J Oral Maxillofac Surg

68:2159-2163, 2010

Clinical Evaluation of Polyvinylpyrrolidone

Sodium Hyalonurate Gel and 0.2%
Chlorhexidine Gel for Pain After Oral
Mucosa Biopsy: A Preliminary Study
Pia López-Jornet, PhD, MD, DDS,*
Fabio Camacho-Alonso, PhD, DDS,† and
Ascensión Martinez-Canovas, DDS‡
Purpose: To study the symptoms of patients during the 7 days after incisional biopsy of the oral mucosa
and the application of polyvinylpyrrolidone-sodium hyalonurate (Aloclair) gel or 0.2% chlorhexidine
digluconate gel.
Materials and Methods: A total of 90 consecutive patients with lesions requiring histopathologic
analysis were studied. These patients were divided randomly into 3 groups. Group I (control group)
received no topical treatment. For group II, the site of surgical intervention was treated topically with
polyvinylpyrrolidone sodium hyalonurate (Aloclair; Sinclair Pharma, Surrey, United Kingdom) gel 3 times
daily for 1 week. Group III was treated the same as group II but with 0.2% chorhexidine digluconate gel.
Using a visual analog scale, we determined the interval at which the postoperative pain was maximal, and
which parts of the mouth experienced the most postoperative complications.
Results: The most intense peaks of maximal pain were recorded in the control group, with the maximal
pain occurring 2 hours (median 2.2, range 0 to 8.5) after surgery, after which it tended to diminish
gradually during the week of the study period. The maximal level of pain was significantly lower in
groups II and III than in the control group (P ⫽ .048 and P ⫽ .054, respectively). The lip was the site
most likely to experience maximal pain.
Conclusion: Topical application of polyvinylpyrrolidone sodium hyalonurate and chlorhexidine diglu-
conate decreases the symptoms of oral mucosa biopsy.
© 2010 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 68:2159-2163, 2010

Oral biopsy is considered an irrefutable test for the
diagnosis of illnesses of the oral mucosa and the
subsequent planning of suitable therapeutic treat-
ment.1 Such biopsies are considered minor surgery
and are generally performed with the patient re-
ceiving local anesthetic. However, all oral surgical
procedures produce secondary effects such as pain
Received from Department of Oral Medicine, University of Murcia
Faculty of Medicine and Odontology, Murcia, Spain.
*Professor.
†Professor.
‡Dentist.
Address correspondence and reprint requests to Dr López-Jornet:
Clínica Odontológica Universitaria, Hospital Morales Meseguer,
Avda. Marqués de los Vélez s/n, Murcia 30008 Spain; e-mail:
majornet@um.es
© 2010 American Association of Oral and Maxillofacial Surgeons
0278-2391/10/6809-0020$36.00/0
doi:10.1016/j.joms.2009.09.047
and inflammation, the magnitude of which depends
on the degree of tissue damage produced.2,3 Re-
viewing the studies included in Medline, a number
of reports have been published concerning the
pain, inflammation, and trismus occurring after the
removal of teeth or after implantation and periapi-
cal surgery, periodontal treatment, or carbon diox-
ide laser surgery.4-13 However, very few studies
have considered the pain experienced by patients
after oral mucosal biopsy.1,14
Previous studies of the postoperative pain after
surgical removal of third molars found no relationship
between the operative trauma and the magnitude of
postoperative pain.15,16 However, pain could result
from other factors.8
Immediately after oral biopsy, patients might find
it difficult to perform good oral hygiene practices
because the tissue of their mouths is extremely
fragile.17 In such cases, chlorhexidine has been
considered a good prophylactic against postopera-

