Osteoarthritis and Cartilage (2001) 9, 619–624

© 2001 OsteoArthritis Research Society International 1063–4584/01/070619+06 $35.00/0

doi:10.1053/joca.2001.0461, available online at http://www.idealibrary.com on

Modulation of the inflammatory response in the rat TMJ with increasing

doses of complete Freund’s adjuvant
R. P. Harper*†, C. A. Kerins*, J. E. McIntosh*, R. Spears* and L. L. Bellinger*
Departments of *Biomedical Sciences and †Oral and Maxillofacial Surgery and Pharmacology, Baylor College
of Dentistry, a member of The Texas A&M University System Health Science Center, Dallas, Texas, 75246,
U.S.A.

Summary
Objectives: Acute inflammation stresses the physiological system, which must respond in order to reestablish homeostasis. The purpose of
this study was to determine whether bilateral temporomandibular joint (TMJ) injections of different doses of Complete Freund’s Adjuvant
(CFA) produced dose-dependent changes in biologic markers of acute inflammation. The ability to establish an animal model with varying
degrees of joint inflammation would allow evaluation of agents or conditions that could modulate the severity of the disease.
Design: The TMJs of three groups of male Sprague–Dawley rats were injected with CFA containing varying doses of Mycobacterium
tuberculosis (MT). A group of non-injected and a group of saline injected rats were used as controls. Food intake, body weights, swelling and
chromodacryorrhea were recorded daily. Interleukin-1
(IL-1
) and corticosterone levels were assayed and condylar cartilage thickness was
measured 48 h after injections.
Results: Twenty-four hours post-injection, bilateral TMJ swelling and chromodacryorrhea were significantly (P<0.05) increased following
10 g of MT and further increased with elevated MT dose. In the CFA groups food intake was attenuated (P<0.01) 24 and 48 h post-injection
and negatively correlated with dose at 24 h. Body weight was also negatively correlated with dose. TMJ retrodiscal tissues IL-1
was
increased (P<0.05) in a dose-dependent manner. CFA increased corticosterone (P<0.05), but this elevation was not dose dependent.
Condylar cartilage thickness was decreased in a dose-dependent manner.
Conclusions: These data suggest that an intermediate dose of CFA can be used to effect submaximal levels of TMJ inflammation that will
allow experimental modulation in future studies. © 2001 OsteoArthritis Research Society International
Key words: Adjuvant, Interleukin-1
, Corticosterone, Feeding behavior, Body weight.

Introduction during inflammation cross the blood–brain barrier where

Injury to the temporomandibular joint (TMJ) can cause
inflammation of the intracapsular and surrounding tissues.
The inflammatory process involves the mobilization of
defense mechanisms that are both local and systemic in
their overall effects and may include functional and
behavioral changes that affect regeneration and repair
of the tissue. Understanding of the processes related to
TMJ inflammation is limited because of the lack of an
appropriate animal model1, which can be used to establish
quantifiable biological outcomes.
Components of TMJ inflammation that can be qualita-
tively measured include swelling of the TMJ and surround-
ing tissues and the development of stress induced
chromodacryorrhea (red eye tearing).
Quantifiable measures of inflammation can include
measures of tissue inflammatory cytokines such as inter-
leukin 1-
(IL-1
)2. Also cytokines released peripherally
Received 18 August 2000; revision requested 3 December
2000; revision received 22 March 2001; accepted 7 May 2001.
Address correspondence to: Dr R. P. Harper, Department of Oral
and Maxillofacial Surgery and Pharmacology, Baylor College of
Dentistry, 3302 Gaston Avenue, Dallas, TX 75266-0677, Tel:
903-872-6685; Fax: 903-872-6218; E-mail rharper@tambcd.edu
Presented at the American Association of Oral and Maxillofacial
Surgeons 81st Annual Meeting and Scientific Session, 29
September–2 October 1999, Boston, MA.
they, along with afferent neural pain signals, release stress
hormones such as corticosterone3–5. Sarlis et al.6 and
Selgas et al.7 have shown that inducing inflammation by
subcutaneous injection of complete Freund’s adjuvant
(CFA) causes an elevation of corticosterone. Stress
hormones, such as corticosterone, and inflammatory
cytokines, such as IL-1
, function as part of the system’s
response to stress in order to maintain or reestablish
physiological homeostasis. Also a behavioral component to
TMJ pain or inflammation may include altered chewing
patterns and food intake8.
In order to establish an animal model of TMJ inflamma-
tion capable of modulation the use of a submaximal dose of
an inflammatory inducing agent, such as CFA, would be
critical. If the CFA dose is too small inflammation may not
be apparent. On the other hand, if the dose is too large the
inflammation may be so massive that it is not subject to
extrinsic modulation. What is needed is a state of inflam-
mation that through various manipulations can be made
measurably better or worse. The purpose of this study was
to determine whether different doses of CFA injected into
the TMJ of the rat produce dose-dependent changes in
acute biologic markers of TMJ inflammation such as con-
dylar cartilage thickness, soft tissue swelling, chromodacry-
orrhea, increased retrodiscal tissue IL-1
, alterations in
plasma corticosterone and changes in food intake and
body weight.

