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Background: Cryotherapy is one of the most popular electro-physical agents used to 'treat' acute inflammation after a soft tissue injury. Much of the clinical rationale for this is based on anecdotal reports, with most clinicians accepting that cryotherapy has an 'anti' inflammatory effect after injury. There have been a number of recent advances towards improving our understanding of the inflammatory process after soft tissue injury. Objectives: To review the rationale for cryotherapy intervention in the acute phases of soft tissue injury, whilst considering physiological, cellular and molecular models of inflammation. Methods: Qualitative review of recent evidence. Results: Research is restricted to animal models, applying various forms of cryotherapy after induced soft tissue injury. Outcomes focus on the effect that cooling has on key physiological, biochemical and molecular inflammatory events including: secondary cell death, white blood cell behaviour, apoptosis, blood flow and oedema formation. Conclusion: Cryotherapy can have an influence on key inflammatory events at a cellular and physiological level after an acute soft tissue injury. However, the relative benefits of these effects have yet to be fully elucidated and it is difficult to contextualize within a human model. It is important to continue to update our rationale for applying common electro-physical agents such as cryotherapy after acute soft tissue injury, based on contemporary models of inflammation.
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Systematic Review
Cryotherapy and inflammation: evidence
beyond the cardinal signs
Chris M. Bleakley
1
, Gareth W. Davison
2
1
Health and Rehabilitation Sciences Research Institute and
2
Sport and Exercise Sciences, Research Institute,
University of Ulster, Northern Ireland
Background: Cryotherapy is one of the most popular electro-physical agents used to ‘treat’ acute
inflammation after a soft tissue injury. Much of the clinical rationale for this is based on anecdotal reports,
with most clinicians accepting that cryotherapy has an ‘anti’ inflammatory effect after injury. There have
been a number of recent advances towards improving our understanding of the inflammatory process after
soft tissue injury.
Objectives: To review the rationale for cryotherapy intervention in the acute phases of soft tissue injury,
whilst considering physiological, cellular and molecular models of inflammation.
Methods: Qualitative review of recent evidence.
Results: Research is restricted to animal models, applying various forms of cryotherapy after induced soft
tissue injury. Outcomes focus on the effect that cooling has on key physiological, biochemical and
molecular inflammatory events including: secondary cell death, white blood cell behaviour, apoptosis,
blood flow and oedema formation.
Conclusion: Cryotherapy can have an influence on key inflammatory events at a cellular and physiological
level after an acute soft tissue injury. However, the relative benefits of these effects have yet to be fully
elucidated and it is difficult to contextualize within a human model. It is important to continue to update our
rationale for applying common electro-physical agents such as cryotherapy after acute soft tissue injury,
based on contemporary models of inflammation.
Keywords: Cryotherapy, Acute injury, Soft tissue, Inflammation
Introduction
Cryotherapy is one of the simplest and oldest
modalities for treating soft tissue injuries such as
sprains, contusions, and dislocations. The immediate
phase after soft tissue injury is characterized by an
acute inflammatory response. This often presents
clinically with cardinal signs such as heat, redness,
pain and swelling. Few clinicians may look beyond
these cardinal signs when providing justification for
intervention; and it is commonly accepted that
cryotherapy has an ‘anti’ inflammatory effect after
soft tissue injury. Applying a cold agent to a hot and
red tissue may seem pragmatic; however, there is not
always an obvious link between inflammation visible
under the microscope and that clinically apparent
and characterized by the original cardinal signs.
1
Paradoxically, recent trends in sports medicine
involve delivering growth factors into healing muscle
tissue (e.g. via platelet rich plasma or autologous
blood injections)
2
which seems to lean more towards
a pro-inflammatory treatment approach.
Our aim is to review the rationale for cryotherapy
intervention in the acute phases of soft tissue injury,
whilst considering physiological, cellular and mole-
cular models of inflammation. Where appropriate,
relevance to injured human subjects will be assessed,
and recommendations for future research provided.
Search Strategy
In January 2010, we undertook a computerized literature
search on Medline, EMBASE and Cochrane Central
Register of Controlled Trials (CCTR) (via OVID) using
nine key words and subject headings relating to
cryotherapy. This was supplemented with ‘related article’
searches on PubMed, and biblography tracking.
Relevant studies were extracted, with exclusions made
based on titles, abstracts or full text versions. No
restrictions were made on study design or type/mechan-
ism of acute soft tissue injury. Relevant outcomes were
any physiological, cellular or molecular measurement
associated with inflammation; recorded before injury,
and up to one week post-injury. No restrictions were
made on the type/dosage of cryotherapy intervention.
Correspondence to: Chris Bleakley, Health and Rehabilitation Sciences
Research Institute, School of Health Sciences, University of Ulster, Shore
Road, Newtownabbey, Co Antrim, BT37 OQB, Northern Ireland. Email:
chrisbleakley@hotmail.com
430
ßW. S. Maney & Son Ltd 2011
DOI 10.1179/1743288X10Y.0000000014 Physical Therapy Reviews 2010 VOL.15 NO.6
Table 1 provides details of the cryotherapy inter-
ventions and reported outcomes across studies.
Qualitative comparisons were made and results were
grouped and discussed by outcome.
Secondary Cell Injury
Perhaps the most commonly cited rationale for
applying ice after acute soft tissue injury relates to the
‘secondary injury model’.
