We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli

Anna Losurdo

Catello Vollono

D Andress-Rothrock

D Borsook

Elisa Testani

G Della Marca

Giacomo Della Marca

M Engstrom

MT Smith

R Poryazova

Salvatore Mazza

SH Onen

Journal of Headache and Pain

English

PubMed

Vollono, Catello

Testani, Elisa

Losurdo, Anna

Mazza, Salvatore

Della Marca, Giacomo (ORCID:0000-0001-6914-799X)

PubliCatt

Vollono et al. The Journal of Headache and Pain 2013, 14:50http://www.thejournalofheadacheandpain.com/content/14/1/50LETTER TO THE EDITOR Open AccessMigraine, arousal and sleep deprivation:comment on: “sleep quality, arousal and painthresholds in migraineurs: a blinded controlledpolysomnographic study”Catello Vollono, Elisa Testani, Anna Losurdo, Salvatore Mazza and Giacomo Della Marca*AbstractWe discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation,which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have areduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows todump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed inMigraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation.The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep,and represents part of a more general vulnerability to incoming stimuli.Keywords: Migraine; Sleep; Sleep deprivation; Cyclic alternating pattern; Arousal; PainSir,We read with great interest the paper by Engstrøm et al.(2013) “Sleep quality, arousal and pain thresholds inmigraineurs: a blinded controlled polysomnographic study”[1]. We appreciated the methodology of the study, never-theless we believe that the hypothesis formulated by theAuthors in their conclusion deserves further comments.Findings1. In their study, the Authors evaluated psychophysio-logical measures and polisomnography (PSG) parametersin Migraineurs and healthy volunteers; in discussing theirresults, the Authors suggested the hypothesis thatMigraineurs have a relative sleep deprivation, which inturns lowers the pain threshold and predispose to head-ache attacks [1]. This hypothesis is theoretically conceiv-able, since it is based on solid data coming from Migraineand sleep literature. It is well known, in fact, that sleepdeprivation may enhance the response to pain stimuli [2];moreover, sleep restriction is one of the most commontriggers of migraine attacks [3].* Correspondence: dellamarca@rm.unicatt.itInstitute of Neurology, Catholic University, Policlinico Universitario ‘A.Gemelli’, Largo A. Gemelli, 8-00168, Rome, Italy© 2013 Vollono et al.; licensee Springer. This isAttribution License (http://creativecommons.orin any medium, provided the original work is p2. Nevertheless, other clinical and neurophysiological ob-servations are not in agreement with the Authors’ hypoth-esis. In fact, some data indicate that it is sleep continuitydisturbance, rather than simple sleep restriction, that im-pairs endogenous pain-inhibitory function and increasesspontaneous pain [4]. Moreover, it is likely that modifica-tion of routinely sleep habits is the major trigger, since in-creased sleep duration predisposes to Migraine attacks tothe same extent as sleep deprivation [3].3. The results of subjective (logs) and objective (PSG)sleep analysis reported by Engstrøm et al. (2013) [1] do notseem to be fully consistent with their hypothesis that‘migraineurs on the average suffer from a relative sleepdeprivation and need more sleep than healthy controls’. Infact, in their paper, Migraineurs showed an average totalsleep time slightly longer than controls, even though no sta-tistically significant differences were observed betweenMigraineurs and Controls in sleep macrostructure. Eventhe analysis of the sleep logs does not support thedeprivation hypothesis, since Migraineurs and controls hadsimilar average sleep time.4. Conversely, the Authors observed in Migraineurs a de-crease of fast arousal index, associated with an increase ofawakenings. This finding, apparently contradictory, isan Open Access article distributed under the terms of the Creative Commonsg/licenses/by/2.0), which permits unrestricted use, distribution, and reproductionroperly cited.Vollono et al. The Journal of Headache and Pain 2013, 14:50 Page 2 of 2http://www.thejournalofheadacheandpain.com/content/14/1/50similar to that reported in a previous study of our group[5]. In that paper [5] we studied a selected population ofsleep-related Migraineurs and we observed a reduction ofthe Cyclic Alternating Pattern (CAP). Therefore, we sug-gested that the slow-frequency, high-amplitude arousal fluc-tuations described in the CAP model are also essential todump the effect of incoming disruptive stimuli, and to pro-tect sleep from external perturbations. The impairment ofthis mechanism makes Migraineurs more vulnerable tostimuli triggering attacks during sleep.Discussion: alternative hypothesisOn the other hand, CAP modifications similar to those de-scribed in Migraineurs have been reported in normal sub-jects following sleep