619
620
Materials and methods
Six-week-old male (150–175 g) Sprague–Dawley rats
(Harlan Industries, Houston, TX) were caged individually
with a light–dark cycle (L:D 12:12 with lights on at 0800 h)
in a temperature-controlled (23°C) room. They were given
laboratory food (Teklad 7002, Harlan Industries, Houston,
TX) and tap water ad libitum and had several days to adjust
to their new environment. Food intake, corrected for spill-
age, was measured daily and body weight was recorded at
various times. The rats were handled daily to minimize
stress during later blood collection procedures.
Corticosterone follows a diurnal pattern of secretion and
is low at the beginning of the light phase (0700 h) when rats
start their period of inactivity and is high at the beginning of
the dark phase when the rats start their activity period.
Previously we have shown that CFA injected bilaterally into
the TMJ elevated corticosterone at the beginning of the
light phase1. On the day of experimentation at 0700 h all
the rats were removed from their cages and anesthetized
with a solution of ketamine (5.2 mg/100 g body weight) and
Rompun (0.78 mg/100 body weight). This dosage is 60% of
the normal surgical dose and was used to keep anesthetic-
related stress to a minimum. The rats were divided into
five groups: Group 1, non-injected control (N=19), Group
2, 50 l saline control (N=10); Group 3, 10 g of
Mycobacterium tuberculosis (MT) in paraffin oil (Sigma, St
Louis, MO; N=10); Group 4, 25 g MT (N=12) and Group
5, 50 g MT (N=9). A 30-gage needle was used for bilateral
injection into the superior space of the TMJ. It has been
previously assessed using radio-opaque dye that the
superior joint space can hold 50–70 L of injectable fluid9.
The rats were mobile within 20 min or less after induction of
anesthesia. Food intake and body weights were recorded
daily over the next 2 days.
Twenty-four hours post-injection, the rats were rated
using a blinded protocol for swelling and chromodacr-
yorrhea. Signs for swelling and chromodacryorrhea were
graded as 0 (none), 1 (mild), 2 (moderate) and 3 (severe).
Forty-eight hours after injection, the rats were removed
from their cages at 0700 h and killed by decapitation within
20 s in order to obtain stress-free samples. Blood samples
were collected in tubes coated with EDTA and immediately
placed on ice. Plasma was separated from the blood in a
refrigerated centrifuge and then stored at −80°C. Plasma
corticosterone was determined using radioimmunoassay
kits (ICN Biomedical, Inc., Diagnostics Division, Costa
Mesa, CA) and plasma IL-1
was determined using a rat
IL-1
ELISA kit from R & D Systems, Minneapolis, MN. The
heads were placed in plastic bags and submerged in an ice
bath. On one random side the TMJ retrodiscal tissues were
removed from each rat, rapidly frozen in liquid nitrogen, and
stored at −80°C for later ELISA assay of IL-1
. A standard
Folin Lowry assay was also performed on each retrodiscal
tissue in order to determine its total protein content. IL-1

