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Objective: The purpose of this study is to introduce the application of Cox flexion distraction decompression as an innovative approach to treating knee pain and osteoarthritis. Methods: Six months of clinical files from one chiropractic practice were retrospectively screened for patients who had been treated for knee pain. Twenty-five patients met the criteria for inclusion. The treatment provided was Cox flexion distraction decompression. Pre-treatment and post-treatment visual analog pain scales (VAS) were used to measure the results. In total, eight patients presented with acute knee pain (less than three months' duration) and 18 patients presented with chronic knee pain (greater than three months) including two patients with continued knee pain after prosthetic replacement surgery. Results: For all 25 patients, a change was observed in the mean VAS scores from 7.7 to 1.8. The mean number of treatments was 5.3 over an average of 3.0 weeks. Acute patient mean VAS scores dropped from 8.1 to 1.1 within 4.8 treatments over 2.4 weeks. Chronic patient mean VAS scores dropped from 7.5 to 2.2 within 5.4 treatments over 3.3 weeks. No adverse events were reported. Conclusion: This study showed clinical improvement in patients with knee pain who were managed with Cox flexion distraction decompression applied to the knee.
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J Can Chiropr Assoc 2017; 61(2) 153
ISSN 0008-3194 (p)/ISSN 1715-6181 (e)/2017/153–161/$2.00/©JCCA 2017
Innovative application of Cox Flexion Distraction
Decompression to the knee: a retrospective case
Luigi Albano, BSc, DC1
1 Private practice, Windsor, ON
Corresponding author:
Luigi Albano
Walkerville Chiropractic, 1275 Walker Road, Windsor, ON N8Y 4X9
Tel: 519-258-7979
© JCCA 2017
Objective: The purpose of this study is to introduce the
application of Cox exion distraction decompression
as an innovative approach to treating knee pain and
Methods: Six months of clinical les from one
chiropractic practice were retrospectively screened for
patients who had been treated for knee pain. Twenty-ve
patients met the criteria for inclusion. The treatment
provided was Cox exion distraction decompression.
Pre-treatment and post-treatment visual analog pain
scales (VAS) were used to measure the results. In total,
eight patients presented with acute knee pain (less than
three months’ duration) and 18 patients presented with
chronic knee pain (greater than three months) including
two patients with continued knee pain after prosthetic
replacement surgery.
Results: For all 25 patients, a change was observed
in the mean VAS scores from 7.7 to 1.8. The mean
number of treatments was 5.3 over an average of 3.0
weeks. Acute patient mean VAS scores dropped from
Objectif : Le but de cette étude est de présenter
l’application de la décompression par exion-distraction
de Cox en tant qu’approche novatrice de traitement de
la douleur au genou et de l’arthrose.
Méthodologie : On a inspecté six mois de
dossiers cliniques d’un cabinet de chiropratique
rétrospectivement pour trouver des patients traités pour
une douleur au genou. Vingt-cinq patients respectaient
les critères d’inclusion. Le traitement fourni était la
décompression par exion-distraction de Cox. On a
utilisé des échelles visuelles analogues (EVA) avant et
après le traitement pour mesurer les résultats. Au total,
8 patients présentaient une douleur aiguë au genou
(depuis moins de 3 mois) et 18 patients présentaient une
douleur chronique au genou (depuis plus de 3 mois),
dont 2 patients avec une douleur toujours présente après
la chirurgie de remplacement de prothèse.
Résultats : Pour les 25 patients, on a observé un
changement des résultats moyens de l’EVA de 7,7 à 1,8.