deprivation. Poryazova et al. (2011) [6]investigated the regulation NREM sleep in normal subjectand narcolepsy / cataplexy patients before and after sleepdeprivation. This study [6] demonstrated that: 1) patientswith impaired arousability (narcolepsy patients) have lowerCAP rate that controls; and 2) sleep deprivation induces areduction of CAP rate, which, in normal subjects afterdeprivation, reached values similar to those reported in ourstudy for Migraineurs.Whatever the interpretation, we believe that these data,taken together, suggest that Migraine is a condition inwhich an impairment of arousal responses occurs. As sug-gested by Borsook et al. (2012), Migraine is associated withalterations in normal homeostatic mechanisms (e.g., alteredsleep, abnormal autonomic function). When stressors be-come frequent and/or severe, allostatic responses may bedysregulated and become maladaptive (“allostatic load”).Such allostatic load, in turn, may alter brain responses tostressors; therefore, behavior and systemic physiology arealtered in ways that can, in a vicious cycle, lead to furtherallostatic load [7]. In this sense, arousals during sleep mustbe considered as an homeostatic, adaptive response, ratherthan a ‘pathologic’, disruptive phenomenon, which can bedetrimental for sleep. The impaired arousability duringsleep, seen in this view, is part of a more general decreasedability of Migraineurs to process incoming stimuli.AbbreviationsCAP: Cyclic alternating pattern; NREM: Non rapid eye movement;PSG: Polysomnography.Competing interestsThe authors declare that they have no competing interests.Authors’ contributionsCV: data analysis and interpretation, manuscript drafting and revision, finalapproval of the version to be published. ET: data analysis and interpretation,manuscript drafting and revision, final approval of the version to bepublished. AL: data analysis and interpretation, manuscript drafting andrevision, final approval of the version to be published. SM: data analysis andinterpretation, manuscript drafting and revision, final approval of the versionto be published. GDM: data analysis and interpretation, manuscript draftingand revision, final approval of the version to be published. All authors readand approved the final manuscript.Received: 11 May 2013 Accepted: 29 May 2013Published: 10 June 2013References1. Engstrom M, Hagen K, Bjork MH, Stovner LJ, Gravdahl GB, Stjern M, Sand T(2013) Sleep quality, arousal and pain thresholds in migraineurs: a blindedcontrolled polysomnographic study. The journal of headache and pain 14(1):12. doi:10.1186/1129-2377-14-122. Onen SH, Alloui A, Gross A, Eschallier A, Dubray C (2001) The effects of totalsleep deprivation, selective sleep interruption and sleep recovery on paintolerance thresholds in healthy subjects. J Sleep Res 10(1):35–423. Andress-Rothrock D, King W, Rothrock J (2010) An analysis of migrainetriggers in a clinic-based population. Headache 50(8):1366–1370.doi:10.1111/j.1526-4610.2010.01753.x4. Smith MT, Edwards RR, McCann UD, Haythornthwaite JA (2007) The effectsof sleep deprivation on pain inhibition and spontaneous pain in women.Sleep 30(4):494–5055. Della Marca G, Vollono C, Rubino M, Di Trapani G, Mariotti P, Tonali PA(2006) Dysfunction of arousal systems in sleep-related migraine withoutaura. Cephalalgia: an international journal of headache 26(7):857–864.6. Poryazova R, Werth E, Parrino L, Terzano MG, Bassetti CL (2011) Cyclicalternating pattern in narcolepsy patients and healthy controls after partialand total sleep deprivation. Clin Neurophysiol: official journal of theInternational Federation of Clinical Neurophysiology 122(9):1788–1793.doi:10.1016/j.clinph.2011.02.0287. Borsook D, Maleki N, Becerra L, McEwen B (2012) Understanding migrainethrough the lens of maladaptive stress responses: a model disease ofallostatic load. Neuron 73(2):219–234. doi:10.1016/j.neuron.2012.01.001doi:10.1186/1129-2377-14-50Cite this article as: Vollono et al.: Migraine, arousal and sleepdeprivation: comment on: “sleep quality, arousal and pain thresholds inmigraineurs: a blinded controlled polysomnographic study”. The Journalof Headache and Pain 2013 14:50.Submit your manuscript to a journal and benefi t from:7 Convenient online submission7 Rigorous peer review7 Immediate publication on acceptance7 Open access: articles freely available online7 High visibility within the fi eld7 Retaining the copyright to your article    Submit your next manuscript at 7 springeropen.com

Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study"

Springer - Publisher Connector

Migraine, arousal and sleep deprivation: comment on: “sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study”

Abstract
          We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation, which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation. The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep, and represents part of a more general vulnerability to incoming stimuli.</jats:p