concentration was expressed as pg/mg of protein for
statistical analysis.
On the other side the TMJ was removed en bloc, placed
into 10% buffered formalin for several days, demineralized
in Redecal (StetLab Medical Products, Inc., Lewisville, TX)
for up to 24 h, and then embedded in paraffin. Sections
(6 m) from six animals in each group were cut and stained
with hematoxylin and eosin. An area midway between the
anterior and posterior aspect of the condyle was located on
mid-saggital sections of the condyles and a picture taken
with MetaMorph 3.5 Imaging System, Universal Imaging
Corporation, West Chester, PA. At this intersection a
R. P. Harper et al.: Complete Freund’s adjuvant
vertical line was made through the articular layer, zone of
proliferation, zone of maturation and zone of hypertrophy1
and the thickness of each layer was measured using
software (Optimas 6.2, Bioscan, Edwards, WA, U.S.A.).
Next a vertical line was made 75 m each side of the first
line and thickness measurements were again taken. These
three measurements were averaged for each layer prior to
statistical analysis.
Food intake, body weight, IL-1
and hormone data were
analysed by one-way and two-way analysis of variance
with or without repeated measurements. Data found to be
significant were further analysed by a Duncan’s Multiple
Range Test to determine the location of the significant
differences. Swelling and chromodacryorrhea scores were
analysed using Kruskal–Wallis one-way analysis of vari-
ance and data found significant were further analysed
using Mann–Whitney U-test.
Results
Histological sections (Fig. 1) of the CFA injected joints
demonstrated an acute inflammatory infiltrate, including the
presence of neutrophils and macrophages, within the
intracapsular tissues of the TMJ. The intensity of this
infiltrate was seen to increase with larger doses of CFA. In
the mid portion of the condyle the depth of the articular
layer, F(4,29)=0.35, n.s.; proliferative layer, F(4,29)=0.89,
n.s; and maturation layer, F(4,29)=1.34, n.s were similar in
all groups. However, in the anterior portion of the cartilage
from the 50 g rats, the maturation zone was reduced to
just two or three layers of cells. Notably, the hypertrophic
layer was significantly reduced, F(4,29)=10.21, P<0.001,
in the 25 g (P<0.05) and 50 g (P<0.05) dose groups
when compared with the 10 g, saline and non-injected
groups. The zone of hypertrophy was decreased to just two
or three layers of cells in the 50 g rat.
The analog score for swelling in the saline injected group
was the same as that of the non-injected group (Fig. 2).
The analog score for swelling was significantly (df=4,
H=48.29, P<0.01) greater in the CFA injected groups when
compared with the two control groups. The swelling score
was significantly (P<0.01) increased in the 10 g MT group
when it was compared with the two control groups. The
swelling scores were also significantly (P<0.01) greater in
the 25 and 50 g MT groups when compared with the two
control groups and importantly further increased (P<0.02)
when compared with the 10 g MT group. Magnitude of
swelling did not differ between the 25 and 50 g MT groups.
The analog score for chromodacryorrhea in the saline
injected group was the same as that of the non-injected
group (Fig. 3). The analog score for chromodacryorrhea
score was significantly (df=4, H=32.76, P<0.01) greater in
the CFA injected groups when compared with the two
control groups. The chromodacryorrhea score was signifi-
cantly (P<0.01) increased in the 10 g MT group compared
with the two control groups. The chromodacryorrhea
scores were also significantly (P<0.01) greater in the 25
and 50 g MT groups when compared to the two control
groups. The chromodacryorrhea score of the 25 g MT
group was increased (P<0.03) over the 10 g MT group
and while also increased in the 50 g MT group when
compared with the 10 g MT group significance (P<0.15)
was not reached. Magnitude of the chromodacryorrhea
score did not differ between the 25 and 50 g MT groups.
The day prior to the start of experimentation food intake
of all the groups was similar (Fig. 4). Food intake was
Osteoarthritis and Cartilage Vol. 9, No. 7 621

Fig. 1. A well defined upper and lower joint space is seen in the control non-injected rat (a) 2.5×magnification and (b) 10×magnification. In
the rat injected with 50 g of complete Freund’s adjuvant, (c) 2.5×magnification and (d) 10×magnification, there is evidence for an acute
inflammatory infiltrate within the retrodiscal tissues and in the joint spaces. There is a remarkable decrease in the hypertrophic
chondroblastic in the CFA-injected TMJ (c) and (d).