3
This is based on the premise
that after an initial trauma (e.g. muscle strain or
contusion), the patho-physiological events associated
with acute inflammation can induce secondary damage
to cells around the injury site. Of particular concern is
that this can involve collateral damage to healthy cells
not injured in the initial trauma. This phenomenon is
known as secondary cell injury, and may be caused by
both enzymatic and ischaemic mechanisms.
4
One of the
most important cellular effects associated with
cryotherapy is its potential to reduce the metabolic
rate of tissue at, and surrounding the injury site. This
reduction in metabolic demand may allow the cells to
better tolerate the ischaemic environment in the
immediate phases after injury thus minimizing the
potential for secondary cell injury or death.
Table 1 Details of cryotherapy intervention and reported outcomes
Author
Details of cryotherapy
intervention Directness of cooling
Time after injury
of ice initiation
Outcomes
(blinded assessor Y/N)
Osterman et al.
5
CWI (ice and isotonic
saline); duration up to
13 hours (until ATP
depletion)
Amputated limb with
a single layer of
plastic wrap (mean
intramuscular
temperature: 1.2uC)
Immediately post
amputation
ATP/PCr
depletion (N)
Sapega et al.
6
CWI (isotonic saline at
1, 10, 15 and 22uC);
duration 45 minutes, up to
13 hours
Amputated limb
with a single layer of
plastic wrap
(intramuscular temperature as
low as 0.5–1uC)
Immediately post
amputation
ATP/PCr depletion;
pH (N)
Farry et al.
17
Crushed and compression,
20 minutes62
Intact skin Immediate (likely) IHA (Y)
Hurme et al.
18
Cold pack with
compression and elevation;
5 minutes every 1464
Intact skin (lowest
temperature recorded
in deep muscle: 20uC)
Immediate IHA (Y)
Smith et al.
22
Ice cylinders;
20 minutes
every 6 hours63
Intact unshaven skin Immediate (likely) Intravital microscopy
with MC (Y)
Laser Doppler
fluxmetry
Curl et al.
29
Ice cylinders;
20 minutes
every 6 hours for 2 days
Intact skin 5 minutes Intravital
microscopy
with MC
Laser fluxmetry (N)
Dolan et al.
30
CWI in 12.8–15.6uC;
30 minutes64
CWI to intact
shaved limbs
5 minutes Water
displacement (N)
Merrick et al.
7
Ice pack with elastic tape;
5 hours
Unshaven intact skin Immediate (likely) Biochemical
assay (N)
Westermann et al.
13
Ice cold saline solution;
1 hour duration
Through MC,
muscle surface
temperature
decreased to 10¡2uC
Immediate Intravital
microscopy
with MC (N)
Deal et al.
31
Cylinder of ice to skin side
of MC; 20 minutes
Unshaven intact skin 15 minutes Intravital
fluorescent
microscopy with
MC (N)
Dolan et al.
30
CWI at 12.8uC; 3 hours,
followed by 1 hour rest
CWI intact
shaven limbs
5 minutes Water
displacement (N)
Lee et al.
14
Saline at 3uC; 10 minutes Cooling directly
onto exposed
muscle surface
5 minutes Intravital
microscopy (N)
Real time laser
scanning
Schaser et al.
15
Saline at 8uC; 20 minutes Direct to surgically
exposed muscle
(muscle surface
temperature
cooled to 10uC)
Immediate (likely) Intravital
microscopy
IHA (Y)
Schaser et al.
16
Saline at 8uC; 6 hours Shaven intact skin
(muscle surface
temperature
cooled to 10uC)
Immediate (likely) Intravital microscopy
IHA (Y)
Note: CWI, cold water immersion; IHA, immunohistological analysis; MC, microvascular chamber; ATP, adenosine triphosphate; PCr,
phosphocreatine.
Immediate (likely): although not stated specifically, it was likely based on the experimental set-up.
Bleakley and Davison Cryotherapy and inflammation
Physical Therapy Reviews 2010 VOL.15 NO.6 431
Evidence to support secondary injury theory is
based largely on studies of limb preservation. Sapega
and colleagues
5,6
used phosphorous-31 nuclear mag-
netic resonance imaging to monitor cellular metabo-
lism in ischaemic (amputated) cat limbs, stored for up
to 10 hours, at a range of temperatures between 22
and 1uC. Limbs were removed at hourly intervals for
rescanning; overall, results showed that muscle cells
survived better at lower muscle temperatures. This
was exemplified by lower levels of adenosine tripho-
sphate (ATP) and phosphocreatine depletion, and
lower levels of acidosis, during the period of
ischaemia. Of note, these effects appeared to be
reversed at more extreme muscle temperatures
reductions below 5uC. This was attributed to extre-
me temperature reductions causing inhibition of
the calcium pump of the muscle’s sarcoplasmic
reticulum.
6
In a more recent and related study, Merrick and
colleagues
7
tried to quantify the effect of cryotherapy
on mitochondrial function after injury. Specifically
they measured the activity of the mitochondrial
enzyme, cytochrome c oxidase, after experimental
crush injury; comparing outcomes in cold treated and
untreated muscle tissue. Fitting with the ‘secondary
injury model’, 5 hours of continuous cooling with a
crushed ice pack inhibited the loss of mitochondrial
oxidative function after injury when compared to the
untreated controls. Although the model used by
Merrick et al.
7
is not directly determining the effects
of cryotherapy on the inflammatory process or
muscle injury per se, it is the first study to have
taken a novel approach to indirectly assess the effects
of secondary generated free radicals, and their
possible interference with enzymes controlling oxida-
tive phosphorylation (cytochrome c oxidase) and thus
ATP production after injury.
