.... These effects were observed both when the illusion of looking directly at the hand was induced with a mirror box (Exps. 1 and 3) and when participants viewed their hand directly during stimulation (Exp. 2). The reduction was specific to seeing one's own hand (Exp. 3).
What is the mechanism of action for these effects? First it's useful to know where in the brain the N2-P2 signals arise, because you can't tell from EEG alone. Plaghki and Mouraux review evidence from dipole models and invasive recordings, which have
consistently revealed the activation of an extensive bilateral cortical network, comprising the secondary somatosensory cortex (S2), the insular cortex and the anterior cingulate cortex.
It is noteworthy that the N1 response prior to the N2-P2 complex (not discussed here) is insensitive to the attentional and cognitive manipulations that affect the latter.

But how does visual input influence pain processing in the insula and anterior cingulate? How does this crossmodal inhibition occur? This is tricky, because any coherent explanation would have to account for visual enhancement of touch perception. Longo and colleagues speculate that inhibitory GABA-containing neurons might be responsible:
Could a common mechanism produce such divergent effects on touch and pain? One possibility would be a visually induced crossmodal activation of GABAergic interneurons. Injection of GABA antagonists increases the size of SI tactile receptive fields, suggesting that GABAergic interneurons function to sharpen tactile receptive fields, increasing tactile acuity. Conversely, GABA agonists are effective treatments for chronic central pain, suggesting that reduced GABAergic inhibition may be a major cause of chronic pain...

Both the present results showing analgesic effects of seeing the body and previous findings showing tactile enhancement (Kennett et al., 2001) could therefore be explained by visual modulation of somatosensory GABAergic interneurons. This speculation is supported by multisensory influences on cortical inhibition in other physiological systems. For example, viewing a hand extends the TMS-evoked silent period compared with viewing a fixation cross.
A related phenomenon was described by Mo Costandi in Distorting the body image affects perception of pain. Here, chronic pain patients viewed either magnified or "minified" versions of their affected arm while carrying out standarized motions. Subjective pain ratings were reported to be magnified or minified accordingly.

Finally, looking at images other than of one's own body can affect the perception of pain as well. For instance, viewing aesthically pleasing art during the application of laser heat stimuli reduced pain ratings and LEP amplitudes (de Tommaso et al., 2008), as covered by The Neurocritic in Pain & Paintings: Beholding Beauty Reduces Pain Perception and Laser Evoked Potentials.

In conclusion, Longo et al. note their results have possible implications for non-pharmacological treatments for pain:
First, the present results show an analgesic effect of vision of the body for acute, rather than chronic, pain. Second, several authors have suggested that mirror therapy may operate by promoting plastic reorganization within somatosensory map or by correcting a distorted body image through visual recalibration of proprioception [e.g. Ramachandran & Altschuler, 2009], yet our results demonstrate analgesic effects of seeing the body in healthy participants without body image distortion. Third, previous studies have generally involved voluntary movement of the unaffected limb, inducing the illusion of control over the affected hand. Therapeutic effects are typically attributed to the mirror-induced match between visually perceived movement and efferent commands specifying movement. The present results, however, suggest that qualitatively similar analgesic effects may result from simply seeing the hand, independent of movement or match between efferent and afferent signals.
Another application might be for the increasingly popular laser tattoo removal industry. Would having the client view the tattooed body part during the procedure lessen the perception of pain? Anyone who has tried (or would like to try) this experiment, please leave a comment on this post.



For the full on laser pain experience, watch Tattoo removal, no numbing cream. It's a straight edge dude getting XPROVENX removed from his neck. Other than screaming, his harshest utterance is "oh my gosh!"

References

de Tommaso M, Sardaro M, Livrea P. (2008). Aesthetic value of paintings affects pain thresholds. Conscious Cogn. 17:1152-62.

Kennett S, Taylor-Clarke M, Haggard P (2001). Noninformative vision improves the spatial resolution of touch in humans. Curr Biol 11:1188–1191.

Longo, M., Betti, V., Aglioti, S., & Haggard, P. (2009). Visually Induced Analgesia: Seeing the Body Reduces Pain. Journal of Neuroscience, 29 (39), 12125-12130. DOI: 10.1523/JNEUROSCI.3072-09.2009

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

Ramachandran VS, Altschuler EL. (2009). The use of visual feedback, in particular mirror visual feedback, in restoring brain function. Brain 132:1693-710.

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9 Comments:

At October 04, 2009 12:41 PM, Anonymous Anonymous said...

I am extensively tattooed. I can attest to the premise that _getting_ a tattoo hurts much less when you can observe the process. When I cannot see the needles about to touch down the pain when they do increases by about 1/3. Once the needles are working, whether or not I look, even high levels of pain are manageable.

Christ Davis

 
At October 04, 2009 2:21 PM, Anonymous P. Jennings said...

Neurocritic,

Have you seen the work relating to phantom pain?

http://aig.cs.man.ac.uk/research/phantomlimb/phantomlimb.php

" . . . .Ramachandran created a mirror box made by placing a vertical mirror inside a cardboard box with the top removed, in which the amputee places their remaining anatomical limb inside and views a reflection in the visual space occupied by their phantom limb.

