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ACTA OPHTHALMOLOGICA SCANDINAVICA 2004

Acupuncture treatment in
patients with keratoconjunctivitis
sicca: a pilot study
Marita Andersson Grönlund,1 Ulf Stenevi1 and Thomas
Lundeberg2
1
Institute of Clinical Neuroscience, Section of Ophthalmology, Sahlgrenska Academy
at Gothenburg University, Gothenburg, Sweden
2
Department of Physiology II, Karolinska Institute, Stockholm, Sweden

ABSTRACT.
Aim: To evaluate the effects of acupuncture in patients with keratoconjunctivitis dry eye tests such as: tear break-up
sicca (KCS). time (BUT), indicating tear quality; the
Material and Methods: Twenty-five patients (20 women, five men) with KCS Schirmer-1 test (S1T), indicating tear
were randomly assigned to an acupuncture treatment group or a control group. production, and Rose-Bengal staining
The effects of acupuncture were evaluated by a questionnaire on symptoms, visual (RBS), indicating ocular surface disease
analogue scale recordings, registration of drop frequency, and dry eye tests. Ten (Paschides et al. 1989; Prause 1989;
acupuncture sessions were given. Follow-up was carried out after 2–3 weeks Klaassen-Broekema et al. 1992).
and again after a mean period of 8 months. Sjögren’s syndrome is an auto-
Results: Patients receiving acupuncture felt better at the first follow-up com- immune disease of unknown origin,
characterized by lymphocyte infiltra-
pared with the control group (p ¼ 0.036). However, no statistical significance
tion of exocrine glands and occurrence
could be found concerning any change, or difference, in the total number of
of auto-antibodies such as rheumatoid
subjective symptoms, dosage frequency or, as indicated by the dry eye tests, factor (RF), antinuclear antibodies
tear quality, tear secretion and ocular surface disease. (ANA), and SS-A and SS-B antibodies.
Conclusion: The results indicate that acupuncture has subjective beneficial The term ‘primary SS’ is used when the
effects in patients with KCS and could therefore be tried as a complement to simultaneous presence of xerostomia
ordinary treatment. and KCS are found. ‘Secondary SS’
is defined as KCS and/or xerostomia in
Key words: acupuncture – dry eye – keratoconjunctivitis sicca (KCS) – sensory nerve stimulation – association with another chronic inflam-
Sjögren’s syndrome (SS) matory connective tissue disease (e.g.
rheumatoid arthritis (RA), systemic
Acta Ophthalmol. Scand. 2004: 82: 283–290 lupus erythematosus (SLE), scleroderma
Copyright # Acta Ophthalmol Scand 2004. or polymyositis) (Manthorpe et al. 1986;
Kroneld et al. 1997). Worldwide, several
doi: 10.1111/j.1600-0420.2004.00254.x different systems of classification criteria
for SS are in use (Fox & Saito 1994;
Vitali et al. 1996).
deficiency dry eye (TDDE) and evap- The conventional treatment for KCS
Introduction orative dry eye (EDE). Tear deficiency today is symptomatic. Replacement
Keratoconjunctivitis sicca (KCS), the dry eye is again sub-divided into therapy consists of lubricating oint-
symptoms of which include foreign Sjögren’s syndrome (SS) tear deficiency, ments, ocular inserts and different
body sensation, burning, itching, red- which is immune, and non-Sjögren’s tear types of artificial tear drops with differ-
ness, photophobia and blurred vision, deficiency, which is non-immune (Lemp ent degrees of viscosity, ocular surface
can be caused by various diseases and 1995). Decreased tear production, affinity, and tonicity and toxicity levels
by disorders of the eye and eye-related decreased tear quality and damage to (Adams et al. 1992; Friedlaender 1992;
conditions (Lemp 1995). Keratocon- the ocular surface are seen in patients Grene et al. 1992; van Bijsterveld & van
junctivitis sicca, or dry eye, may be with KCS. Diagnosis is established by Hemel 1992; Ubels et al. 1995; Marner
divided into two major classes: tear history and clinical findings, including et al. 1996). Anti-inflammatory therapy

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ACTA OPHTHALMOLOGICA SCANDINAVICA 2004