White Blood Cells (WBCs)
When muscle or joint injury occurs, phagocytic white
cells, such as neutrophils, monocytes, eosinophils ad
macrophages become activated and dominate the
inflammatory response in the early stages. Although
these cells have a critical role in healing through their
removal of necrotic debris and release of cytokines;
8
they can also have a negative effect on soft tissue
healing after injury.
8,9
For example, white cell
activation results in a series of reactions termed the
‘respiratory burst’.
10
These reactions are a source of
reactive oxygen species (ROS) such as superoxide
(O{
2), hydrogen peroxide (H
2
O
2
) and hydroxyl (OH
.
);
and hypochlorous acid (HOC1) which is a powerful
antibacterial agent. In certain circumstances the
production of ROS and antibacterial agents are
important immune defense mechanisms; however,
they can also be a potentially dangerous mechanism if
inappropriately activated. For example, overproduc-
tion of ROS may cause unwanted collateral damage
to adjacent tissues and surrounding molecules.
11
This
may be particularly likely in the event of a closed soft
tissue injury such as an ankle sprain, which is not
associated with bacteria or infection. Indeed, there is
evidence that blocking the respiratory burst, using
anti-CD11b antibody (M1/70), produces a three-fold
reduction in myofibre damage in an animal model at
24 hours post-injury.
12
Interestingly, a number of animal models have
studied the effect that crotherapy has on WBC
behaviour after soft tissue injury. A popular
approach has been to use fluorescent intravital
microscopy
13–16
to observe the effect that ice has on
leukocyte activity within the microvasculature. These
studies found a clear trend that icing significantly
lowered the percentage of both adherent and rolling
neutrophils after injury, in comparison to injured
untreated tissue. This finding was consistent over the
first 24 hours after injury.
13–16
Other animal models
7,15–18
have undertaken histo-
logical analysis on excised tissue after soft tissue
injury. In each case, various staining techniques were
used to identify leukocyte sub-types at the injury site.
Again each study made comparisons between ice
treated, and untreated injured tissue samples. Using
an injured ligament model and assessor blinding,
Farry et al.
17
found that ice treated groups had lower
levels of WBCs (polymorphs, lymphocytes and
plasma cells) at 48 hours, in comparison to injured
contra-lateral untreated limbs. Hurme et al.,
18
who
also used blinded outcome analysis, found that at
various time points post-injury, the ice treated animal
tissue had lower levels of erythrocytes (1 hour),
neutrophils (6 hours) and macrophages (at 24 hours)
in comparison to the untreated control limbs.
Although Schaser et al.
15
also found cooling
decreased neutrophilic granulocyte muscle infiltra-
tion, in comparison to control muscle, there were
higher levels of macrophages. In a follow-up study
16
using longer periods of cooling (5 hours), tissue
analysis at 24 hours post trauma also found lower
levels of neutrophilic granulocytes in the cold treated
muscle.
Although the examination of adherent and rolling
neutrophils following injury and cryotherapy may, in
some instances, be beneficial, these models must be
developed if we are to further our understanding in
this area. It may be more relevant for future research
to quantify the amount of direct neutrophil activation
that occurs following injury. This approach may allow
for estimation as to how much secondary cell and
surrounding tissue damage and inflammation will
likely occur. A popular marker that is commonly used
to determine neutrophil activation is myeloperoxidase.
Bleakley and Davison Cryotherapy and inflammation
432 Physical Therapy Reviews 2010 VOL.15 NO.6
This is produced by an increase in ROS activity and it
has been successfully used in studies looking at free
radical production and immune response after stretch
injury in animal skeletal muscle.
19
Apoptosis
Apoptosis is a programmed cell death. It is char-
acterized by a cascade of biochemical events cumu-
lating in altered cell morphology and eventual cell
death. Although apoptosis is the normal means by
which cells die at the end of their life span, its
incidence may be affected by soft tissue injury.
Higher numbers of apoptotic cells have been
recorded around the edges of rotator cuff tears when
compared to un-injured control muscles.
20
The
reasons for this increase have not yet been fully
elucidated; however, the accumulation of reactive
oxygen species in injured tissue (oxidative stress)
could again play a significant role.
21
Cell survival
requires multiple factors, including appropriate pro-
portions of molecular oxygen and various antiox-
idants. Although most oxidative insults can be
overcome by the cell’s natural defenses, sustained
perturbation of this balance may result in apoptotic
cell death.
There is limited evidence from animal models that
cryotherapy can reduce the incidence of apoptosis
after injury. Westermann et al.
13
found that after
chemically induced inflammation, the number of
apoptotic muscle cells (quantified by the number
with nuclear condensation and fragmentation) was
significantly higher in untreated controls, when
compared to the cryotherapy group (muscle surface
cooled to 10uC). This is an interesting finding as
reduced levels of apoptosis may again represent a
protective effect of cryotherapy after soft tissue
injury. We can only postulate as to the reasons for
this finding; however, this may be further evidence
that cryotherapy can reduce inflammation and
decrease secondary free radical production (from
the respiratory burst), thereby causing less interfer-
ence with important proteins and other cell metabo-
lites that control apoptosis.
Blood Flow and Oedema
Acute soft tissue injury incurs a multitude of changes
to the microvasculature. These include: increased
vessel diameter;
16,22
increased cell permeability and
macromolecular leakage into the injured tissue;
16
and
decreased tissue perfusion.
