CAPSAICIN EFFECTS ON BLINKING

Arq Neuropsiquiatr 2005;63(3-B):745-747
CAPSAICIN EFFECTS ON BLINKING
Fidias E. Leon-Sarmiento1,2, Jaime Bayona-Prieto1, Marta E. Leon-S3
ABSTRACT - Blinking is a normal human phenomenom involving trigeminal and facial patways. To gain
understanding on the neurobiology of blinking, five normal subjects were investigated before and after a p-
plication of transdermal capsaicin at the forehead for two weeks. No effects of topical capsaicin were de-
tected in eye blink rates. However, when capsaicin was applied to a female subject with blepharospasm, s h e
showed a dramatic restoration of her vision subsequent to blinking modification. Deactivation of abnor-
mal A-to-C fibers cross talks at the trigeminal-facial pathways seems to be the most likely mechanism of
such improvement.
KEY WORDS: capsaicin, visuomotor integration, C-fibers, blinking, dystonia.
Efectos de la capsaicina en el parpadeo
RESUMEN - El parpadeo es un fenómeno normal en los humanos que involucra las vías trigéminas faciales.
Con el fin de conocer un poco más la neurobiología de este fenómeno estudiamos cinco individuos norm a-
les antes y después de aplicar capsaicina trasdérmica en la frente de cada uno de ellos, por dos semanas.
La frecuencia de parpadeo no se alteró con la aplicación de capsaicina tópica. Sin embargo, cuando la mis-
ma sustancia se aplicó a una paciente con blefaroespasmo hubo dramática restauración de su visión, la
cual fue secundaria a la modificación de la actividad muscular palpebral. La desactivación del cruce patológi-
co de información que pasa de las fibras A a las fibras C, pertenecientes a las vías trigémino-faciales, pare c e
ser el mecanismo de acción relacionado con la aplicación de capsaicina, el que estaría directamente re l a c i o n a-
do con la recuperación clínica observada en la paciente con blefaroespasmo.
PALABRAS CLAVES: capsaicina, integración visuomotora, fibras C, parpadeo, distonía.
Blinking keeps the cornea with moisture conti-
tive (R2) and ultra-nociceptive (R3) responses of
n u o u s l y1 and reflects activity of dopaminergic sys-
the blink reflex6,7.
t e m2. In normal adult people, spontaneous eye
Several interventions have been tried in blepha-
blinking occurs 10 to 20 times per minute in a re l a-
rospasm with varying success including a recent re-
xed state without gender diff e re n c e s1 , 2. Diff e re n t
p o rt on the use of nicotine in one patient with su-
psychological conditions, psychophysics factors as
ch neurological disord e r8. Nicotine modifies sup r a s-
well as some disorders may decrease or increase b l i n-
pinal sensory-motor integration and the ultranoci-
king such as focal dystonia. Blepharospasm, a form
ceptive response (R3) of the electrically elicited b l i n k
of focal dystonia, characterized by repetitive invol-
reflex in a similar way as topical capsaicin and the
u n t a ry sustained contractions of the orbiculari oculi
like does9 - 1 1. These neurobiological similarities
muscles, results in episodic eye closure and typical
p rompted us to know the effects, if any, of trans-
blinking changes.
d e rmal capsaicin on blinking in normal or aff e c t e d
B l e p h a ro s p a s m ’s etiology is unknown. Some re-
people with focal dystonia (e.g., blepharo s p a s m ) ,
p o rts have pointed out the possibility that noxious
which might give us more clues to understand su-
repeated aff e rent inputs produce input-output i m-
praspinal sensory-motor processing in humans.
balance of eye movements mediated by alpha and
gamma motoneuro n s3 - 5. Recent neuro p h y s i o l o g i c
METHOD
studies also suggested that such imbalance might
Five subjects (3 female, 2 male; mean age 51. 6 ± 2.3)
be due to an aff e rent A to C fibers misconnection
with intact supraspinal sensory-motor integration gave
at supraspinal levels re c o rded as abnormal nocicep-
written consent and participated in this study. None of
1G rupo Neuro.net - Instituto de Neurología Clínica y Funcional, Neurociencias Aplicadas & Neurobiología Humana, Facultad de
Salud, Universidad de Pamplona, Pamplona, Colombia; 2P rofesor de Neurología Clínica y Fisiología, UIS (1996-2000), Bucaramanga,
Colombia; 3División de Farmacoeconomía, INRI del Oriente, Bucaramanga, Colombia.