significantly [group effect, F(4,54)=54.66, P<0.001] sup-
pressed in the groups receiving CFA over the next 48 h.
Twenty-four hours after the start of experimentation the two
control groups showed a small, but significant (P<0.01),
suppression of their food intake when compared with the
day before. On the first day post-injection the food con-
sumption of the three CFA injected groups was suppressed
compared with the two control groups. On this day the food
intake of the 10 g MT group was significantly (P<0.05)
greater than the food intake of the 50 g MT group. The
intake of the 25 g MT group was intermediate to the two
other CFA injected groups. On the second day post-
injection the food intake of the three CFA injected groups
rebounded, was of a similar magnitude, but was still
significantly less than the two control groups.
The significant [group effect, F(4,51)=137.87, P<0.001]
change in body weight 24 h after the start of experi-
mentation was reflected in the food intake (Group 1,
+0.7±1.2 g; Group 2, +1.8±1.0 g; Group 3, −23.1±1.9 g;
Group 4, −28.3±1.3 g; and Group 5, −28.6±1.1 g). The
two control groups (Groups 1 and 2) gained a similar
amount of weight. The 25 and 50 g MT groups (Groups 4
and 5) lost a similar, but significant, amount of weight when
compared with Group 3 that received the 10 g MT dose
(P<0.05) and the two control groups (P<0.01).
TMJ retrodiscal tissue IL-1
concentration differed sig-
nificantly [group effect, F(4,53)=33.26, P<0.001] among
the groups (Fig. 5). The IL-1
concentration was low and
similar in the non-injected and saline injected control
groups. There was a dose-dependent increase in IL-

among the groups. Compared with both control groups the
retrodiscal tissue IL-1
concentration was significantly, and
similarly, elevated (P<0.05) in the groups receiving the 10
and 25 g MT doses and was further elevated (P<0.05) in
the group receiving the 50 g MT dose.
Plasma corticosterone was significantly and similarly
elevated [group effect, F(4,51)=3.30, P<0.02], (P<0.05)
in the three CFA injected groups when compared with
the control groups (Group 1, 14.3±0.9 ng/ml; Group 2,
12.0±0.0 ng/ml; Group 3, 27.2±6.9 ng/ml; Group 4,
39.0±1.9 ng/ml; and Group 5, 23.9±5.1 ng/ml). The IL-1