"He reports anecdotal evidence that the box was able to induce in patients vivid sensations of movement originating from the muscles and joints of their phantom limb. For some patients their phantom limb pain was relieved and others were able to gain control over 'paralysed' phantoms'.

"The mirror box has also recently been used with similar success with lower-limb amputees, where viewing a reflection of an anatomical limb in the phenomenal space of a phantom limb resulted in amputees reporting a significantly greater number of movements of their phantom limb than with attempted movement alone . . ."

 
At October 04, 2009 3:59 PM, Blogger The Neurocritic said...

Christ Davis - thanks for relaying your experience. I imagine many others have similar reports.

P. Jennings - thanks for the link, I have seen some of Ramachandran et al.'s work on phantom limb pain. There is currently a clinical trial in the US: Mirror Therapy for Phantom Limb Pain.

 
At October 04, 2009 7:30 PM, Anonymous Monado said...

In a very minor way, I've had the opposite experience of having an itch turn to pain when I looked and found the source was a fresh scratch oozing blood.

When I had minor surgery on one of my hands, I chose not to look.

 
At October 05, 2009 8:52 AM, Blogger ragamuffin said...

You know, the Longo et al study was done quite elegantly except for the reporting of the data, where I would have liked to see LEP representation from the specific areas mentioned in the methods:

"Two LEP components were investigated. First, the early, lateralized N1 potential, maximal over contralateral temporal electrodes, and originating from operculoinsular cortex (Garcia-Larrea et al., 2003Go), possibly including secondary somatosensory cortex (Spiegel et al., 1996Go; Frot et al., 1999Go). Second, the bipolar vertex N2/P2 complex. Intracranial recordings have linked the N2/P2 to parallel activations in at least three brain areas: SI, parasylvian, and cingulate cortices (Ohara et al., 2004Go). "

You highlighted Figure 5, which demonstrates electrode Cz means but nothing about which region of the cortex... which seems rather silly since the whole point of these experiments is to characterize whatever reallocation of mirror neurons is occurring across which regions in order to invoke the analgesic effect. Wouldn't you think?

 
At October 05, 2009 3:27 PM, Blogger The Neurocritic said...

Monado - one could easily believe that seeing blood and surgical procedures that compromise bodily integrity might have the opposite effect on pain.

ragamuffin - Longo et al. did not mention mirror neurons anywhere in their article. Neither did Plaghki and Mouraux (2005) in their the LEP review. Longo et al. don't illustrate the N1 (which would be shown at the T7 electrode and not at Cz). But they do say "No significant modulation of the N1 component was observed (mean ± SD: hand, –7.4 ± 4.3 µV object, –6.7 ± 2.5 µV; F(1,12) = 0.88)."

You can see N1 in the study of Tommaso et al., 2008, summarized in the post, Pain and Paintings... In that experiment N1 was not affected by aesthetically pleasing paintings, but N2-P2 complex was.

 
At October 05, 2009 6:08 PM, Blogger ragamuffin said...

yes. my point - perhaps unclear - was that given that the Longo et al experimental paradigms were based on the mirror-vision protocol developed by Ramachandran, it seems strange that they did not suggest any mirror neuron system involvement in their analgesic findings precisely because their study holds strong implications for supporting the role of these somatosensory and parietal circuits.

 
At October 05, 2009 7:11 PM, Blogger The Neurocritic said...

Rama is a notorious mirror neuron cheerleader: MIRROR NEURONS and imitation learning as the driving force behind "the great leap forward" in human evolution! Yay team!

Others are a little more circumspect about them (including me). As for mirror neuron activity being reflected in the LEPs, I don't think Mu waves map onto them all that well. According to Wikipedia, mu waves are

...electromagnetic oscillations in the frequency range of 8-13 Hz and appear in bursts of 9-11 Hz. Mu wave patterns arise from synchronous and coherent (in phase/constructive) electrical activity of large groups of neurons in the human brain. This wave activity appears to be associated with the motor cortex (central scalp), and is diminished with movement or an intent to move, or when others are observed performing actions. EEG oscillations in the mu wave range over sensorimotor cortex are thought to reflect mirror neuron activity.

The P2 in particular is too slow for the 8-13 Hz range. Then there's the small difference between neural activity related to movement vs. pain. Finally it seems the N2/P2 LEPs are generated in the anterior cingulate and the insula, neither of which are prime locations for mirror neurons. Perhaps the nearby operculum has them, by some accounts.

If I'm missing something, please let me know.

 
At March 08, 2010 6:14 AM, Blogger little_mis_star said...

Hi,

I'm having to critically evaluate the Longo Paper for my degree however i am struggling somewhat. The experiment they conducted seems sound.. i.e. they have used the laser appropriately. controlled for habituation etc but supposedly i'm searching for the interpretations they have made not being valid? Does anyone have any thoughts on this?
Thanks

 

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