Crossref

The Journal of Headache and Pain

Vollono et al. The Journal of Headache and Pain 2013, 14:50
http://www.thejournalofheadacheandpain.com/content/14/1/50LETTER TO THE EDITOR Open AccessMigraine, arousal and sleep deprivation:
comment on: “sleep quality, arousal and pain
thresholds in migraineurs: a blinded controlled
polysomnographic study”
Catello Vollono, Elisa Testani, Anna Losurdo, Salvatore Mazza and Giacomo Della Marca*Abstract
We discuss the hypothesis proposed by Engstrom and coworkers that Migraineurs have a relative sleep deprivation,
which lowers the pain threshold and predispose to attacks. Previous data indicate that Migraineurs have a
reduction of Cyclic Alternating Pattern (CAP), an essential mechanism of NREM sleep regulation which allows to
dump the effect of incoming disruptive stimuli, and to protect sleep. The modifications of CAP observed in
Migraineurs are similar to those observed in patients with impaired arousal (narcolepsy) and after sleep deprivation.
The impairment of this mechanism makes Migraineurs more vulnerable to stimuli triggering attacks during sleep,
and represents part of a more general vulnerability to incoming stimuli.
Keywords: Migraine; Sleep; Sleep deprivation; Cyclic alternating pattern; Arousal; PainSir,
We read with great interest the paper by Engstrøm et al.
(2013) “Sleep quality, arousal and pain thresholds in
migraineurs: a blinded controlled polysomnographic study”
[1]. We appreciated the methodology of the study, never-
theless we believe that the hypothesis formulated by the
Authors in their conclusion deserves further comments.
Findings
1. In their study, the Authors evaluated psychophysio-
logical measures and polisomnography (PSG) parameters
in Migraineurs and healthy volunteers; in discussing their
results, the Authors suggested the hypothesis that
Migraineurs have a relative sleep deprivation, which in
turns lowers the pain threshold and predispose to head-
ache attacks [1]. This hypothesis is theoretically conceiv-
able, since it is based on solid data coming from Migraine
and sleep literature. It is well known, in fact, that sleep
deprivation may enhance the response to pain stimuli [2];
moreover, sleep restriction is one of the most common
triggers of migraine attacks [3].* Correspondence: dellamarca@rm.unicatt.it
Institute of Neurology, Catholic University, Policlinico Universitario ‘A.
Gemelli’, Largo A. Gemelli, 8-00168, Rome, Italy
© 2013 Vollono et al.; licensee Springer. This is
Attribution License (http://creativecommons.or
in any medium, provided the original work is p2. Nevertheless, other clinical and neurophysiological ob-
servations are not in agreement with the Authors’ hypoth-
esis. In fact, some data indicate that it is sleep continuity
disturbance, rather than simple sleep restriction, that im-
pairs endogenous pain-inhibitory function and increases
spontaneous pain [4]. Moreover, it is likely that modifica-
tion of routinely sleep habits is the major trigger, since in-
creased sleep duration predisposes to Migraine attacks to
the same extent as sleep deprivation [3].
3. The results of subjective (logs) and objective (PSG)
sleep analysis reported by Engstrøm et al. (2013) [1] do not
seem to be fully consistent with their hypothesis that
‘migraineurs on the average suffer from a relative sleep
deprivation and need more sleep than healthy controls’. In
fact, in their paper, Migraineurs showed an average total
sleep time slightly longer than controls, even though no sta-
tistically significant differences were observed between
Migraineurs and Controls in sleep macrostructure. Even
the analysis of the sleep logs does not support the
deprivation hypothesis, since Migraineurs and controls had
similar average sleep time.
4. Conversely, the Authors observed in Migraineurs a de-
crease of fast arousal index, associated with an increase of
awakenings. This finding, apparently contradictory, isan Open Access article distributed under the terms of the Creative Commons
g/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction
roperly cited.
Vollono et al. The Journal of Headache and Pain 2013, 14:50 Page 2 of 2
http://www.thejournalofheadacheandpain.com/content/14/1/50similar to that reported in a previous study of our group
[5]. In that paper [5] we studied a selected population of
sleep-related Migraineurs and we observed a reduction of
the Cyclic Alternating Pattern (CAP). Therefore, we sug-
gested that the slow-frequency, high-amplitude arousal fluc-
tuations described in the CAP model are also essential to
dump the effect of incoming disruptive stimuli, and to pro-
tect sleep from external perturbations. The impairment of
this mechanism makes Migraineurs more vulnerable to
stimuli triggering attacks during sleep.
Discussion: alternative hypothesis
On the other hand, CAP modifications similar to those de-