Le nombre moyen de traitements était de 5,3 sur une
moyenne de 3,0 semaines. Les résultats moyens de l’EVA
des patients atteints de douleur aiguë ont chuté de 8,1 à
1,1 après 4,8 traitements sur 2,4 semaines. Les résultats
154 J Can Chiropr Assoc 2017; 61(2)
Innovative application of Cox Flexion Distraction Decompression to the knee: a retrospective case series
The prevalence of knee pain has increased substantial-
ly over a 20 year period, independent of age and body
mass index (BMI).1 It affects approximately 30-40% of
adults by age 65.2 Total knee replacement utilization in
the United States more than doubled from 1999 to 2008.3
Studies have shown that increasing physical activity in
people with osteoarthritis (OA) reduces pain and depres-
sion.4 If a patient has symptoms of OA, such as knee pain
with associated walking disability, he or she may be at
increased risk of premature death from cardiovascular
disease.5 Chiropractic treatment for knee OA is typically
multimodal, involving manipulation, mobilization, soft
tissue techniques, physical therapy modalities, nutritional
counseling, exercise, and orthoses for the knee or foot.6
Cox exion distraction decompression (FDD) of the
spine is an evidence-based, non-surgical spinal care treat-
ment modality, a form of spinal manipulation in which
the human spine is placed in distraction (a type of meas-
ured, controlled traction of the spine) delivered on a spe-
cialized spinal manipulation instrument (the Cox table).7
The main difference between Cox FDD and traction is
that the treatment is manually applied, according to pa-
tient tolerance, with oscillation of the applied forces, all
the while maintaining the joint under decompression (i.e.
tensile loading plus mechanical stress). This can be per-
formed with or without passive stretch to the specic joint
through various ranges of motion (ROM). Its effects on
the spine are well researched and documented. Cox FDD
has demonstrated a reduction of intradiscal pressure of up
to –192mmHg in the lumbar spine and –502mmHg in the
cervical spine.8,9 It is a non-invasive joint therapy for pa-
tients that allows for continued, reasonable daily activity
or minimal convalescence. Recent research has demon-
strated that articular cartilage has the intrinsic ability to
repair itself when the joint is exposed to distraction with
mechanical stimulation.10,11
The application of exion distraction specically to
the knee with and/or without passive knee exion has
not been well documented. The purpose of this study is
to introduce the application of Cox FDD as an innova-
tive approach to the treatment of knee pain and OA. This
study was designed in retrospect to treatment. Chart re-
view of 25 patients is presented.
A retrospective search of patient les over six months was
performed from one chiropractic facility. Ethics approval
was obtained by the Research Ethics Board of the Can-
adian Memorial Chiropractic College. Charts that were
included in this study were patients with only knee pain
and having received Cox FDD applied to the knee with
and/or without passive knee exion. VAS scores were
used to assess treatment effectiveness. Thirty-two charts
were selected. Three were excluded on the basis of having
less than three treatments, and four charts were excluded
for not having nal VAS scores, resulting in 25 patient
records. There were no exclusions based on diagnosis.
8.1 to 1.1 within 4.8 treatments over 2.4 weeks. Chronic
patient mean VAS scores dropped from 7.5 to 2.2 within
5.4 treatments over 3.3 weeks. No adverse events were
Conclusion: This study showed clinical improvement
in patients with knee pain who were managed with Cox
exion distraction decompression applied to the knee.
(JCCA. 2017;61(2):153-161)
key words: knee osteoarthritis, Cox Flexion
Distraction Decompression, knee pain, manual therapy,
manipulation, chiropractic
moyens de l’EVA des patients atteints de douleur
chronique ont chuté de 7,5 à 2,2 après 5,4 traitements
sur 3,3 semaines. Aucun incident indésirable n’a été
Conclusion : Cette étude démontre une amélioration
clinique chez les patients atteints de douleur au genou
qui ont été traités avec la décompression par exion-
distraction de Cox appliquée au genou.