(Laibovitz et al. 1993; Marsh & (1) A validated questionnaire based any time during the year prior to the
Pflugfelder 1999; Sall et al. 2000), reti- upon Workshop’s achievements (1989) beginning of this study were excluded.
noid ointment (Gilbard et al. 1989), tear and the results of the European Each patient in the acupuncture treat-
stimulants (bromhexine) and adhesive multicentre study by Vitali et al. (1993), ment group received 10 acupuncture
glycoproteins such as topical fibronectin dealing with subjective symptoms such sessions of 30 minutes each, once to
(Nelson et al. 1992) have been tried with as dryness (>3 months), foreign body twice per week. The needles were placed
varying results. The humidity of the eye sensation, burning eyes, intolerance to bilaterally at the following acupuncture
may be preserved by punctal occlusion smoke, drafts and light, redness of eyes, points selected according to traditional
(Vrabec et al. 1993; Friedlaender & Fox disturbed vision, sticky secretion and Chinese medicine (Liangyue et al. 1987):
1998; Tananuvat et al. 2001; Goto et al. increased tear flow when peeling onions. ST2, ST8, ST36, GB1, GB14, BL2 and
2003). Bandage contact lenses as well as (2) A visual analogue scale (VAS) LI4, as shown in Fig. 1. Manual
surgical procedures such as micro- recording showing the degree of stimulation was used, initially and
vascular submandibular gland transfer discomfort in the eyes translated into after 10, 20 and 30 minutes. All patients
(Macleod et al. 1990; Kumar et al. 1991) ‘better’, ‘no change’ or ‘worse’. were treated by the same doctor/
and autologous serum drops combined (3) The dosage frequency of any tear acupuncturist (MAG). Possible side-
with or without corneal epithelial substitute used. effects were registered.
stem-cell transplantation to treat severe (4) Dry eye tests, for evaluating tear The dry eye tests were also per-
dry eyes (Tsubota et al. 1996; Tai et al. quality, tear production (quantity) and formed before and after acupuncture
2002) have also been tried. Unfortu- ocular surface, performed in the follow- sessions 2 and 8. Follow-up was carried
nately, many of these treatments of ing order, according to Workshop’s out 2–3 weeks after completing the
KCS are not sufficiently effective in all achievements (1989): after installing acupuncture treatment (follow-up 1)
patients and give only short-term relief. 2.5 ml of 1% fluorescein, the tear film and again after a mean period of
In SS patients treated for xerostomia stability (i.e. the BUT) was measured 8 months (range 3–12 months) (follow-
with acupuncture Blom et al. (1992) by examining the patient with a slit- up 2). The control group underwent the
found some positive subjective results lamp using cobalt blue light. The BUT same examinations over a correspond-
regarding eye symptoms; however, the is defined as the time (in seconds) after ing period of time. Figure 2 shows a
effects were not measured qualitatively a complete blink for dry spots to flow chart of the study design.
or quantitatively. The aim of the pre- become visible on the cornea. A mean The study was approved by the
sent study was to evaluate objective of three measurements of each eye was ethical committee at the University of
and subjective effects of sensory nerve recorded (cut-off value 10 seconds). Gothenburg. Informed consent was
stimulation (acupuncture) in patients The S1T, measuring tear production obtained from the patients participat-
with KCS. over a period of 5 minutes, was per- ing in the study.
formed without local anaesthesia and
with the eyes closed. Finally, after Statistical analyses
instilling 2.5 ml of 1% Rose-Bengal Fisher’s exact test and repeated
Material and Methods solution, staining devitalized cells, measures analysis of variance (ANOVA)
A prospective, randomized study was RBS was recorded according to a for testing hypotheses between groups
performed to compare patients with method described by van Bijsterveld as well as between-subject effects
KCS undergoing acupuncture treatment (1969). A maximum total score of 9 and within-subject effects were used
as a complement to ordinary artificial was given, with 1–3 points for each of for statistical analyses. Test results
tear drops with patients receiving tear three sections of the eye: the cornea, were considered to be significant if
substitutes only. Twenty-five patients and the lateral and nasal parts of the p < 0.05.
with KCS, 20 women and five men, bulbar conjunctiva.
aged between 31 and 79 years (mean
56 years), were included in the study. Visual acuity (VA) tests, slit-lamp
The patients were randomly assigned examination and ophthalmoscopy were
Results
to an acupuncture treatment group also performed. According to the In the acupuncture group two patients
(n ¼ 12) or a control group (n ¼ 13). Copenhagen criteria (Manthorpe et al. were discontinued from the study for
Medical history and medication 1986), KCS was diagnosed when at least reasons unrelated to the acupuncture
intake were recorded, as were pre- two of the following criteria were met: treatment. In the control group one
viously performed measurements of BUT  10 seconds; S1T  10 mm/5 min- patient did not fulfil the criteria for
unstimulated salivary flow and salivary utes, or RBS  4. These criteria were the diagnosis of KCS at the initial
gland biopsy results. Unstimulated generally used for the diagnosis of examination, one patient did not attend
whole sialometry 1.5 ml/15 minutes KCS in Sweden when this study began. the follow-up examination and one
was considered abnormal and lower Before starting the acupuncture patient dropped out of the study
lip biopsy showing focal sialoadenitis treatment, the patients were informed because of intolerance to the dry eye
with a focus score of lymphoplasmo- about the possibility of any side-effects, tests. Table 1 shows the composition
cytic infiltrates >1 was regarded as such as tiredness, drowsiness, a fall in of the acupuncture treatment group
positive for SS. The subjective and blood pressure of short duration and and the control group in terms of sex,
objective effects were evaluated by a haemorrhage at the place of insertion mean age, KCS classification, and
detailed ophthalmological examination of the needles. Patients who had results of previously performed meas-
and included the following: received acupuncture for any reason at urements of unstimulated salivary flow