13,15,16
Paradoxically, there
is clear evidence that ice has a vasocontrictive response
in human tissue based on impedance plethysmography
outcomes.
23,24
Recent studies
25–28
also confirm that
topical cooling has a similar effect on deep tissue
haemodynamics, causing significant reductions in
capillary blood flow, with facilitated venous capillary
outflow in healthy humans. It is important to consider
if cryotherapy can reverse the effects that soft tissue
injury has on tissue haemodynamics using injured
models. Again much of the evidence in this area is
based on animal models.
Using intravital microscopy, some studies found
that ice application did not significantly change
capillary diameter,
15,16
arteriole diameter,
15,22,29
or
capillary velocity after injury.
15,16
In contrast, others
found that ice either significantly increased
15
or
decreased
13
arteriole diameter after injury.
There may be clearer patterns associated with
venular diameters. Three studies
14–16
reported smaller
venular diameters in ice treated groups in comparison
to injured (untreated) controls when measured at
both the initial stages
14,15
and at 24 hours
16
post-
injury. In two of these studies,
14,16
the differences
were significant, and in one case, venular diameter in
the cold group had returned to pre-injury levels.
16
Although this trend is supported with evidence that
iced tissue also had higher levels of venular blood
flow velocity in comparison to controls in the
immediate stages post-injury,
13–15
this trend was
reversed at 24 hours post-injury.
There is also conflicting evidence on the effect that
cryotherapy has on tissue perfusion post-injury.
Using fluorescent microscopic assessment of the
functional capillary density (length of erythrocyte-
perfused capillaries per observation area), three
studies
13,15,16
found that ice application significantly
increases tissue perfusion after injury, in comparison
to untreated injured controls. Again, in two
cases,
15,16
perfusion was restored to pre-injury levels.
In contrast, based on laser Doppler imaging after
injury, Curl et al.
29
found that cooling had little effect
on microvascular perfusion.
Using a related outcome measurement, Schaser and
colleagues
15,16
monitored intramuscular pressures in
rat limbs after soft tissue injury, randomizing limbs to
receive either cold saline, or no intervention. Lower
intramuscular pressures [17.7 mm Hg (SD: 4.7)] were
recorded at 1.5 hours post-injury in the cooling group
(treated with 20 minutes of saline cooling), when
compared to untreated controls [19.2 mm Hg (SD:
3.1)]. Their follow-up study also found that longer
periods of muscle cooling (5 hours) was associated
with lower intramuscular pressures
18
(95% CI: 5.5 mm
Hg) in comparison to untreated controls [26 (95% CI:
1.9 mm Hg)], at 24 hours post-injury.
Limitation and Future Study
There are a number of shortcomings associated with
the current evidence base, particularly when we try to
relate these findings to the injured human subject.
Primarily, much of the research relies on animal
models, applying various forms of cryotherapy after
an induced ‘crush type’ soft tissue injury. Furthermore,
Bleakley and Davison Cryotherapy and inflammation
Physical Therapy Reviews 2010 VOL.15 NO.6 433
in the majority of cases, the severity of the injury
was controlled to avoid excessive haemorrhage or
damage to major blood vessels,
14,22,30,31
and is
therefore not applicable to more serious soft tissue
injuries presenting clinically. Similarly, the majority
of studies have used a muscle contusion model,
which on a mechanical, anatomical and pathological
level, is different to a stretch type muscle injury or a
ligament sprain.
The use of amputated or excised tissues samples
has obvious drawbacks, when compared to models
using perfused tissue. We must also consider that
many of the in vivo models in this area used heavy
anaesthesia on the animals throughout the experi-
ment. Anaesthesia can alter tissue perfusion by as
much as 38%,
22
which could clearly confound
findings in an inflammatory study. Furthermore, an
induced injury on an anaesthetized animal means that
the muscle will be in a relaxed state. If the muscle is
contracted at the time of contusion injury, which is
usually the case in the sporting environment, we
might expect a significantly different impact response
and force displacement.
32,33
It is clear that cryotherapy can have an effect on
key inflammatory events at a cellular and physiolo-
gical level. However, the relative benefits of these
effects have yet to be fully elucidated and it is
currently difficult to contextualize within a clinical
model. Most of the work completed to date has
focused on the animal model, perhaps due to its
relative ease with regard to obtaining tissue. We must
consider that the temperature reductions reported in
animal tissues are extremely low (intra-muscular
temperatures of 1–10uC), and usually obtained within
15 minutes of injury. These tissue temperatures are
not only difficult to replicate in a human model, but
practically, cooling is usually initiated hours or days
after injury, particularly within randomized con-
trolled studies. Notwithstanding this, there needs be
more emphasis placed on the effects of cryotherapy
on inflammation and muscle injury using a human
approach and model. Much work needs to be done
using an array of peripheral and muscle specific
markers to determine and quantify the inflammatory
process per se. Considerable new information and
knowledge within cryotherapy may be obtained by
directly examining inflammatory related markers
such as high sensitive C-reactive protein, tumour
necrosis factor alpha, nuclear factor kappa B and
interleukin molecules such as interleukin-6. In-
vestigators should also be encouraged to examine
markers of cellular oxidative stress in order to
determine the relationship between primary and
secondary free radical production (caused by soft
tissue injury) and inflammation with and without
cryotherapy application.