(JCCA. 2017;61(2):153-161)
mots clés : arthrose du genou, décompression par
exion-distraction de Cox, douleur au genou, thérapie
manuelle, manipulation, chiropratique
J Can Chiropr Assoc 2017; 61(2) 155
L Albano
The application of treatment followed similar guidelines
as used in the Cox Technic spinal protocols.8 The treat-
ment involved the patient seated at the Cox Table with the
affected tibiofemoral joint comfortably resting between
the lumbar and dorsal sections of the table (Figure 1). The
dorsal section of the table was placed at an angle between
0-15o below horizontal for comfort and to decrease ham-
string tension. The caudal section was disengaged to al-
low for exion. To create knee joint distraction, the chiro-
practor applied downward forces above the knee and at
the superior aspect of the distal tibiobular joint (Figure
2). The table was distracted to the “taut point” which is
reached when the patient’s knee is distracted to the point
of the barrier of elasticity. This is the starting point of Cox
FDD. The chiropractor controlled the amount of distrac-
tion of the device using a foot switch, applied according
to patient tolerance. The knee was then distracted and
brought to exion and extension as tolerated by the pa-
tient in an oscillatory manner that was smooth and rhyth-
mical for a minimum of 10-15 repetitions (Figures 2, 3,
and 4). Each repetition lasted 2-4 seconds. Total treatment
time with Cox FDD was approximately 1 minute. Most
patients received adjunctive (laser treatment) applied to
the knee joint after each Cox FDD session was complet-
ed. No adverse events were reported.
The age range of the study participants was between 20
and 80 years, with an average age of 57.5. Seventeen of
the eligible charts were considered as chronic with hav-
ing pain greater than three months and eight were con-
sidered acute. Of those, 11 were female and 6 were male.
Fourteen patients (56.0%) had previous knee surgery, all
of which were in the chronic knee pain group: ve me-
niscectomies, two total knee arthroplasties and seven of
unknown surgical type. The acute group was comprised
Figure 1.
Initial setup.
Figure 4.
Back to neutral.
Figure 2.
Flexion Distraction.
Figure 3.
Returning to neutral with distraction.
156 J Can Chiropr Assoc 2017; 61(2)
Innovative application of Cox Flexion Distraction Decompression to the knee: a retrospective case series
of two females and six males. None of the acute patients
had previous knee surgery.
The reduction in VAS scores for both groups are shown
in Table 1. The total average VAS scores for both groups
dropped from 7.7 to 1.8 (a reduction of 5.9) in an aver-
age of 5.3 treatments over 3.0 weeks. Within the chronic
group, the average reduction in VAS scores was from an
initial VAS of 7.5 to 2.2 (a decrease of 5.3 points) in 5.4
treatments over 3.3 weeks. The average reduction in VAS
within the acute group was from an initial VAS of 8.1 to
1.1 (a reduction of 7.0 points) in 4.8 treatments over 2.4
weeks. There were no patients that reported an increase
in pain. One patient did not report any change. None
of the acute cases required any treatment three months
post-treatment. Most of the chronic cases required on-
going maintenance treatments at a frequency of one
treatment per month. In the chronic group, eight out of
17 (47.1%) patients had undergone previous knee surgery
ranging from arthroscopic meniscectomy (n = 6) to total
knee arthroplasty (n = 2).
The Cox 8 Table allows for real-time force measure-
ments during treatment (Figure 5). Hand pressure, dis-
traction force, table angle and distraction distances are
displayed and recorded in real-time as a visual aid. The
force applied along the y-axis during treatment was with-
in 20-40 lbs and table distraction distance was within 16-
55mm. The treatment exion angle ranged between 0o
Table 1.
Change in VAS scores for chronic and acute patients.
Group Average Age
VAS Change
Average No.
Time Span (weeks)
Chronic (n=17) 58.1 7.5 2.2 –5.3 5.4 3.3
Acute (n=8) 49.1 8.1 1.1 –7.0 4.8 2.4
Overall (n=25) 57.5 7.7 1.8 –5.9 5.3 3.0
Figure 5.
Cox 8 table forces
graph applied to
the knee.