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Fig. 1. Location of the acupuncture points used in the study. ST2 (Sibai): in the depression at the infra-orbital foramen. With the patient looking
straight ahead, the pupil and ST2 are on the same vertical line. ST8 (Touwei): 3.5 cun (five fingers) above the supra-orbital ridge, 4.5 cun (six fingers)
lateral to the middle line. The point is located in the sulcus coronalis at the upper border of the media temporalis. ST36 (Zusanli): 3 cun (four fingers)
below the apex patellae, one finger’s width lateral to the crista anterior tibiae. GB1 (Tongziliao): lateral to the outer canthus, in the depression on the
lateral side of the orbit. GB14 (Yangbai): 1 cun (one thumb’s width) above the supra-orbital ridge. With the patient looking straight ahead GB14, ST2
and the pupil are on the same vertical line. BL2 (Zanzhu): at the nasal end of the eyebrow, on the supra-orbital notch. LI4 (Hegu): between the first
and second metacarpal bones, approximately in the middle of the second metacarpal bone on the radial side, on the highest point of margo interosseus
dorsalis when the thumb is adducted. The needles were placed bilaterally.

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ACTA OPHTHALMOLOGICA SCANDINAVICA 2004

KCS
(n=25)

Acupuncture treatment group Control group


(n=12) (n=13)

Drop-out Ophthalmologic examination Drop-out Ophthalmologic examination


n=1 n=1

Acupuncture 1 Ophthalmologic examination


Follow-up I

Dry eye tests


Drop-out
n=1

Acupuncture 2
Ophthalmologic examination
Follow-up II
Dry eye tests
(n=10)

Drop-out Acupuncture 3
n=1

Acpuncture 4

Acupuncture 5

Acupuncture 6

Acupuncture 7

Dry eye tests

Acupuncture 8

Dry eye tests

Acupuncture 9

Acupuncture 10

2 to 3 weeks

Ophthalmologic examination
Follow-up I

Mean 8 months

Ophthalmologic examination
Follow-up II
(n=10)

Fig. 2. Flow chart showing study design for 25 KCS patients randomly assigned to an acupuncture treatment group or to a control group.