Received 27 January 2005, received in final form 22 April 2005. Accepted 23 May 2005.
Dr. Fidias E. Leon-Sarmiento, MD, PhD - Unidad de Trastornos del Movimiento y Neuromagnetismo, Neuro.net, Calle 74 No. 15-15
(201), Bogota Colombia. E-mail: feleoness@yahoo.com

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746
Arq Neuropsiquiatr 2005;63(3-B)
them received economical compensation for being part
RESULTS
of this investigation. Capsaicin patches were worn over
The blink rate in normal people was 17 ± 3 be-
the forehead from 6 pm to 6 am daily for two weeks.
f o re intervention vs 15 ± 5 after application of to-
Eye blink rate was determined in closed room noise-iso-
pical capsaicin; thus, there was no significant modi-
lated; the subjects were sat in comfortable position and
fication on eye blinking in normal volunteers re c e i-
relaxed as much as possible, they were instructed not
ving capsaicin patches during 12 hours daily for t w o
to talk during the measurement and keeping the eyes
weeks. However, transdermal capsaicin pro d u c e d
open. The measurements were taken while they were l o-
in the subject with blepharospasm gradual impro-
oking a white wall for a 5 min-period as described else-
w h e re1. Blinking was measured before and at 3, 6, 9 and
vement of clinical symptoms reaching almost com-
12 hours after capsaicin application every day for two
plete restoration of vision at the end of six-mon-
weeks. The mean of the total blinking obtained before
ths of follow-up (Table).
patch application was compared against the mean val-
ue obtained after intervention using chi square; signifi-
DISCUSSION
cant p value was set at 0.05.
Loss of nigrostriatal dopaminergic cells decre a s-
In order to know if the neurobiological results ob-
es blink rate (e.g., Parkinson disease) and hypersen-
tained from normal volunteers paralleled people’s data
sitivity of central dopamine system increases it ( e . g . ,
with some forms of supraspinal sensorimotor disintegra-
s c h i z o p h re n i a )2. There f o re, the absence of capsai-
tion such as blepharospasm, we applied capsaicin patch-
es to a 57 years old Colombian woman who had this neu-
cin effects in blinking of normal people as observ-
rological condition. Her clinical picture started one year
ed here is in line with the dopamine influence on
b e f o re consultation which was pro g ressing until lead
it in similar populations2. It should be re m e m b e re d
her to a complete dissability of dayly life activies. She
that dopamine modulates significantly the e l e c t r i-
had never received medications for her symptoms includ-
cally elicited non-nociceptive (R1) and nociceptive
ing botulinum toxin treatment. The patches were worn
(R2) blink reflex responses which have to do with
over her forehead from 6 pm to 6 am daily for two we-
spontaneous but not with forceful blinking6, 1 4.
eks, and a visual restoration scale similar to the one used
M o re important were the results observed in t h e
in previous re p o rt s8 was constructed asking the patient
patient with blepharospasm.
to read a newspaper for at least 3 minutes1 2. at every vis-
it. Since the blinking rate does not reflect the severity
In this case, capsaicin produced vision impro v e-
of blepharospasm, we applied the severity rating scale
ment astonishingly similar to that described in ano-
(SRS) before and after interv e n t i o n s1 3 to measure clini-
ther patient with blepharospasm who received ni-
cal pro g ression. At two weeks of intervention the patient
cotine spray8. However, we went further that this
described improvement in her vision subsequent to blink-
latter re p o rt in demonstrating visual function im-
ing changes reflected in the SRS. After that, we applied
p rovement because we used the three minutes
the patches every other day for another two weeks. Since
reading test9 as well as the SRS1 3 both of which de-
the patient’s vision continued improving the patches
fine severity and functional health in blepharo s-
w e re applied every third day for two weeks and, final-
pasm patients. It should be stressed that blinking
l y, every sixth day for two weeks and half during 24 hours
rate scales might not be useful to test patients with
each. The patient was followed-up for a six-month peri-
focal dystonia affecting eye muscles because, some-
od similarly as done elsewhere8.
times, the forceful eyelid contractions detected,
the less blinking rate will be registered.