J Can Chiropr Assoc 2017; 61(2) 157
L Albano
The primary clinical diagnoses of the patients in both
groups were OA, collateral and cruciate ligament sprains,
meniscus tears and sprains, and post-surgical continued
knee pain for partial and total knee arthroplasty. In many
of the cases there was a combination of these diagnoses.
Retrospective Case Series Findings
Both the acute and chronic knee pain groups in this case
series responded well to treatment. Almost all of the pa-
tients reported a decrease in pain as measured on the VAS
with Cox FDD. Notably, most patients reported immedi-
ate relief after their rst treatment, that lasted from several
hours up to two days. At last follow-up, almost all patients
reported better mobility, knee joint strength and stability.
The last follow-up was performed at 1 to 3 months after
treatment. No adverse reactions were reported by any of
the patients.
The reduction in VAS scores, number of treatments and
duration of care was similar for both groups. Follow-up
treatment was evaluated for both groups. Thirteen of the
chronic cases returned for follow-up treatments within
four weeks and continued with maintenance treatment
every three to four weeks and/or as needed. In reviewing
the acute group, no patients returned for further treatment
after three months.
Previous Studies of Manual Therapy for OA of the
The current study demonstrates a reduction in pain level
and treatment duration that are similar with other studies
involving manual therapy, exercise and/or surgery. Van
den Dolder and Roberts demonstrated a reduction be-
tween –8 to –10 mm versus the control group on 100mm
VAS.12 Treatment consisted of transverse friction to the
lateral retinaculum, patellofemoral stretches, and the ap-
plication of sustained medial glide during repeated ex-
ion and extension of the knee. Maher et al.13 showed a
statistically signicant improvement in ROM but no long-
term changes in pain levels using passive knee exion.
Treatment involved the patient laying prone with the knee
exed and the distal femur secured to the table with a sta-
bilization belt and the therapist applied a traction force to
the knee. Pollard et al.8 demonstrated a reduction in mean
VAS scores from 3.3 to 1.9 in their treatment group. The
intervention group received myofascial mobilization and
an impulse thrust procedure. Deyle et al.14,15 demonstrat-
ed in two randomised controlled trials, improvement in
self-reported pain and function when combining manual
therapy with exercise versus exercise alone. The treat-
ment applied was soft tissue mobilization and stretching.
Khademi-Kalantari et al.16 demonstrated signicant relief
of knee pain with sustained knee joint traction. Finally,
Dwyer et al.17 demonstrated improvement but no sta-
tistical improvement between groups when comparing
manual and manipulative therapy (joint mobilization,
manipulation, and soft tissue treatment) with and without
rehabilitation (monitored and/or home program).
Six weeks of continuous knee joint distraction has also
been shown to postpone the need for total knee joint arth-
roplasty in patients younger than age 65.18 Furthermore,
Van der Woude et al.18 have shown that knee articular car-
tilage has the potential to regenerate, in some cases doub-
ling in thickness with continuous knee joint distraction.
Interestingly, these outcomes were maintained even at 5
year follow-up.18 This could help to partially explain the
clinical results observed in the current study.
Knee Physiology
Similarities exist in the physical properties of the knee and
spinal joints. The knee meniscus and intervertebral discs
are responsible for load transmission, force distribution,
shock absorption, and articular cartilage protection.19 Both
structures rely on collagen brils to resist tensile forces.