Considerations must also be given to the type of
soft tissue affected. Muscle, ligaments and tendon
tissue may also have different levels of tolerance when
faced with post-injury ischaemia, and some may be
more at risk of secondary cell injury and collateral
damage. We must also clarify whether the potential
benefits of cryotherapy are restricted to reducing or
preventing secondary injury in cells not initially
damaged by primary trauma, or if they could also
target retardation of primary injury progression, i.e.
rescuing cells that were involved in primary injury but
not initially destroyed.
4
This could also have con-
siderable implications for clinical management of soft
tissue injury.
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Bleakley and Davison Cryotherapy and inflammation
Physical Therapy Reviews 2010 VOL.15 NO.6 435
... However, it should be noted that NIRS does not permit direct measurement of muscle 'metabolism', rather only muscle oxygenation. A reduction in muscle metabolism could mean that surrounding tissues are more tolerant of an ischaemic environment, thus reducing the probability of secondary cell injury (Bleakley & Davison, 2010). The latter concept describes the damage that occurs following immediate muscle trauma and rapid leukocyte infiltration. ...
... Similarly it has been revealed that a higher skinfold thickness (a common measure of body fat levels) significantly increases the time required to decrease intramuscular temperature by a set amount (Otte et al., 2002). This is due to the insulation properties of adipose tissue owing to the reduced magnitude of conductive heat transfer from the body core to the external surrounding (Bleakley & Davison, 2010), therefore potentially reducing the overall effect of cold exposure. Coaches and clinical practitioners should consequently be mindful of the body compositions of athletes and patients before applying cryotherapy treatments to support recovery, performance and/or injury repair. ...
Thesis
Full-text available
Whilst Whole Body Cryotherapy (WBC) has become an emerging tool for sport and exercise recovery, its overall efficacy remains contentious. This thesis addressed a variety of issues concerning the practice. Firstly, the impact of single WBC interventions for treating exercise-induced muscle damage (EIMD) is unclear. Secondly, the influence of inter-individual factors on WBC outcomes post-exercise remains an under-investigated area. Therefore the first main study explored the effects of age and body fat content on responses to WBC following downhill running, a commonly utilised eccentric exercise model for inducing muscle damage. WBC participants underwent cryotherapy (3 minutes, −120°C) one hour post- downhill run and control (CON) participants passively recovered (20°C). Despite the presence of EIMD, WBC significantly blunted (p=0.04) the decrease in muscle torque 24 hours after the downhill run. This response was significantly influenced by age, with young participants (<40 years) retaining their muscle strength more than older participants (≥45 years). WBC may therefore attenuate EIMD and benefit muscle strength recovery following eccentrically biased exercise, particularly for young males. A subsequent downhill run study investigated the influence of WBC timing post-exercise, a factor that could clarify optimal treatment usage. An additional objective was to compare the effects of WBC with cold water immersions (CWI) since the verdict regarding which cold modality is superior for recovery remains an on-going area of controversy. It was revealed that WBC 4 hours post-exercise was ineffective in treating EIMD markers, so applying WBC within one hour after exercise may be preferable to delaying by several hours. However, WBC was no more effective than CWI, meaning that the cost vs. reward implications of WBC treatments would need further reviewing. Finally, the implications of repetitive WBC during training programmes require further evaluation due to the possibility of repetitive cold interfering with long term adaptations. The final study investigated the impact of two weekly WBC treatments on adaptations to a 6 week strength and endurance training programme. It was found that WBC participants significantly improved their muscle strength comparatively to the CON group. However WBC did not improve their jump height (p=0.23) in contrast to the CON group (p=0.01). In conclusion, repetitive WBC does not appear to blunt strength training adaptations, although there may be an interference effect in the development of explosive power.
... CWI is thought to expedite recovery from exercise by lowering skin, intramuscular and body temperature, cardiovascular strain, blood flow and increasing metabolism, blood pressure and heart rate (Bleakley and Davison, 2010b;. Although CWI does not influence glycogen resynthesis rates after exhaustive exercise in humans , other cryotherapy applications can reduce inflammatory cell infiltration after soft tissue injuries in animal studies (Bleakley and Davison, 2010a) and CWI can lower inflammatory biomarkers after contact sport (Lindsay et al., 2017) and resistance exercise in humans (Missau et al., 2018). However, there are equivocal findings that CWI does not affect muscle-specific or circulating inflammatory biomarkers after resistance exercise (Peake et al., 2017a), repeated sprints (White et al., 2014) or volleyball training in humans. ...
... CWI is thought to expedite recovery from exercise by lowering skin, intramuscular and body temperature, cardiovascular strain, blood flow and increasing metabolism, blood pressure and heart rate (Bleakley and Davison, 2010b;. Although CWI does not influence glycogen resynthesis rates after exhaustive exercise in humans , other cryotherapy applications can reduce inflammatory cell infiltration after soft tissue injuries in animal studies (Bleakley and Davison, 2010a) and CWI can lower inflammatory biomarkers after contact sport (Lindsay et al., 2017) and resistance exercise in humans (Missau et al., 2018). However, there are equivocal findings that CWI does not affect muscle-specific or circulating inflammatory biomarkers after resistance exercise (Peake et al., 2017a), repeated sprints (White et al., 2014) or volleyball training in humans. ...
... stimuli via peripheral pain receptors at the optimum threshold to induce tissue damage (Prasanth et al., 2015). Inflammation is a complicated response to protect the body from injurious agents, including microbes, physical trauma and chemical irritants clinically manifested as heat, redness, swelling and pain (Bleakley & Davison, 2011;Cássia et al., 2013). It composes series of biological and chemical reactions in the body that affects the blood vessels, immunology and different cells around the injured tissue (Ferrero-Miliani et al., 2006). ...