2159
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2160
tive infection.18,19 A bioadhesive gel containing
0.2% chlorhexidine placed over the surgical wound
has a more direct effect than mouthwashes and also
prolongs the active effect of the drug.
Recent studies have investigated whether this bar-
rier might improve the clinical signs by protecting the
mucosa from injury, insult, or trauma. The application
of Aloclair (Sinclair Pharma, Surrey, United Kingdom),
a bioadherent concentrated viscous oral gel com-
posed of polyvinylpyrrolidone, hyaluronic acid, and
glycyrrhetinic acid, has been recommended to treat
the symptoms of oral lesions of differing etiolo-
gies.20-23
Because it is often necessary to biopsy oral lesions
to obtain a definitive diagnosis, a clear understanding
of the pain and swelling associated with such proce-
dures could help clinicians to properly prepare their
patients.
The objective of the present study was to study the
effect of applying Aloclair gel and 0.2% chlorhexidine
digluconate topically to the surgical wound 3 times
daily after incisional oral mucosa biopsy on the pain
experienced by patients during the first 7 days after
biopsy.
Materials and Methods
The study was performed at the Oral Medicine
Teaching Unit of the University of Murcia Faculty of
Medicine and Dentistry from January 2007 to Decem-
ber 2008, with the approval of the local bioethics
committee. A total of 93 consecutive patients were
included. The inclusion criteria were a lesion in the
oral mucosa requiring histopathologic study for diag-
nostic purposes. Patients for whom the intervention
was not recommended and those with an allergy or
hypersensitivity to the products used were excluded.
All participants provided informed consent, accord-
ing to the Helsinki Declaration. Of the 93 patients, 3
were excluded because they did not complete the
daily log.
All 90 patients underwent incisional biopsies of the
oral mucosa. All the biopsies were performed by the
same operator with the patient under local anesthesia
(4% articaine and 1:100,000 adrenaline; Inibsa, Lliça
de Vall, Barcelona, Spain; never more than 1 capsule)
using a circular, 6-mm-diameter circular tissue punch
(Biopsy Punch de Stiefel; Laboratorios Stiefel, SA,
Pinto, Madrid, Spain). The biopsy sites were sutured
with a sterile suture (Normon 3-0; Laboratorios Nor-
mon, Madrid, Spain).
Before the intervention, the patients were ran-
domly allocated from a computer-generated list of
random numbers into 1 of 3 groups. After biopsy,
group I (control group) received no topical treat-
ment. In group II, the site of surgical intervention was
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STUDY OF PAIN AFTER ORAL BIOPSY
treated topically with polyvinylpyrrolidone sodium
hyalonurate (Aloclair) gel 3 times daily for 7 days. The
first dose was given in the immediate postoperative
period. Aloclair includes purified water, maltodextrin,
propylene glycol, polyvinypyrrolidone, hyaluronic
acid, glycyrrhetinic acid, and extract of licorice.
Group III was treated the same as group II but with
0.2% chorhexidine digluconate gel (Bexident encias
Isdin, Barcelona, Spain). After biopsy, all the patients
were prescribed 600 mg of ibuprofen to be taken
every 8 hours for 4 days.
To evaluate the pain intensity, a visual analog scale
(VAS) was used. This VAS consisted of a 100-mm
horizontal line anchored at one end with the words
“no pain” and at the other end with the words “worst
pain imaginable.” Each patient was instructed how to
use the scale and asked to mark the intensity of pain
at 2, 4, 6, 12, and 24 hours after biopsy, and daily for
the next 6 days. The measurements were recorded by
the patient at home at 12:00 PM. The patients were
examined 24 hours and 7 days after biopsy. Records
were kept of patient age, gender, and biopsy site.
STATISTICAL ANALYSIS
The data were analyzed using the Statistical Pack-
age for Social Sciences, version 12.0, statistical pro-
gram (SPSS, Chicago, IL). A descriptive study was
done of each variable. The Kolmogorov-Smirnov nor-
mality test and Levene variance homogeneity test
were applied. The data with a skewed distribution
were analyzed using a nonparametric ranking test.
The associations between the different qualitative
variables were studied using Pearson’s ␹2 test. The
Kruskal-Wallis test (for more than 2 samples) and
the Mann-Whitney U test for 2 independent samples
were used for quantitative variables. A probability of
P ⱕ .05 was accepted as significant.
Results
The mean age of the 90 patients was 52.1 ⫾ 13.4
years (range 20 to 78), and 24 were men (26.7%) and
66 (73.33%) were women (Table 1).
The biopsy sites were the lip in 23 (25.6%), cheek
mucosa in 43 (47.8%), alveolar mucosa or gum in 14
(15.6%), hard palate in 5 (5.6%), and lingual mucosa in
5 (5.6%).
The maximal pain value was recorded by the control
group, with the maximal pain recorded 2 hours (median
2.2, range 0 to 8.5) after biopsy, after which it dimin-
ished gradually as the week progressed (Table 2).
The site of maximal pain was the lip, which had the
greatest median score (Table 3). The application of
Aloclair gel (3 times daily) and 0.2% chlorhexidine
digluconate (3 times daily) had no adverse effect and
was well accepted by all patients.
LÓPEZ-JORNET ET AL 2161