Articular cartilage and the extracellular matrix (ECM) are
maintained and produced by chondrocytes, specialized
cells derived from mesenchymal stem-cells. Chondrocytes
produce the cartilage matrix and its components such as
proteoglycans (PGs) and glycosaminoglycans (GAGs),
that provide the tissue with hydration and its high capacity
to withstand compressive loads.20 The most abundant PG
in articular cartilage and the ECM is aggrecan which is
composed of a core protein, hyaluronan (HA), and several
side chains of GAGs. The most abundant GAG side chains
are made up of multiple repeating units of chondroitin-sul-
phates, keratin-sulphates and dermatan-sulphates. The
knee meniscus is predominantly a brocartilaginous struc-
ture reinforced by highly ordered collagen bers in a com-
plex orientation. Compressive forces in the intervertebral
discs are predominately handled by the nucleus pulposus
which is also made up of PGs within a loose framework
158 J Can Chiropr Assoc 2017; 61(2)
Innovative application of Cox Flexion Distraction Decompression to the knee: a retrospective case series
of collagen bers. Changes to the viscosity of HA causes
densication of tissue and can modify the function of fa-
scia, nerve receptors, muscle layers (epimysium and peri-
mysium gliding) and hydrodynamic properties of connect-
ive tissue.21 It is suggested by the authour that the use of
Cox FDD to the knee may cause conformational changes
to the synovial capsule and uid, meniscus, articular carti-
lage, tendons and entheses, due to the decreased pressure
induced by treatment similar to that which occurs in the
intervertebral discs.
Increased levels of catabolic enzymes that degrade the
ECM occur in patients with OA and rheumatoid arthritis
(RA).22 Arachidonic acid metabolites (PGs, leukotrienes,
etc.) and cytokine levels are also increased after inam-
matory insult from injury, infection, or in degenerative
diseases such as OA and RA. These metabolites signal
the biosynthesis of specialized pro-resolving mediators
(SPMs) from omega-3 essential fatty acids including
eicosapentanoic acid and docosahexanoic acid.23 SPMs
resolve inammation (catabasis) as opposed to non-ster-
oidal anti-inammatory medications which block certain
steps of inammation. SPMs initiate healing, contain or
limit inammation, prevent and/or reduce the severity of
inammation, and reduce tissue destruction.24,25 SPMs in-
clude lipoxins, resolvins, protectins and maresins and are
known to act as potent regulators of neutrophil inltra-
tion, cytokine and chemokine production, and clearance
of apoptotic neutrophils by macrophages which promote
the return of tissue homeostasis.25 Stretching of connect-
ive tissue reduces the migration of neutrophils and in-
creases SPM resolvin concentrations.24
Passive neurodynamic mobilization has been shown to
promote nerve function by limiting or altering intraneur-
al uid accumulation, preventing the adverse effects of
intraneural edema.26 The use of mobilization techniques,
such as those used in the current study, may promote heal-
ing of the soft tissues by stimulating the functions of the
nervous system to improve adaptability and decrease tis-
sue sensitivity, thereby helping to alleviate symptoms.27,28
Mechanotransduction is the process by which bio-
mechanical signals (physical forces) regulate or affect cel-
lular activity and behaviour.29,30 Paluch et al.29 describes
it as how cells sense physical forces and translate them
into biochemical and biological responses. Biomechan-
ical signals include compression, stretch (decompression
or tension), and shear forces. These forces are converted
into chemical signals at the cell surface, acting on cell sur-
face adhesion-receptors and calcium ion channels. They
are converted into chemical energy at the cell membrane.
Integrins and cadherins are transmembrane proteogly-
cans that channel mechanotransductive forces and stimuli
along the cytoskeletal laments to distant sites within the
cytoplasm and nucleus.22,23 Genetic transcription of chon-
drocytes increase the production of aggrecan when inu-
enced by mechanotransduction.22,23,30 Mechanotransduc-
tion stimulates mesenchymal stem cells, found throughout
joint tissues, to differentiate into chondrocytes. Chondro-
cytes are also mechanosensitive and under joint distraction
they produce increased levels of PGs, GAGs, and increase
ECM.29-31 It has been shown that mechanical stimulation of
chondrocytes antagonizes interleukin-1β and tumor necro-
sis factor-α.22 Mechanotransduction has also been shown
to reduce the levels of ECM degrading enzymes in OA and
RA. Cox FDD, as used in the current study, applies tensile
and compressive loads to the ligaments, tendons, menisci,
articular cartilage and entheses of the knee all while under
reduced joint pressure from distraction.
