S490 Abstracts / Osteoarthritis and Cartilage 27 (2019) S373eS516

Conclusions: For the outcome responders to therapy, defined by the
OMERACT-OARSI criteria, a small and statistical significant effect was
seen for exercise therapy compared to no or minimal intervention in
patients with hip OA post-treatment. The risk difference of 0.13 means
that 7.7 patients should receive exercise therapy to gain one responder.
At 6 months after treatment this small effect was still visible, but no
effect was seen anymore at 12 months after treatment. More (sensi-
tivity)analyses will follow to gain more insight in the reasons for this
small effect, like type of exercise therapy, compliance, patient selection,
or the definition of responder criteria itself.
the KOA and Placebo groups. There were no differences in synovial
score and fibrosis in the synovial membrane of KOA groups.
Conclusions: Clinical-like cryotherapy improves the gait function and
reduces the number of leukocytes and inflammatory cytokines in
synovial fluid of rats with ACLT-induced KOA. These results provide new
evidence of the beneficial effects of cryotherapy and suggest it can be
used as a non-pharmacological and complementary treatment to con-
trol joint inflammation of KOA.

707
CLINICAL-LIKE CRYOTHERAPY IMPROVES GAIT FUNCTION AND
REDUCES SYNOVIAL INFLAMMATION IN RATS WITH KNEE
OSTEOARTHRITIS
G.M. Barbosa 1, J.E. Cunha 1, P.A. Castro 1, T.M. Cunha 2, F.F. Oliveira 2,
~o Carlos, Sa
F.Q. Cunha 2, F.S. Ramalho 2, T.F. Salvini 1. 1 Federal Univ. of Sa ~o
Carlos, Brazil; 2 Univ. of Sao Paulo, Ribeira~o Preto, Brazil
Purpose: To evaluate the effects of clinical-like cryotherapy on gait
function and synovial inflammation in rats with knee osteoarthritis
(KOA) induced by anterior cruciate ligament transection (ACLT).
Methods: The experimental protocol was in accordance with the
National Guide for the Care and Use of Laboratory Animals (National
Research Council, 1996). All procedures were approved by the institu-
tional Ethics Committee and conducted by trained professionals blin-
ded to the identity of the experimental groups. Two-month-old male
Wistarrats (n¼32; 297±25 g) were studied. The animals were housed in
pathogen-free conditions at 24ºC±1 C under a reverse light cycle (12/12
light/dark) with free access to standard rat chow and water. Animals
were randomly allocated into four groups (n¼8 per group): Control
(without surgery and intervention); ACLT knee surgery (KOA); ACLT
knee surgery submitted to ice pack (KOAþCryotherapy), and ACLT knee
surgery submitted to a sand pack (KOAþPlacebo). An adapted ACLT-
induced KOA model was used. The groups were analyzed one day before
and 60 days after ACLT surgery from the least to the most stressful tests:
skin temperature (thermography), gait test (paw print), thermal
response threshold (hotplate) and swelling (digital caliper). Next, both
the KOAþCryotherapy and KOAþPlacebo groups underwent the inter-
ventions (ice pack or sand pack) twice a day, for 20 min each, over five
consecutive days (from the 61st to the 65th days). The four groups were
then assessed on the 66th day, and after euthanasia, the synovial fluid
(account of leukocytes and cytokine levels) and synovial membrane
(histopathological analysis) were collected (Figure 1).
Results: Among the KOA groups, only the Cryotherapy group increased
their paw contact area (P¼0.004; 14%) after interventions, with no
difference in relation to the Control group [Figure 2(A)]. Cryotherapy
decreased the number of leukocytes (P<0.001; 95.0%; Figure 3) and
cytokine levels (P<0.001; 55%; Figure 4) in synovial fluid in relation to
 Abstracts / Osteoarthritis and Cartilage 27 (2019) S373eS516 S491

708 joint. Subsequent studies will determine how procedural pain from
EFFECTS OF SKIN COOLING ON INTRA-ARTICULAR KNEE trans-capsaicin injection into an osteoarthritic knee relates to joint
TEMPERATURE IN HEALTHY SUBJECTS temperature.