Table. Percentage restoration (%) of vision after application
Capsaicin acts on C-fibers, mostly polymodal
of transdermal capsaicin in a subject with blepharospasm. 0:
nociceptors, exerting its main electro p h y s i o l o g ical
unable to read at all, 100: able to read for 3 minutes12.
e ffects on sodium and calcium conductance with a
subsequent potassium and perhaps chloride con-
Time
%
SRS13
ductance modification leading it to secondary cel-
Treatment onset
0-10
4
lular hyperpolarization1 0. These cellular changes a re
detected as modifications of the ultranociceptive
2 weeks
20-30
3
response (R3) of electrically elicited the blink re-
4 weeks
40-50
3
f l e x1 0, which is due to C-fibers activation pre s e n t s
in human trigemino-facial pathways7,9,10.
6 weeks
50
2
Recent studies also showed that capsaicin modi-
8 weeks and half
80-90
1
fies presynaptic inhibition of low threshold aff e r-
Six months follow-up
90-100
1
e n t s1 5, a mechanism involved in modulation of R2

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Arq Neuropsiquiatr 2005;63(3-B)
747
responses of the blink re f l e x1 6. If so, capsaicin would
4 . Saito S, Moller AR. Chronic electrical stimulation of the facial nerve cau-
ses signs of facial nucleus hypersensitivity. Neurol Res 1993;15:225-231.
deactivate the pathological A-to-C fibers cross talk1 7,
5. Leon-S FE, Arimura K, Chavez AM. A re-evaluation of the mechanism
originated by the repetitive noxious aff e rent stim-
of action of botulinum toxin in facial movement disorders of man. Med
Hypoth 1998;51:305-307.
uli on trigeminal nerves well known to occur in ble-
6. Leon-S FE, Arimura K, Osame M. Three silent periods in the orbicula-
p h a rospasm, with further plastic changes in the
ri oculi reflex of man: normal findings and some clinical vignettes. Elec-
tromyogr Clin Neurophysiol 2001;41:393-400.
central sensori-motor program involving the so-
7. Leon-Sarmiento FE, Bayona-Prieto J, Gomez J. Neurophysiology of ble-
called blinking generator1 8, leading to produce the
p h a rospasm and multiple system atrophy: clues to its pathophysiolo-
gy. Parkinson Rel Dis 2005;11:199-201.
vision improvement of our patient as shown here.
8. Dursun SM, Hewitt S, King AL, et al. Treatment of blepharospasm with
nicotine nasal spray. Lancet 1996;348: 60
Such changes on sensory inputs might further
9. Leon-S FE, Suwazono S, Takenaga S, et al. The effects of tobacco smok-
modulate motoneuro n s ’s firing involved with the
ing on the short, middle and long latency responses of the blink re f l e x
in humans. J Clin Neurophysiol 1997;14:144-149.
supraspinal motor control of facial muscles, simila-
10. Leon-S FE, Chavez AM. Selective inhibition of ipsilateral and contralate-
rly as nicotine and botulinum toxin injection does8 -
ral R3 of the blink reflex by capsaicin. Muscle Nerve 1997;20:1606-1607.
1 1. Further investigations in bigger populations u s i n g
11 . Leon-S FE, Arimura K, Suwazono S, et al. The effects of shounousui on the
t h ree responses of the blink reflex in man. Muscle Nerve 1997;20:11 0 - 112
this neuro p h a rmacological approach along with
12. Defazio G, Lepore V, Abbruzzese G, et al. Reliability among neurolo-
s u p p o rtive neurophysiologic studies is worth of
gist in the severity assessment of blepharospasm and oro m a n d i b u l a r
dystonia: a multicenter study. Mov Dis 1994;9:616-621.
t rying to gain a better understanding on the neu-
13. Lindeboom R, De Haan R, Aramideh M, et al. The blepharospasm dis-
robiology of not only normal blinking but also sen-
ability scale: an instrument for the assessment of functional health in
blepharospasm. Mov Dis 1995;10:444-449.
sorimotor dysfunctions as suggested elsewhere8.
14. Basso MA, Strecker RE, Evinger C. Midbrain 6-hydroxydopamine le-
sions modulate blink reflex excitability. Exp Brain Res 1993;94:88-96.
15. Magerl W, Treede RD. Secondary tactile hypoesthesia: a novel type of
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