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Table 1. Composition of the study population with KCS who completed the study in the treatment group noted that they had felt
acupuncture treatment group and the control group, with regard to sex, mean age, classification of better for about 4 months after complet-
KCS, unstimulated salivary flow and salivary gland biopsy results. ing the acupuncture treatment but that
after this period the positive effect had
Characteristics Acupuncture treatment Control
group n ¼ 10 group n ¼ 10 declined.
The mean score of frequency of eye-
Mean age year (range) 61 (38–79) 57 (31–75) drop use at baseline and at follow-ups 1
Sex F/M 9/1 8/2 and 2 is shown in Table 4. No statistic-
KCS classification ally significant difference could be
1 SS 3 3
found between the groups.
2 SS 5 5
Dry eye not associated with SS 2 2
When evaluating the results of the
Unstimulated salivary flow dry eye tests, we compared the results
Low 7 5 for right eyes at baseline with those for
Normal 1 4 right eyes at different time-points, as
Not performed 2 1 well as between groups. Likewise,
Salivary gland biopsy results for left eyes at baseline were
SS 3 3 compared with results for left eyes at
Not SS 4 3
different time-points and between
Not performed 3 4
groups. A comparison between the
SS ¼ Sjögren’s syndrome; 1 SS ¼ primary Sjögren’s syndrome; 2 SS ¼ secondary Sjögren’s syndrome. two groups revealed that acupuncture
was no more effective than receiving a
tear substitute in increasing tear qual-
and salivary gland biopsy results in the examination only one patient in the ity, as indicated by the BUT, in increas-
two groups of patients. acupuncture treatment group reported ing tear secretion, as indicated by the
The results of the questionnaire on symptoms of red eyes, compared with S1T, or in decreasing ocular surface
subjective symptoms are presented in six patients in the control group. How- disease, as indicated by RBS. However,
Table 2. At the initial examination all ever, no statistical significance was seen the S1T showed a statistically significant
of the patients had experienced dryness in the change in the total number of positive effect for left, but not right, eyes
of the eyes for more than 3 months. subjective symptoms either within or over time (p ¼ 0.0131) (Table 4). No
The second most frequent symptom between the groups (Table 3). statistically significant change could be
was ‘foreign body sensation’ (n ¼ 16; According to the VAS recordings, six found concerning the measurements of
acupuncture group: 8; control group: 8). patients in the acupuncture treatment the dry eye tests just before and after
At the first follow-up examination group felt better after finishing the treat- acupuncture sessions 2 and 8.
only four patients in the acupuncture ment and no one felt worse. In the con- No adverse effects of the acupunc-
group reported foreign body sensation, trol group no patient felt better and two ture treatment per se were noted.
compared with nine patients in the con- patients felt worse over the same period
trol group. The symptom of red eyes of time (p ¼ 0.036) (Fig. 3). However, at
was seen in 12 patients (acupuncture follow-up 2, there was no statistic-
group: 6; control group: 6) before the ally significant difference between the
start of the study. At the first follow-up groups. Two patients in the acupuncture Discussion
Based on the patients’ subjective
Table 2. Number of patients with KCS in the acupuncture treatment group recording subjective recordings, we found that in this study
symptoms in the questionnaire, compared with controls at baseline and follow-ups 1 and 2. sensory nerve stimulation had benefi-
cial effects on patients with KCS
Subjective symptoms (Fig. 3). According to Lemp (1995),
Baseline Follow-up 1 Follow-up 2 the best way to evaluate clinical efficacy
may be to observe symptoms and func-
ATG CG ATG CG ATG CG tional lifestyle in patients with KCS by
n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 using a validated questionnaire because
n n n n n n clinical findings and subjective symp-
Dryness >3 months 10 10 10 10 10 10
toms do not always correlate with one
Foreign body sensation 8 8 4 9 6 9 another. However, it should be noted
Burning sensation 8 5 4 8 3 6 that subjective measures are more
Intolerance to smoke 7 6 4 5 7 8 susceptible to certain kinds of bias
Intolerance to drafts 6 6 4 6 5 7 (Vincent & Richardson 1986). The find-
Intolerance to light 7 7 7 8 8 7 ings in the current report differ from
Redness 6 6 1 6 3 6 those obtained in a previous study by
Disturbed vision 7 6 4 4 4 6
Nepp et al. (1998), who found acupunc-
Sticky sensation 2 6 3 4 4 6
Increased tear flow ture to have an objective effect when
when peeling onions 4 8 2 6 4 8 treating KCS, based on BUT and S1T
results as well as on dosage frequency
ATG ¼ acupuncture treatment group; CG ¼ control group. of artificial tears.