assay had a detection limit of 12 pg/ml. All the samples,
except one, i.e., 47 pg/ml, were below the assays detection
level.
Discussion
Previously, we1,9 and others10–13 have shown that injec-
tion of CFA into the superior joint space of the rat TMJ
resulted in a profound inflammatory response that can last
for up to 6 weeks. However, it was difficult to detect a
therapeutic effect of treatment, for example, with antiinflam-
matory medications because of the overwhelming magni-
tude of this inflammation. In order to test the efficacy of
622
3 30
**,c
**,b
Score
**
1
0
Group
Fig. 2. Visual analog scale score for temporomandibular
joint (TMJ) area swelling (means±standard error). Groups: NOT-
INJ=not injected (N=19; ); SALINE=bilateral TMJ injection of
saline ( ); CFA-10 g [bilateral TMJ injection of Complete
Freund’s Adjuvant (CFA) containing 10 g of Mycobacterium tuber-
culosis, N=10; ]; CFA-25 g (N=12; ); and CFA-50 g (N=9;
). Statistical significance (Kruskal–Wallis: P<0.01) was obtained.
Post hoc analysis using Mann–Whitney U-test revealed:
**=P<0.01 in comparison with NOT-INJ and SALINE groups;
c=P<0.01 in comparison with CFA-10 g group; b=P<0.02 in
comparison with CFA-10 g group.
3
**,a
**
2 **
Score
1 30
0 10
Group
Fig. 3. Visual analog scale score for chromodacryorrhea
(means±standard error). See Fig. 2 legend for group definitions.
Statistical significance (Kruskal–Wallis: P<0.01) was obtained.
Post hoc analysis using Mann–Whitney U-test revealed:
**=P<0.01 in comparison with NOT-INJ and SALINE groups;
a=P<0.05 in comparison with CFA-10 g group.
various treatment modalities including pharmacological
agents it would be more appropriate to have an animal
model capable of modulation with regard to the inflam-
matory process. Other studies14,15 using various animal
models make no comment regarding the magnitude of the
inflammation produced in their models. Therefore, the
question that was addressed in this study was whether
submaximal levels of inflammation could be produced in
the rat TMJ and if these levels were in fact dose dependent
with respect to the amount of CFA injected into the joint. In
fact, the present study demonstrates that a dose-
dependent CFA-induced inflammatory response could be
established in the TMJ of the rat. In the present study
histological sections of the CFA injected joints demon-
strated an acute inflammatory infiltrate, including the
presence of neutrophils and macrophages, within the
intracapsular tissues of the TMJ which varies with the dose
of CFA that was injected. The intensity of this infiltrate was
seen to increase with larger doses of CFA. It is interesting
to note the decrease in the thickness of the condylar
R. P. Harper et al.: Complete Freund’s adjuvant
Food intake (grams)
d d
20
** **
**
10
**
**
**,a
0
Pre-injection +1 Day +2 Day
Fig. 4. Daily food intake, in grams, on the day before injections
and for two days (+1 and +2) thereafter. See Fig. 2 legend for
group definitions. Statistical significance (ANOVA with repeated
measurements: P<0.001) was obtained. Post hoc analysis using
Duncan’s multiple range test revealed: **=P<0.01 in comparison
with NOT-INJ and SALINE groups; a=P<0.05 in comparison with
CFA-10 g group; and d=P<0.05 in comparison with, respectively,
NOT-INJ and SALINE groups.
60
**,a
50
IL-1β (pg/mg protein)
40 **
**
20
0
Group
Fig. 5. TMJ tissue interleukin 1-
(IL-1
), in pg/mg protein, two
days after injections. See Fig. 2 legend for group definitions.
Statistical significance (ANOVA: P<0.001) was obtained. Post hoc
analysis using Duncan’s multiple range test revealed: **=P<0.01
in comparison with NOT-INJ and SALINE groups; a=P<0.05 in
comparison with CFA-10 g group.
cartilage in response to the inflammatory process in the
joints injected with higher doses of CFA. Again, this
decrease in cartilage thickness is dose dependent and is
similar at the maximum dose to the findings of Mazzier
et al.17 and with our previous findings1. The decrease in
cartilage thickness is apparently due to a reduction in
hypertrophic chondrocytes. The mechanism of this reduc-
tion in hypertrophic chondrocytes may be secondary to an
increased rate of cellular maturation as shown in our
previous studies1.
Tissue swelling during acute inflammation results from
an increase in capillary permeability. Within limits the
magnitude of this swelling can be correlated with the
degree of insult to the tissue. In the present study a
component of the CFA-induced inflammatory response was
swelling of the TMJ and surrounding soft tissues. Rats
Osteoarthritis and Cartilage Vol. 9, No. 7
injected with saline had swelling scores that were compar-
able with non-injected animals. A significant increase in
swelling was noted in the rats receiving the 10 g MT dose
when compared with the control animals. Swelling was
further significantly increased following the 25 g MT dose
in comparison with rats receiving the 10 g MT dose or
control groups. The degree of swelling reached a plateau
as it did not increase further with the 50 g MT dose. A
submaximal level of CFA-induced swelling was, thereby,
achieved with the 10 g MT dose.
Chromodacryorrhea or red tears is due to excessive
production of porphyrins by the Harderian gland in the
rat18. The nasolacrimal duct releases a porphyrin, which
dries around the eyes and external nares. Chromodacry-
orrhea can be produced following acute stress induced by
limb restraint, pain or illness19. Additionally, chromodacry-
orrhea has been suggested to be an indicator of a chronic
underlying disease18. The present data suggest that
stress associated with CFA-induced TMJ inflammation can
also induce chromodacryorrhea. Notably, the intensity of
chromodacryorrhea production appears to be CFA dose-
dependent and may also be used as a measure for the
degree of inflammation in this model.
The cytokine IL-1
has been implicated as a major
inflammatory mediator in a variety of pathological condi-
tions such as rheumatoid arthritis and inflammatory bowel
disease20. IL-1
is produced from a variety of cell types
including monocytes, synovial macrophages and chondro-
cytes20. Patients with temporomandibular disorder show
a higher incidence of elevated IL-1
in TMJ synovial
fluid2,21,22. In the present study retrodiscal TMJ tissue IL-1

was similar in the saline injected and non-injected groups.
Following TMJ CFA injection retrodiscal TMJ tissue IL-1