Cox Flexion Distraction Decompression
Cox FDD was developed by Dr. James M. Cox, DC, DACBR
over 40 years ago32. Cox Technic is an evidence based
non-surgical, chiropractic spinal manipulation that is ap-
plied using the Cox Table, by a certied practitioner. Sev-
eral National Institute of Health funded studies have dem-
onstrated the effectiveness of the technique in its applica-
tion to the spine.9,32 This is the rst study to document the
treatment on the knee. Cox and Bakkum demonstrated the
treatment applied to the hip joint in treating gemelli-ob-
turator internus complex (GOIC).33 Federally funded re-
search has shown that Cox Technic applied to the spine:
1. Decreases intradiscal pressure in the lumbar
spine up to –192mmHg.34
2. Decreases intradiscal pressure in the cervical
spine up to –502mmHg.35
3. Increases intervertebral disc height.34
4. Increases intervertebral foraminal area up to
Cramer et al.36 demonstrated that spinal joint xation
leads to degenerative changes of the facet joints. Distrac-
tion of the intervertebral disc increases intervertebral disc
J Can Chiropr Assoc 2017; 61(2) 159
L Albano
height, increases perfusion of nutrients, regenerates the
extracellular matrix and reverses degeneration.37-39 Dis-
traction of the knee can regenerate the articular cartilage
and increase the tibiofemoral joint space.11,12,18 The appli-
cation of exion distraction specically to the knee with
and/or without passive knee exion has not been docu-
mented and may yield similar effects as that observed in
the spine. The results of this study suggest that Cox FDD
may be useful in treating patients with knee pain and OA.
This study had also helped to devise a potential protocol
for clinical treatment.
In the most recent published guidelines for non-sur-
gical management of the knee, manual therapy was not
included. The reason provided was that there was insuf-
cient evidence for inclusion.40 A similar conclusion was
made in a systematic review by French et al.41 The Cox
8 table is capable of recording the forces used, exion
angles and distraction distance for each patient. This in-
formation allows for quantiable, standardized treatment
with reproduction of these parameters as well as tracking
of any changes, information that may be useful in future
Study Limitations
The results of this retrospective study must be gauged with
scrutiny, based on the limitations of this study. The deci-
sion to apply Cox FDD to the knee was based on necessity
and not investigative study. Bias in this study is a major
caveat since it was performed in one location by the same
practitioner, and patients underwent Cox FDD without a
control group. As such, it is unknown if the treatment re-
sults in the current study were as a result of the treatment
provided or the natural course of the knee pain disorders.
Moreover, the only distinguishing characteristics between
the different types of knee pain in this study were based
on the classication of acute versus chronic knee pain.
Specic diagnoses of the source of the knee pain were
not part of the inclusion criteria. The groups were not fur-
ther categorized or compared based on individual clinical
diagnosis. The only measure of any changes in pain level
was by the use of VAS which is completely subjective.
Objective tests and standardized questionnaires such as
ROM, WOMAC (Western Ontario McMaster Universities
Arthritis Index) and Stair Climb Test (x-step SCT) would
have provided more reliable measurable data. In addition,
follow-up review for the chronic group in this study was
based on patients returning for care for their knee pain or
other conditions. All of the acute cases were contacted by
telephone or were interviewed during treatment for other
conditions unrelated to the knee by the same clinician.
Telephone follow-up does not provide for actual physical
observation. As well, it skews the pain level by not utiliz-
ing the VAS references for the patient.
All of the patients in this study were also given advice
regarding bracing, exercise and nutrition (an anti-inam-
matory/gluten free diet) . Unfortunately record-keep-
ing of compliance with these recommendations was not
maintained as the patients were not provided or sold any
products by the treating practitioner.