Article
Full-text available
Abstract Background Pain, inflammation and fever are serious conditions that are associated with various disease conditions. In modern medicine, non-steroidal anti-inflammatory drugs (NSAIDs), opioids together with corticosteroids have been considered to manage algesia and inflammation-related conditions. However, these conventional drugs are not affordable, not readily available, particularly to people living in rural areas in developing nations. Besides, they are associated with undesirable pharmacological actions. Generally, medicinal plants have been employed to manage various ailments. In Northern-Nigeria, the leaves of Culcasia angolensis (Araceae) are used traditionally to manage pain, fever and inflammation. However, scientific data validating its folkloric claim in treating pain and inflammatory-related abnormalities are not available. Hence, the current study aims to validate the antinociceptive, anti-inflammatory and antipyretic potentials of the methanol leaf extract of Culcasia angolensis (MECA). Phytochemical and acute toxicity effects of the MECA were conducted as per standard experimental procedures. The analgesic potential of the MECA was determined using abdominal writhing elicited by acetic acid and hot plate tests in mice. The actions of the MECA on acute inflammation were conducted using formalin-induced hind paw oedema and carrageenan-induced paw oedema. The Brewer's yeast-induced pyrexia was employed to check its antipyretic effect. Results The MECA inhibited abdominal writhes produced by acetic acid administration (p
... CWI is thought to expedite recovery from exercise by lowering skin, intramuscular and body temperature, cardiovascular strain, blood flow and increasing metabolism, blood pressure and heart rate (Bleakley and Davison, 2010b;Ihsan et al., 2016). Although CWI does not influence glycogen resynthesis rates after exhaustive exercise in humans (Gregson et al., 2013), other cryotherapy applications can reduce inflammatory cell infiltration after soft tissue injuries in animal studies (Bleakley and Davison, 2010a) and CWI can lower inflammatory biomarkers after contact sport (Lindsay et al., 2017) and resistance exercise in humans (Missau et al., 2018). However, there are equivocal findings that CWI does not affect muscle-specific or circulating inflammatory biomarkers after resistance exercise (Peake et al., 2017a), repeated sprints (White et al., 2014) or volleyball training (De Freitas et al., 2019) in humans. ...
... Although the physiological effects and mechanisms associated with cryotherapy in humans have been investigated (Wilcock et al. 2006;White and Wells 2013;Ihsan et al. 2016;Bongers et al. 2017) and while some advances have recently been made in the understanding of the molecular response to cryotherapy (Broatch et al. 2018), the lack of consistent and unanimous evidence has resulted in controversy over the efficacy of most cryotherapy interventions following both injury and exercise. There remains a large gap in the scientific basis for the use of cryotherapy for recovery in humans, particularly because recommendations for optimal protocols stem from evidence demonstrated in animal models (Bleakley and Davison 2010b). Evidence is specifically lacking to identify and provide guidelines concerning cryotherapy treatment application, duration, and frequency (MacAuley 2001;Bleakley et al. 2004), following both injury and exercise. ...
Article
Full-text available
Cryotherapy is utilized as a physical intervention in the treatment of injury and exercise recovery. Traditionally, ice is used in the treatment of musculoskeletal injury while cold water immersion or whole-body cryotherapy is used for recovery from exercise. In humans, the primary benefit of traditional cryotherapy is reduced pain following injury or soreness following exercise. Cryotherapy-induced reductions in metabolism, inflammation, and tissue damage have been demonstrated in animal models of muscle injury; however, comparable evidence in humans is lacking. This absence is likely due to the inadequate duration of application of traditional cryotherapy modalities. Traditional cryotherapy application must be repeated to overcome this limitation. Recently, the novel application of cooling with 15 °C phase change material (PCM), has been administered for 3-6 h with success following exercise. Although evidence suggests that chronic use of cryotherapy during resistance training blunts the anabolic training effect, recovery using PCM does not compromise acute adaptation. Therefore, following exercise, cryotherapy is indicated when rapid recovery is required between exercise bouts, as opposed to after routine training. Ultimately, the effectiveness of cryotherapy as a recovery modality is dependent upon its ability to maintain a reduction in muscle temperature and on the timing of treatment with respect to when the injury occurred, or the exercise ceased. Therefore, to limit the proliferation of secondary tissue damage that occurs in the hours after an injury or a strenuous exercise bout, it is imperative that cryotherapy be applied in abundance within the first few hours of structural damage.
... Weitere positive Effekte lassen sich auf die Reduktion der Zellapoptose sowie auf die Aktivität der weißen Blutkörperchen innerhalb des Gefäßsystems zurückführen, die durch den "oxidativen Burst" (Bildung von Sauerstoffradikalen) einen negativen Einfluss auf die Wundheilung haben können. Somit kann das Gewebe vor sekundärer Zellschädigung und dem Zelltod potenziell geschützt werden [5]. ...
Article
Behandlungsparadigmen sollten in der Sportphysiotherapie regelmäßig aktualisiert werden, basierend auf dem aktuellen Stand der Forschungsergebnisse. Das gilt insbesondere auch für den Einsatz von Kälte im Sport.