demonstrated a dose-dependent increase. Retrodiscal
TMJ IL-1
was significantly, and similarly, elevated in the
groups that received the 10 g and 25 g MT doses of CFA
when compared to the control groups. However, IL-1
was
further significantly elevated with the 50 g MT dose. These
data support the hypothesis that a submaximal level of
inflammation can be achieved within the TMJ tissue using
our low doses of CFA as an inflammatory inducing agent.
The plasma concentration of IL-1
in all groups was less
than the detection limit (12 pg/ml) of the assay. This is in
agreement with others23,24, who report non-stressed levels
of IL-1
to be less than 100 pg/ml. The finding that the
plasma concentration of IL-1
was not elevated in the TMJ
CFA injected rats indicates that the CFA did not have a
systemic effect. This is different from the finding that when
a dose identical to our 50 g dose of CFA was injected
systemically, in a hindpaw, plasma IL-1
concentration was
significantly elevated to 650 pg/ml 5 h after injection and
remained elevated (∼600 pg/ml) 10 days later25.
Previously, our laboratory showed that bilateral injection
of a larger dose of CFA than used in the present study
suppressed food intake for up to 5 days and this was
followed by a rebound over-consumption of food that lasted
for 7 days1. In the present study CFA also suppressed the
rats food intake over the 48 h measurement period. On the
first day post CFA injection the 50 g MT dose significantly
suppressed food intake relative to the group receiving the
10 g MT dose. However, even the 10 g MT dose signifi-
cantly suppressed food intake relative to the two control
groups, indicating that the 10 g MT dose, or smaller, could
provide a non-invasive measurable model of inflammation
that would be capable of experimental manipulation. Over
the next 24 h food consumption of the CFA treated groups
increased to similar levels, but their intake was still
623
significantly suppressed when compared with the control
groups. In an earlier study the CFA injected animals
decreased their daily food intake by taking fewer meals
and the intermeal intervals were significantly longer1.
Importantly, the size of the meals taken by the CFA injected
rats was normal, but the duration of the meal was signifi-
cantly extended. Apparently, the CFA-induced inflammation
interfered with the rats initiating meals as demonstrated by
their decreased meal frequency. However, when a CFA
injected rat did initiate a meal they were hungry, as shown
by their normal meal size, but ate slowly due to the stress of
the mechanical chewing process. These data and the
present findings suggest food intake may serve as a
non-invasive marker for CFA-induced TMJ inflammation
and that the response may be dose dependent.
The hypothalamus–pituitary axis and the sympathetic
adrenal medullary system form major homeostatic path-
ways for the regulation of pain and stress26. Glucocorti-
coids are reported to be involved in stress responses and in
homeostasis of the nervous system27. In a previous study
48 h and 6 weeks after receiving bilateral TMJ injections of
CFA, corticosterone was significantly elevated at the begin-
ning of the rats’ inactivity period and significantly sup-
pressed at the beginning of the rats’ activity period1. The
former was confirmed in the present study, where samples
were taken at the beginning of the rats’ inactivity period.
Corticosterone was elevated to a similar degree in the three
groups receiving CFA, and the response was not dose
dependent. An increase in plasma IL-1
can cause an
elevation in plasma corticosterone4,5. Our finding that
plasma IL-1
was not elevated suggests that the increase
in plasma corticosteone caused by TMJ CFA injection in the
present study was not caused by a perpherial release of
IL-1
, but rather by other mechanisms that probably utilized
neural afferent pathways.
CFA-induced TMJ inflammation induces dose-
dependent changes in swelling, chromodacryorrhea and
food intake. These measures may serve as non-invasive
markers for CFA-induced TMJ inflammation/pain. CFA-
induced TMJ inflammation also produces a dose-
dependent change in TMJ tissue histology and TMJ tissue
concentration of IL-1
. The TMJ tissue histology and con-
centration of IL-1
may serve as an invasive marker for
CFA-induced TMJ inflammation/pain. Thus, using our ani-
mal model, the low dose of CFA employed allows the
investigator to experimentally manipulate the inflammation
in a measurable way. The issue of primary concern in this
research was the production of submaximal acute stage
inflammation. The study did not address issues related to
rheumatoid or osteoarthritis and their squealae. Many of
the problems related to intracapsular TMJ disease involve
recurrent episodes of acute inflammation secondary to
macro or micro trauma such as occlusal parafunction. An
animal model with submaximal TMJ inflammation will be
useful in order to test the effects of occlusal factors and
functional micro trauma on joint inflammation. Using this
model later studies will address issues related to degen-
erative inflammatory joint disease. This model of TMJ
inflammation has the potential to be manipulated by extrin-
sic and intrinsic factors. Because TMJ inflammation in our
animal model can be measurably made less or more
severe the potential exists to quantitatively test the thera-
peutic effects of pharmacological agents or the effects of
hormone modulation on TMJ inflammation.
624
Acknowledgments
This work was supported by intramural grants from BCD/
TAMU-HSC and The Center for Craniofacial Research and
Development and by an NIH/NIDCR Individual Predoctoral
Dental Scientist Fellowship (F30DE05726-01 to CAK).
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