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Table 3. Mean score of frequency of eyedrop use and total number of subjective symptoms, treatment. However, any placebo effects
according to the questionnaire in the two groups at baseline and at follow-ups 1 and 2. of the manipulation per se cannot be
excluded. Moreover, Bjerrum (1996)
Mean score (range)
reported that the signs of KCS changed
Baseline Follow-up 1 Follow-up 2 from one ocular examination to another
in as many as 21% of eyes in patients
ATG CG ATG CG ATG CG with primary SS, which also confirms
n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 the difficulties in evaluating clinical
n n n n n n findings using acupuncture, particularly
Frequency of eyedrop use 2.4 2.3 3.3 3.9 1.6 3.8 in patients with KCS.
(0–10) (0–8) (0–15) (0–10) (0–5) (0–10) The participants in the present study
Total number of 6.5 6.8 4.7 6.6 5.7 7.3 were predominantly women. Their
subjective symptoms (2–10) (3–10) (2–8)* (4–9) (3–8) (3–10)* mean age was 56 years. According to
Talal (1986), primary SS occurs nearly
ATG ¼ acupuncture treatment group; CG ¼ control group; * n ¼ 9. 10 times more frequently in women
than in men. Bjerrum (1997) found
Evaluating the clinical effects of acu- (1986) have pointed out that some that KCS was most common in persons
puncture is not easy, especially in a standardization of the acupuncture aged 50–59 years but increased equally
group of patients with KCS. It is almost treatment procedures in a study is with age in men and women.
impossible to construct a double-blind desirable for research purposes. The pre- In the present study KCS was diag-
trial involving sensory nerve stimulation sent study was designed as a two-group, nosed using the Copenhagen criteria
(Vincent & Richardson 1986) and randomized, prospective study, where (Manthorpe et al. 1986), which were
cross-over studies may be inappropriate one group received a standardization of the criteria used in our clinic at the
because of possible longterm effects acupuncture treatment as a complement time the study was initiated. Bjerrum
(Lewith & Machin 1983). A single two- to their ordinary treatment of artificial (1996) suggested modifying the
group, randomized, prospective trial has drops and the other group, the control Copenhagen criteria by changing the
been proposed by Lewith & Machin group, received only their usual cut-off value of the S1T from 10 mm/
(1983) and Vincent & Richardson eyedrops without any other form of minute to 5 mm/minute, which is the
criterion used in our clinic today. If
8 we had used the modified Copenhagen
criteria at the time of diagnosis, all but
one patient (in the control group)
would have been diagnosed as KCS
7 sufferers. According to the European
Acupuncture classification of Sjögren’s syndrome
treatment (Vitali et al. 1996), the diagnosis of
6 group (n=10) KCS is based on a S1T cut-off value
of 5 mm/5 minutes and/or RBS 4
points; however, in persons over the
5 Control group age of 60 years, S1T results should not
(n=10) be considered as tear production often
decreases with age. All of our patients,
4 both in the acupuncture treatment
group and in the control group,
fulfilled the European criteria.
The innervation and regulation of the
3 cornea, lacrimal glands and meibomian
glands as well as tear secretion and the
tear film is complex (Dartt 1994, 2001;
2 Walcott et al. 1994; Nelson 1998; Müller
et al. 2003). Both hormones, such as
androgens and prolactin, and neural
1 factors, such as encephalines, neuropep-
tide Y (NPY), substance P (SP), vaso-
active intestinal polypeptide (VIP) and
0 calcitonin gene-related peptide (CGRP),
Better No Worse are involved. Although acupuncture has
been used for more than 2000 years as a
change technique for pain relief and curing dif-
Fig. 3. Results of the visual analogue scale recordings translated into ‘better’, ‘no change’ or ferent types of diseases, its mechanism
‘worse’ at the first follow-up examination comparing the acupuncture treatment group with the of action is still not entirely known. So
control group (p ¼ 0.036). far, we know that acupuncture reacts at

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Table 4. Mean score of dry eye tests in the two groups at baseline and at follow-ups 1 and 2.