Currently, a 20-patient randomized controlled study is
underway in collaboration with the University of Wind-
sor Faculty of Human Kinetics which uses ROM, WO-
MAC and the Step Test, and patients will be evaluated
before and after treatment. The author also applies Cox
FDD treatment to the hip, shoulder and ankle in his clin-
ical practice. Investigation of the effects on these joints
has not been performed but similar clinical results to the
knee have been observed. Future studies are also planned
in order to investigate the effects of Cox FDD therapy on
knee joint space, specically the meniscus and articular
cartilage, measured via weight-bearing x-ray and MRI.
The results of this study suggest that Cox FDD of the
knee joint may offer benet for patients with knee pain
and/or OA. The use of the Cox 8 table may allow for more
standardized and reproducible treatments. The outcomes
of this study nevertheless necessitate further research in
the form of larger, prospective observational and/or con-
trolled studies to conrm similar results.
I thank Dr. James M. Cox, DC, DACBR and Julie Cox-Cid
for their encouragement and recommendation to investi-
gate and publish the ndings of this study.
Funding sources and potential conict of interest
No funding sources were offered or provided for this
study. Dr Luigi Albano is a chiropractor in private prac-
tice and is a certied Cox Technic provider.
160 J Can Chiropr Assoc 2017; 61(2)
Innovative application of Cox Flexion Distraction Decompression to the knee: a retrospective case series
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[Purpose] This study aimed to examine the effects of self-mobilization techniques for the sciatic nerves on the quality of life in patients with chronic low back pain in the lower limbs accompanied by radiating pain. [Subjects and Methods] The subjects were divided into two groups: a group receiving of lumbar segmental stabilization exercise training including sciatic nerve mobilization techniques, which included 8 males and 7 females, and a group receiving lumbar segmental stabilization exercise training, which included 8 males and 7 females. [Results] There were statistically significant differences in comparison of measurement results between the groups before and after the intervention. [Conclusion] Application of mobilization techniques for the sciatic nerves may promote healing of the soft tissues by stimulating the functions of the nervous system to improve nervous system adaptability and decrease sensitivity, helping to alleviate the symptoms.
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Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. This article is protected by copyright. All rights reserved.
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Mechanotransduction - how cells sense physical forces and translate them into biochemical and biological responses - is a vibrant and rapidly-progressing field, and is important for a broad range of biological phenomena. This forum explores the role of mechanotransduction in a variety of cellular activities and highlights intriguing questions that deserve further attention.
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Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints.
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Objectives: Manual and physical therapists incorporate neurodynamic mobilisation (NDM) to improve function and decrease pain. Little is known about the mechanisms by which these interventions affect neural tissue. The objective of this research was to assess the effects of repetitive straight leg raise (SLR) NDM on the fluid dynamics within the fourth lumbar nerve root in unembalmed cadavers. Methods: A biomimetic solution (Toluidine Blue Stock 1% and Plasma) was injected intraneurally, deep to the epineurium, into the L4 nerve roots of seven unembalmed cadavers. The initial dye spread was allowed to stabilise and measured with a digital calliper. Once the initial longitudinal dye spread stabilised, an intervention strategy (repetitive SLR) was applied incorporating NDMs (stretch/relax cycles) at a rate of 30 repetitions per minute for 5 minutes. Post-intervention calliper measurements of the longitudinal dye spread were measured. Results: The mean experimental posttest longitudinal dye spread measurement (1.1 ± 0.9 mm) was significantly greater (P = 0.02) than the initial stabilised pretest longitudinal dye spread measurement. Increases ranged from 0.0 to 2.6 mm and represented an average of 7.9% and up to an 18.1% increase in longitudinal dye spread. Discussion: Passive NDM in the form of repetitive SLR induced a significant increase in longitudinal fluid dispersion in the L4 nerve root of human cadaveric specimen. Lower limb NDM may be beneficial in promoting nerve function by limiting or altering intraneural fluid accumulation within the nerve root, thus preventing the adverse effects of intraneural oedema.