Table 1. PATIENT CHARACTERISTICS

Control Group PSH Group Chlorhexidine Group

Characteristic (n ⫽ 30) (n ⫽ 30) (n ⫽ 30) P Value

Age (yr) .328

Median 51.5 56.0 57.5
Range 20-71 31-78 20-75
Gender (n) .303
Male 6 (20) 7 (23.3) 11 (36.7)
Female 24 (80) 23 (76.7) 19 (63.3)
Site (n) ⬍.001
Lip 14 (46.7) 6 (20.0) 3 (10.0)
Cheek mucosa 6 (20.0) 18 (60.0) 19 (63.3)
Gums 5 (16.7) 4 (13.3) 5 (16.7)
Palate 5 (16.7) 0 (0) 0 (0)
Tongue 0 (0) 2 (6.7) 3 (10.0)
Abbreviation: PSH, polyvinylpyrrolidone sodium hyaluronate gel.
Data in parentheses are percentages.
*Kruskal-Wallis and Pearson’s ␹2 tests.
López-Jornet et al. Study of Pain After Oral Biopsy. J Oral Maxillofac Surg 2010.

Discussion they are experiencing, or have experienced, pain.25

The present study used the subjective evaluation of
postoperative pain as recorded by the patients using a
VAS after incisional biopsy of the oral mucosa and
application of Aloclair gel and 0.2% chlorhexidine
digluconate. Both drugs diminished the pain com-
pared with the control group.
In the case of pain, a subjective sensation, no sys-
tem can really be used to measure it,8 and any varia-
tions in the response to painful stimuli depend on
personal, cultural, and social factors. However, a
number of indirect ways are available for measuring
the pain experience. One simple, but imprecise,
method is to measure the dose of analgesics required
to obtain a subjective reduction in pain of “more than
one half” in individual subjects.24 Another simple
method of low sensitivity is to ask patients whether
More sensitive methods include the McGrill Pain
Questionnaire,26 which has been shown to be a sen-
sitive method of recording both the type and the
intensity of pain. However, the use of the McGrill Pain
Questionnaire is dependent on patients understand-
ing the many verbal descriptions of pain. In our study,
we believed its repeated use for 7 consecutive days
would be too complex for many of our patients.
The VAS is a simple method of self-rating subjec-
tive sensations, including pain. The use of quanti-
tative or VASs is widely considered a valid method
of measuring pain.2,25 VASs have been used to study
pain related to teeth,11,14 pain and inflammation
after the extraction of third mandibular molars,1-3,15
and to measure the pain experience of patients
with wounds healing after oral mucosal biopsy.1,14

Table 2. INCIDENCE AND SEVERITY OF PAIN DURING 7 DAYS AFTER BIOPSY OF ORAL MUCOSA

Interval After Biopsy Control Group PSH Group Chlorhexidine Group P Value*

2 hr 2.2 (0-8.5) 0.3 (0-10.0) 1.5 (0-7.0) .048

6 hr 1.6 (0-8.0) 0.6 (0-10.0) 2.0 (0-8.0) .569
12 hr 2.0 (0-9.5) 0.6 (0-10.0) 0.8 (0-8.0) .216
1d 2.0 (0-9.0) 0.8 (0-10.0) 0.9 (0-7.0) .099
2d 0.7 (0-7.0) 0.2 (0-7.5) 0.2 (0-7.0) .670
3d 0.4 (0-8.0) 0 (0-9.2) 0 (0-6.0) .375
4d 0.2 (0-8.0) 0 (0-6.0) 0 (0-5.0) .575
5d 0 (0-9.0) 0 (0-5.0) 0 (0-5.0) .975
6d 0 (0-10.0) 0 (0-5.0) 0 (0-4.6) 913
7d 0 (0-4.0) 0 (0-5.0) 0 (0-2.9) .878
Abbreviation: PSH, polyvinylpyrrolidone sodium hyaluronate gel.
Data presented as median, with range in parentheses.
*Kruskal-Wallis test.
López-Jornet et al. Study of Pain After Oral Biopsy. J Oral Maxillofac Surg 2010.