Mean score (range)

Baseline Follow-up 1 Follow-up 2

ATG ATG CG CG ATG ATG CG CG ATG ATG CG CG


OD OS OD OS OD OS OD OS OD OS OD OS
n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n¼9 n¼9 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10 n ¼ 10

BUT 6.6 6.9 6.9 7.1 7.0 7.2 7.7 8.8 7.3 7.0 7.2 7.1
(3–10) (3–10) (3–10) (2–10) (4–10) (4–10) (3–10) (4–10) (4–10) (4–10) (4–10) (3–10)
S1T 5.2 6.2 6.2 3.6 6.1 6.6 4.6 4.0 6.2 7.7 6.8 5.1
(0–22) (0.5–25) (0–19) (0–10) (0–34) (0–14) (0–12) (0–10) (0–24) (1–25) (1–30) (1–22)
RBS 3.1 4.1 4.6 4.2 3.4 4.2 5.1 3.9 2.7 2.9 3.2 3.0
(2–6) (2–6) (4–6) (1–7) (2–6) (2–8) (3–8) (1–6) (0–6)* (1–8)* (2–6)* (0–8)*

ATG ¼ acupuncture treatment group; CG ¼ control group; OD ¼ right eye; OS ¼ left eye; BUT ¼ break-up time; S1T ¼ Schirmer-1 test; RBS ¼ Rose-
Bengal staining; * n ¼ 9.

local, regional (spinal cord), and general neurotransmitters, neuropeptides and the treatment of superficial corneal disease
(brain) levels (Han & Terenius 1982; anti-inflammatory components in the in keratoconjunctivitis sicca. Acta Ophthal-
Andersson 1992; Karavis 1997a, tear film under the influence of sensory mol Scand 70: 518–521.
Bjerrum KB (1996): Test and symptoms in
1997b). One possible cause of the relief nerve stimulation would be of great
keratoconjunctivitis sicca and their correl-
achieved in these patients with KCS interest, as neural factors are involved ation. Acta Ophthalmol Scand 74: 436–441.
might be a corneal pain-relieving effect in the innervation of the lacrimal glands Bjerrum KB (1997): Keratoconjunctivitis sicca
by the acupuncture treatment. Several and cornea and in the regulation of tear and primary Sjögren’s syndrome in a Danish
neuropeptides and neurotransmitters, secretion. population aged 30–60 years. Acta Ophthal-
such as SP, CGRP, norepinephrine and mol Scand 75: 281–286.
met-encephalin, function as stimulators Blom M, Dawidson I & Angmar-Månsson B
of corneal wound healing (Müller et al. (1992): The effects of acupuncture on salivary
2003). Previous reports have shown that Acknowledgements flow rates in patients with xerostomia. Oral
Surg Med Oral Pathol 73: 293–298.
acupuncture may affect the circulatory This study was supported by grants from Blom M, Lundeberg T, Dawidson I &
system (Jansen et al. 1989a, 1989b) and the Gothenburg Medical Society and the Angmar-Månsson B (1993): Effects on local
the immune system (Lundeberg et al. Medical Faculty of the University of blood flux of acupuncture stimulation used
1988, 1991; Lundeberg 1993) by acti- Gothenburg (LUA). to treat xerostomia in patients suffering
vation of the autonomic nervous system. The results of this study were presented at from Sjögren’s syndrome. J Oral Rehab 20:
the annual meeting of the Swedish Ophthal- 541–548.
Sensory nerve stimulation may give rise mology Society, in Västerås, Sweden and at Dartt DA (1994): Regulation of tear secretion.
to vasodilatation by releasing CGRP, the 100-year anniversary of Henrik Sjögren, In: Sullivan DA (ed). Lacrimal Gland, Tear
which also acts as an endogenous anti- in Jönköping, Sweden, both in 1999. Film and Dry Eye Syndromes. New York:
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been shown to induce an increase in sal- Aires of the Biostatistics Branch, Depart- Dartt DA (2001): Regulation of lacrimal gland
ivary flow and local blood flux in ment of Mathematics, Chalmers University secretion by neurotransmitters: the EGF
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with the statistical analyses, and Anna- 741–752.
Sjögren’s syndrome (Blom et al. 1992,
Karin Larsson for taking photographs. Dawidson I, Angmar-Månsson B, Blom M,
1993). The effects of sensory nerve stimu-
Theodorsson E & Lundeberg T (1998a):
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Sensory stimulation (acupuncture) increases
flow are probably related to the release the release of vasoactive intestinal poly-
of vasodilatory neuropeptides such as References peptide in the saliva of xerostomia suffers.
VIP, NPY and CGRP (Lundeberg Adams J, Wilcox MJ, Trousdale MD, Neuropeptides 32: 543–548.
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Pain 16: 111–127. efficacy and safety of cyclosporin ophthal- Email: marita.gronlund@oft.gu.se

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