R.M. Stevens 1, J.N. Campbell 1, K. Guedes 1, N. Mistry 1, D.X. Lascelles 1,
D. Ball 2. 1 Ctr.xion Therapeutics Inc., Boston, MA, USA; 2 MAC Clinical Res.,
Manchester, United Kingdom
Purpose: Cooling is widely used to control pain associated with acute
injury and surgery involving the knee. Cooling may affect pain by
exerting effects on the inflammatory cascade, transduction channels in
nociceptors, sodium channel activity in neurons, or may suppress pain
through masking effects mediated by central mechanisms. CNTX-4975,
a highly purified, synthetic trans-capsaicin, is under investigation in
phase 3 trials to determine efficacy and safety when administered via
intra-articular (IA) injection in patients with moderate to severe knee
osteoarthritis pain. Cooling has been demonstrated to decrease pain
associated with topical capsaicin without interfering with the ther-
apeutic response. In other studies, it has been determined that cooling
markedly decreases the initial pain associated with capsaicin injection.
Here we report temperature variations of both the skin and the IA space
in healthy volunteers using 2 different cooling techniques currently 709
used in clinical practice IMPACT OF PRIOR KNEE SURGERY ON REDUCTION IN KNEE PAIN
Methods: Two knee cooling techniques were used in healthy volun- FOLLOWING EDUCATION AND SUPERVISED EXERCISE THERAPY:
teers: an ice pack placed on the patella of one knee, and a commercially ANALYSIS OF 13,120 PATIENTS WITH KNEE OSTEOARTHRITIS
available circumferential circulating ice water wrap (CCIWW) placed on K. Pihl 1, S.T. Skou 1, 2, D.T. Grønne 1, E.M. Roos 1. 1 Dept. of Sports Sci. and
the skin surrounding the other knee. To reduce bias from order effects, 3 Clinical Biomechanics, Univ. of Southern Denmark, Odense, Denmark;
2
subjects received the CCIWW on the left knee and ice pack on the right, Dept. of Physiotherapy and Occupational Therapy, Næstved-Slagelse-
and the other 2 subjects received ice pack cooling on the left knee and Ringsted Hosp., Slagelse, Denmark
CCIWW on the right. Two temperature probes were used for each knee:
Purpose: To determine the impact of prior knee surgery on change in
an IA probe and a skin probe placed adjacent to the superior pole of the
self-reported knee pain intensity after participation in an eight-week
patella under the cooling apparatus. After baseline temperature meas-
combined patient education and supervised exercise therapy program.
urements in the left knee, cooling was applied for 15 minutes, at which
Methods: We used data from the Danish Good Life with osteoArthritis
point subjects received an IA injection of 15 mL of 2% lidocaine without
in Denmark (GLA:D®) registry. Patients with knee osteoarthritis (OA)
epinephrine (to simulate the procedures used with the CNTX-4975 IA
and available data on previous knee surgery and complete baseline and
injection procedure). IA CNTX-4975 was not administered. Cooling was
three months data on self-reported knee pain intensity were included.
restarted and continued up to a total of 120 minutes. The process was
Prior surgery to the index knee (i.e. most affected knee when entering
repeated for the right knee after a rest period (4 hours) following left
the GLA:D® program) was assessed by the physical therapist by asking
knee measurements. Temperatures within the knee were measured at
the patients about prior surgery and type of surgery. We classified
approximately 5-minute intervals from probe placement until removal.
surgery types into six groups: arthroscopy (i.e. surgery to the meniscus,
Probe removal was approximately 30 minutes following cessation of
removal of loose bodies, synovectomy, debridement, microfracture, and
cooling. Subjects were asked to rate their pain using a numeric pain
diagnostic arthroscopy), reconstruction of the anterior and/or posterior
rating scale (0-10; 0¼no pain; 10¼worst imaginable pain) at various
cruciate ligaments (ACL/PCL), surgery to the patellae (i.e. stabilization
time points throughout the procedure. At subsequent visits, knees were
and other surgeries to the patellae), osteotomy, knee replacement (KR),
inspected for any injection site issues, and adverse events were
and other surgeries (including surgery to the collateral ligaments and
recorded.
patellae tendon). As some patients had had more than one surgical
Results: Five healthy male subjects were enrolled; mean age, 30 years.
procedure they were classified according to the most invasive one (i.e.