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2162 STUDY OF PAIN AFTER ORAL BIOPSY

Table 3. COMPARISON OF MEDIAN PAIN SCORES (RECORDED AT PEAK PAIN INTENSITY 2 HOURS AFTER BIOPSY)
STRATIFIED BY INTRAORAL BIOPSY SITE AND STUDY GROUPS

Site Control Group PSH Group Chlorhexidine Group P Value

Lip (n ⫽ 23) .084

Patients (n) 14 6 3
Median pain score 2.5 0.2 1.0
Range 0-8.5 0-5.0 0-7.0
Cheek mucosa (n ⫽ 43) .714
Patients (n) 6 18 19
Median pain score 0.7 0.3 2.0
Range 0-4.5 0-10.0 0-7.0
Gums (n ⫽ 14) .125
Patients (n) 5 4 5
Median pain score 1.7 0 2.0
Range 1.0-8.0 0-1.6 0-5.0
Palate (n ⫽ 5) —
Patients (n) 5 0 0
Median pain score 2.0
Range 0.7-5.0
Tongue (n ⫽ 5) .213
Patients (n) 0 2 3
Median pain score 1.0 0
Range 0-6.0 0-2.0
Abbreviation: PSH, polyvinylpyrrolidone sodium hyaluronate gel.
*Kruskal-Wallis test and Mann-Whitney U test.
López-Jornet et al. Study of Pain After Oral Biopsy. J Oral Maxillofac Surg 2010.

However, no studies have considered pain after oral
biopsy and the application of products such as
Aloclair or 0.2% chlorhexidine digluconate.
Of the antiseptics available, chlorhexidine has
shown itself to be a good prophylactic against oral
infection. However, antibiotics have a high cost be-
cause they tend to produce resistance, limiting their
use. In the group using 2% chlorhexidine digluconate,
the response to pain was less than that in the control
group, perhaps because its direct application to the
target tissue in close contact with the surgical wound,
together with its prolonged release, formed a barrier
against infectious complications.18,19,26,27
According to most investigators, the postoperative
pain associated with the extraction of third mandib-
ular molars usually begins just after the effects of
the anesthetic wears off and is maximum during the
first day. van der Westhuijzen et al7 found that the
pain peaked about 1 hour after surgery. Chiu and
Cheung28 and Sanchis et al29 reported that the pain
peaked at 6 hours. In our study, all the biopsies were
performed with perilesional anesthesia, never a trun-
cal block; thus, the effect disappeared rapidly, en-
couraging the appearance of pain after a short interval
(2 hours). Regarding its evolution, Kearns et al1 found
the pain after oral biopsy had reduced quite consid-
erably from the third day onward.
The use of Gelclair (marketed in Spain as Aloclair)
has previously been studied for the treatment of oral
mucositis caused by chemotherapy or radiotherapy. It
forms a protective layer over the oral mucosa that
soothes the irritated tissues and reduces pain. The
main ingredients in Aloclair include purified water,
maltodextrin, propylene glycol, polyvinylpyrrolidone
(a hydrophilic polymer that acts as a muco-adherent
and film-forming agent, which enhances tissue hydra-
tion and has been shown to accelerate wound healing
in animal models and human wounds), hyaluronic
acid (sodium hyaluronate—a viscous fluid that occurs
naturally in the body and promotes healing by hydrat-
ing the mucus membranes and acting as a protective
film-forming, coating substance), and glycyrrhetinic
acid, a licorice extract that mediates healing through
its anti-inflammatory properties as a cyclo-oxygenase
inhibitor.20-23
The pain “scores” registered during the week after
biopsy of the oral mucosa never exceeded 2.5 on a
scale of 0 to 10. Biopsy is an essential tool for estab-
lishing the correct diagnosis and applying the most
suitable treatment. The scores registered in our study
were lower than those in the groups in whom the 2
products were applied.
The limitations of our study should be considered,
because this was an open study using a quality-of-life
index. The results of our study would have been
improved by using a placebo arm in the control
group. The data must be considered as preliminary
and orienting. New data are needed to give a better
understanding of the efficacy of, and the indications
for, Aloclair and chlorhexidine and their possible in-

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LÓPEZ-JORNET ET AL
clusion in therapy protocols. However, both seem to
provide an effective barrier mechanism that improves
the postoperative experience of patients.
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