Article
Zusammenfassung Mit menschheitsgeschichtlich langer Tradition findet die Kryotherapie auch in der heutigen Zeit Anwendung gegen chronische und akute Schmerzen. Im Sportkontext wird Kälte überdies zur Regenerations- und Leistungsverbesserung im Sport eingesetzt. Zu gängigen Anwendungsformen in der Physiotherapie gehören beispielsweise Eislolli, Eispackungen, Eisspray und die Kältekammer. Den maßgeblichen Unterschied in der Anwendung bildet die Anwendungsdauer, die je nach direkter oder indirekter Kälte und den Temperaturunterschieden variiert. Dieser Artikel soll einen Einblick in die bekannten Wirkmechanismen und Behandlungsmöglichkeiten geben.
Chapter
Physical activity results in a series of proinflammatory reactions and innate immune responses, which occur postexercise. This is followed by antiinflammatory reactions that are critical for regeneration and healing. The severity of inflammation following exercise depends on the type, duration, and intensity of the exercise bout, as well as the training status of the individual. Interventions designed to reduce the inflammatory response following exercise may, in fact, be detrimental to adaptation, though they may positively impact performance and competition with short turnaround times. Although acute inflammation is critical for recovery, chronic inflammation—even low-grade systemic and tissue-specific simmering inflammation—appears to be a mechanism associated with the aging process and is related to many chronic diseases. It appears that regular, sustained physical activity, including endurance and resistance-type exercise, may provide a protective impact on chronic low-grade inflammatory conditions. General patterns of dietary intake and specific nutrients and other dietary constituents or supplements demonstrate promise for positively impacting this relationship. Many of the same cytokine and chemokine actors that are modulated by physical activity also are affected by diet. Many of the intercellular signaling systems modulated by physical activity are also regulated by various aspects of nutrition, including carbohydrate and fatty acid metabolism and oxidation. While much of the focus of this chapter is on exercise training among people at optimal ages for fitness, there are important and obvious implications for nonathletes across the lifespan, especially during childhood and among the elderly. Research into non-steroidal anti-inflammatory drugs also has implications for exploring the effect of diet in modulating inflammatory and immune responses in context of physical activity.
Article
Objectives Resources of heat or cold therapies have been widely used for their low cost, analgesic action and for assisting the rehabilitation of acute or chronic injuries. The objective of this study was to search for associations between skin surface temperature and pressure pain tolerance thresholds (PPTs) of healthy individuals undergoing cryotherapy and thermotherapy. Methods This is an experimental clinical trial with 22 healthy university students aged between 18 and 35 years. Volunteers underwent thermography and algometry assessments at 6 points in both knees before, immediately after, and 20 minutes after the application of frozen (cryotherapy) or heated (thermotherapy) gel bags in the right knee for 20 minutes. Data were analyzed by 1-way analysis of variance, Student's t test, and Pearson or Spearman correlation tests. Results There was a significant change in skin surface temperature after cryotherapy and thermotherapy, which was maintained after 20 minutes of withdrawal (P < .001). After the intervention, no significant differences were observed regarding the PPT compared to the baseline measurements, nor between the experimental and control knees. Conclusion Cryotherapy and thermotherapy produced significant changes in the temperature of the evaluated points after their application. Despite this, no differences in pain tolerance were observed, and there was little association between skin surface temperature and PPT in the knees of healthy women after application of the resources.
Article
Background: Surface cooling is frequently used in a number of conditions, especially traumatic, ischemic, burn, and neurologic injury to reduce the tissue damage. However, the protective mechanisms of cold therapy on traumatized tissues remain unclear. Tumor necrosis factor-α (TNF-α) is a fundamental mediator in inflammatory reactions and trauma-induced tissue injury. In the present study, we examined the microvascular response to TNF-α challenge and the effects of local cooling on the TNF-α–induced changes in the striated muscle of hamsters. Methods: By the use of the dorsal skinfold chamber preparation and in vivo fluorescence microscopy in combination with computer-based image analysis, we determined TNF-α–induced leukocyte rolling and adhesion to microvascular endothelium, capillary perfusion, venular leakage,and cellular apoptosis with and without surface cooling. Results: We found that topical administration of 2000 units TNF-α caused a progressive impairment of microvascular perfusion and increased leukocyte recruitment and vascular macromolecular leakage. Local cooling to 10°C for 60 minutes markedly (P < .05) inhibited the TNF-α–induced capillary perfusion failure and leukocyte response and slightly attenuated the increase of microvascular permeability after 180 minutes of stimulation. Furthermore, it was observed that 24 hours of TNF-α stimulation increased the number of apoptotic cells (ie, nuclear condensation and fragmentation) by 10-fold. This TNF-α–mediated effect was almost abolished by treatment with local hypothermia. Conclusion: These data suggest that the protective effect of surface cooling of traumatized tissue is due to its attenuation of the microvascular inflammatory response associated with the inhibition of the process of apoptosis. (Surgery 1999:126:881-9.)
Article
This preliminary report describes the use of a rat model developed to study in vivo the effect of anesthesia, contusion, and cryotherapy on skeletal muscle microcirculation by use of an implanted chamber. The diameters of arterioles and venules within the chamber were determined by photomicroscopy in the contusion study and by compound videomicroscopy in the anesthesia study; microvascular perfusion was determined by laser Doppler fluxmetry (LDF). Combined ketamine and xylazine anesthesia significantly reduced (P < 0.05) arteriolar and venular diameters by 32.4% and 37.8%, respectively, and average LDF measurements by 36.1%. Contusion significantly increased arteriolar diameters over baseline values (P < 0.05); cryotherapy did not alter arteriolar diameters but increased venular diameters (P < 0.05). It is hypothesized that this increase in venular diameter may, by increasing the surface area available for reabsorption, explain one mechanism by which cryotherapy decreases the edema of contusion. Use of this model should help to advance the understanding of microcirculatory dynamics following contusion and cryotherapy. © 1993 Wiley-Liss Inc.