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Advances in our understanding of the mechanisms that bring about the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators that include the lipoxin, resolvin, protectin and maresin families, collectively called specialized pro-resolving mediators. Synthetic versions of these mediators have potent bioactions when administered in vivo. In animal experiments, the mediators evoke anti-inflammatory and novel pro-resolving mechanisms, and enhance microbial clearance. Although they have been identified in inflammation resolution, specialized pro-resolving mediators are conserved structures that also function in host defence, pain, organ protection and tissue remodelling. This Review covers the mechanisms of specialized pro-resolving mediators and omega-3 essential fatty acid pathways that could help us to understand their physiological functions.
Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury "from within" and chronic changes that may prove both morbid and fatal. The resolution phase of inflammation, once thought to be a passive event, is now known to be a highly regulated, active, and complex program that terminates the inflammatory response once the threat has been contained. Specialized pro-resolving mediators (SPMs) are biosynthesized from omega-3 essential fatty acids to resolvins, protectins, and maresins and from omega-6 fatty acids to lipoxins. Through cell-specific actions mediated through select receptors, these SPMs are potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages, promoting a return to tissue homeostasis. This process appears to be defective in several common human lung diseases, such as asthma and COPD, which are characterized by chronic unrestrained inflammation and significant associated morbidity. Here, we highlight translational research in animal models of disease and with human subjects that sheds light on this rapidly evolving area of science and review the molecular and cellular components of the resolution of lung inflammation.
The purpose of this study was to examine the methodological integrity, sample size requirements, and short-term preliminary clinical outcomes of manual and manipulative therapy (MMT) in addition to a rehabilitation program for symptomatic knee osteoarthritis (OA).Methods This was a pilot study of an assessor-blinded, randomized, parallel-group trial in 2 independent university-based outpatient clinics. Participants with knee OA were randomized to 3 groups: 6 MMT sessions alone, training in rehabilitation followed by a home rehabilitation program alone, or MMT plus the same rehabilitation program, respectively. Six MMT treatment sessions (provided by a chiropractic intern under supervision or by an experienced chiropractor) were provided to participants over the 4-week treatment period. The primary outcome was a description of the research methodology and sample size estimation for a confirmatory study. The secondary outcome was the short-term preliminary clinical outcomes. Data were collected at baseline and 5 weeks using the Western Ontario and McMasters Osteoarthritis Index questionnaire, goniometry for knee flexion/extension, and the McMaster Overall Therapy Effectiveness inventory. Analysis of variance was used to compare differences between groups.ResultsEighty-three patients were randomly allocated to 1 of the 3 groups (27, 28, and 28, respectively). Despite 5 dropouts, the data from 78 participants were available for analysis with 10% of scores missing. A minimum of 462 patients is required for a confirmatory 3-arm trial including the respective interventions, accounting for cluster effects and a 20% dropout rate. Statistically significant and clinically meaningful changes in scores from baseline to week 5 were found for all groups for the Western Ontario and McMasters Osteoarthritis Index (P ≤ .008), with a greater change in scores for MMT and MMT plus rehabilitation. Between-group comparison did not reveal statistically significant differences between group scores at week 5 for any of the outcome measures (P ≥ .46).Conclusions This pilot trial suggests that a confirmatory trial is feasible. There were significant changes in scores from baseline to week 5 across all groups, suggesting that all 3 treatment approaches may be of benefit to patients with mild-to-moderate knee OA, justifying a confirmatory trial to compare these interventions.
To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis, intended to inform patients, physicians, and allied health care professionals worldwide. Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the osteoarthritis (OA) literature, twenty-nine treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OARSI evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using AMSTAR criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical subphenotypes. Consensus recommendations were produced using the Rand/UCLA Appropriateness method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical subphenotypes and accompanied by 1-10 risk and benefit scores. Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical subphenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral NSAIDs (COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical subphenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.