scribed in Migraineurs have been reported in normal sub-
jects following sleep deprivation. Poryazova et al. (2011) [6]
investigated the regulation NREM sleep in normal subject
and narcolepsy / cataplexy patients before and after sleep
deprivation. This study [6] demonstrated that: 1) patients
with impaired arousability (narcolepsy patients) have lower
CAP rate that controls; and 2) sleep deprivation induces a
reduction of CAP rate, which, in normal subjects after
deprivation, reached values similar to those reported in our
study for Migraineurs.
Whatever the interpretation, we believe that these data,
taken together, suggest that Migraine is a condition in
which an impairment of arousal responses occurs. As sug-
gested by Borsook et al. (2012), Migraine is associated with
alterations in normal homeostatic mechanisms (e.g., altered
sleep, abnormal autonomic function). When stressors be-
come frequent and/or severe, allostatic responses may be
dysregulated and become maladaptive (“allostatic load”).
Such allostatic load, in turn, may alter brain responses to
stressors; therefore, behavior and systemic physiology are
altered in ways that can, in a vicious cycle, lead to further
allostatic load [7]. In this sense, arousals during sleep must
be considered as an homeostatic, adaptive response, rather
than a ‘pathologic’, disruptive phenomenon, which can be
detrimental for sleep. The impaired arousability during
sleep, seen in this view, is part of a more general decreased
ability of Migraineurs to process incoming stimuli.
Abbreviations
CAP: Cyclic alternating pattern; NREM: Non rapid eye movement;
PSG: Polysomnography.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CV: data analysis and interpretation, manuscript drafting and revision, final
approval of the version to be published. ET: data analysis and interpretation,
manuscript drafting and revision, final approval of the version to be
published. AL: data analysis and interpretation, manuscript drafting and
revision, final approval of the version to be published. SM: data analysis and
interpretation, manuscript drafting and revision, final approval of the version
to be published. GDM: data analysis and interpretation, manuscript drafting
and revision, final approval of the version to be published. All authors read
and approved the final manuscript.Received: 11 May 2013 Accepted: 29 May 2013
Published: 10 June 2013
References
1. Engstrom M, Hagen K, Bjork MH, Stovner LJ, Gravdahl GB, Stjern M, Sand T
(2013) Sleep quality, arousal and pain thresholds in migraineurs: a blinded
controlled polysomnographic study. The journal of headache and pain 14
(1):12. doi:10.1186/1129-2377-14-12
2. Onen SH, Alloui A, Gross A, Eschallier A, Dubray C (2001) The effects of total
sleep deprivation, selective sleep interruption and sleep recovery on pain
tolerance thresholds in healthy subjects. J Sleep Res 10(1):35–42
3. Andress-Rothrock D, King W, Rothrock J (2010) An analysis of migraine
triggers in a clinic-based population. Headache 50(8):1366–1370.
doi:10.1111/j.1526-4610.2010.01753.x
4. Smith MT, Edwards RR, McCann UD, Haythornthwaite JA (2007) The effects
of sleep deprivation on pain inhibition and spontaneous pain in women.
Sleep 30(4):494–505
5. Della Marca G, Vollono C, Rubino M, Di Trapani G, Mariotti P, Tonali PA
(2006) Dysfunction of arousal systems in sleep-related migraine without
aura. Cephalalgia: an international journal of headache 26(7):857–864.
6. Poryazova R, Werth E, Parrino L, Terzano MG, Bassetti CL (2011) Cyclic
alternating pattern in narcolepsy patients and healthy controls after partial
and total sleep deprivation. Clin Neurophysiol: official journal of the
International Federation of Clinical Neurophysiology 122(9):1788–1793.
doi:10.1016/j.clinph.2011.02.028
7. Borsook D, Maleki N, Becerra L, McEwen B (2012) Understanding migraine
through the lens of maladaptive stress responses: a model disease of
allostatic load. Neuron 73(2):219–234. doi:10.1016/j.neuron.2012.01.001
doi:10.1186/1129-2377-14-50
Cite this article as: Vollono et al.: Migraine, arousal and sleep
deprivation: comment on: “sleep quality, arousal and pain thresholds in
migraineurs: a blinded controlled polysomnographic study”. The Journal
of Headache and Pain 2013 14:50.Submit your manuscript to a 
journal and beneﬁ t from:
7 Convenient online submission
7 Rigorous peer review
7 Immediate publication on acceptance
7 Open access: articles freely available online
7 High visibility within the ﬁ eld
7 Retaining the copyright to your article
    Submit your next manuscript at 7 springeropen.com


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Migraine, arousal and sleep deprivation: comment on: "sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study"

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