All subjects completed the study for both knees. The Figure shows the
KR being the most invasive, then osteotomy, surgery to the patellae,
mean temperature change at the skin surface and in the joint over time
ACL/PCL reconstruction, and the least invasive being arthroscopy).
under the 2 cooling conditions. The mean baseline skin and IA tem-
Average knee pain intensity during the last month was measured at
peratures were approximately 29 C and 33 C, respectively. The
baseline and immediately after the treatment program using a 100 mm
decrease in skin temperature was similar between techniques for the
visual analogue scale (VAS) where 0 corresponds to ‘no pain’ and 100 to
first 40 minutes, reaching a temperature of approximately 22 C. With
‘maximum pain’. The main outcome was the between-group difference
the ice pack, the skin temperature plateaued after 50 to 60 minutes and
in change in pain intensity from baseline to after the treatment program
had a temperature of 19 C at 140 minutes when cooling was removed.
between patients with or without prior surgery to the index knee. This
In contrast, with the CCIWW technique, the skin temperature continued
was analyzed using a linear regression model adjusted for age, sex, body
to decrease to 14 C at 140 minutes. The ice pack did not have an
mass index (BMI), educational level, number of comorbidities, problems
appreciable effect on the IA temperature at any point. With the CCIWW
in other knee or hip joints, and number of bodily pain areas. A between-
technique, 40 minutes after the start of cooling, the mean IA knee
group difference of 10 mm was considered clinically important. In a
temperature had decreased by approximately 2 C, and by 140 minutes
subgroup of patients with available data on the type of surgery, the
had decreased by approximately 10 C to a temperature of 23.9 C (95%
analysis was repeated comparing the different surgery types with
CI, 22.6-25.2). Even after the cooling was stopped, there was a delay
patients not having had previous surgery.
before the IA temperature began to rise. Subjects reported no pain from
Results: A total of 13,120 patients with knee OA were included in the
either the skin or the joint. The procedures overall were well tolerated
main analysis (mean age 64 (SD 9.5), 72% women) of which 3,925
and there were no complications.
patients (30%) had had one or more prior knee surgeries. Mean knee
Conclusions: The baseline knee IA temperature under ambient con-
pain intensity at baseline was 47.9 (SD 21.8) (Table 1) and the overall
ditions was considerably below core temperature and approximately
reduction in pain following the eight-weeks patient education and
33 C. The mean baseline skin temperature overlying the joint was
exercise therapy program was 13.0 (22.9). No clinically relevant differ-
approximately 29 C. Circumferential cooling provided by the CCIWW
ence in pain reduction was observed between patients with or without
technique was superior to cooling with the ice packs, resulting in a 9 C
prior knee surgery (unadjusted mean difference 0.7, 95% CI: -0.2 to 1.5,
decrease in skin temperature and an approximate 10 C decrease in joint
adjusted mean difference 1.1, 95% CI 0.2 to 2.0, and fully adjusted mean
temperature over 140 minutes. Although there was initially a lag,
difference 1.3, 95% CI: 0.4 to 2.2). In the subgroup analysis, patients
decreases in joint and skin temperature were temporally parallel. The
having had surgery to the patellae had larger reduction in pain than
thermal inertia was such that the IA temperature decreased even after
patients not having had prior surgery, while those having had KR had
cessation of cooling before it began to rise. Effective joint cooling
less reduction than those not having had prior surgery. In both
appears to favor a method that provides circumferential cooling of the