Article
The effects of early cryotherapy on healing of rat gastrocnemius muscle injury were investigated in schedules similar to those in clinical use. After the treatment: (1) hematoma between ruptured myofiber stumps was smaller and (2) extravasation of inflammatory cells to the injury site and (3) activation of satellite cells to myotubes and mature myofibers were delayed. Early proliferation of granulation tissue was not altered. Thus, cryotherapy affected the time-table of the healing process rather than causing qualitative differences. No negative side effects of cryotherapy were found. Positive effects of cryotherapy in clinical practice most likely depend on factors other than those involved with actual regeneration of the muscle lesion, such as reducing muscle spasms, which can cause reruptures, and analgesia allowing early mobilization. The results support the current clinical practice of treating acute muscle fiber ruptures with initial cold application followed by active early mobilization.
Article
The effect of combined cryotherapy/compression versus cryotherapy alone on the Achilles tendon is undetermined. Standardized combined cryotherapy/compression changes in midportion Achilles tendon microcirculation are superior to those with cryotherapy during intermittent application. Controlled laboratory study. Sixty volunteers were randomized for either combined cryotherapy/compression (Cryo/Cuff, DJO Inc, Vista, California: n = 30; 32 +/- 11 years) or cryotherapy alone (KoldBlue, TLP Industries, Kent, United Kingdom: n = 30; 33 +/- 12 years) with intermittent 3 x 10-minute application. Midportion Achilles tendon microcirculation was determined (O2C, LEA Medizintechnik, Giessen, Germany). Both Cryo/Cuff and KoldBlue significantly reduced superficial and deep capillary tendon blood flow within the first minute of application (43 +/- 46 arbitrary units [AU] vs 10 +/- 19 AU and 42 +/- 46 AU vs 12 +/- 10 AU; P = .0001) without a significant difference throughout all 3 applications. However, during recovery, superficial and deep capillary blood flow was reestablished significantly faster using Cryo/Cuff (P = .023). Tendon oxygen saturation was reduced in both groups significantly (3 minutes Cryo/Cuff: 36% +/- 20% vs 16% +/- 15%; KoldBlue: 42% +/- 19% vs 28% +/- 20%; P < .05) with significantly stronger effects using Cryo/Cuff (P = .014). Cryo/Cuff led to significantly higher tendon oxygenation (Cryo/Cuff: 62% +/- 28% vs baseline 36% +/- 20%; P = .0001) in superficial and deep tissue (Cryo/Cuff: 73% +/- 14% vs baseline 65% +/- 17%; P = .0001) compared with KoldBlue during all recoveries. Postcapillary venous filling pressures were significantly reduced in both groups during application; however, Cryo/Cuff led to significantly, but marginally, lower pressures (Cryo/Cuff: 41 +/- 7 AU vs baseline 51 +/- 13 AU; P = .0001 and KoldBlue: 46 +/- 7 AU vs baseline 56 +/- 11 AU; P = .026 for Cryo/Cuff vs KoldBlue). Increased tendon oxygenation is achieved as tendon preconditioning by combined cryotherapy and compression with significantly increased tendon oxygen saturation during recovery in contrast to cryotherapy alone. Both regimens lead to a significant amelioration of tendinous venous outflow. Combined cryotherapy and compression is superior to cryotherapy alone regarding the Achilles tendon microcirculation. Further studies in tendinopathy and tendon rehabilitation are warranted to elucidate its value regarding functional issues.
Article
The most common treatment of soft tissue contusions is ice application (cryotherapy). The physiological basis for this therapy is assumed to be cold-mediated vasoconstriction resulting in decreased edema formation and a reduction in overall morbidity. This proposed mechanism has not been tested. The present research examined the hypothesis that cryotherapy following contusion is effective because it reduces microvascular perfusion and subsequent edema formation. The microcirculatory responses to contusion were studied with and without cryotherapy in a chronically instrumented rat model. Initial studies evaluated the immediate effects of cryotherapy on arteriolar and venular diameters and microvascular perfusion (using laser Doppler floxmetry). Variables were measured before and immediately after 20 minutes of cryotherapy. Two additional studies monitored the same microvascular parameters longitudinally in four sets of chronically instrumented animals. Groups of rats studied had contusion or sham contusion with ice treatment or no ice treatment. Measurements were performed repeatedly before and after treatment for 24 hours or 96 hours after contusion/sham contusion. The acute microvascular effects of cryotherapy were vasoconstriction and decreased perfusion. However, when cryotherapy was used as a treatment following contusion/sham contusion, there were no long-lasting microvascular effects of cryotherapy either in the presence or absence of contusion. These results indicate that cryotherapy of striated muscle following contusion does not reduce microvascular diameters or decrease microvascular perfusion. Alternate mechanisms of action for cryotherapy treatment need to be investigated.
Article
Of all tissues of the extremities, muscle is the least tolerant of ischemia. Hypothermia of tissue is considered beneficial for the maintenance of viability of muscle in amputated limbs before surgical replantation, but it has never been established that conventional cooling in an ice bath or its equivalent (temperature of tissue, approximately 1 degree Celsius) is the optimum level of hypothermia for minimizing metabolic derangement in ischemic muscle. In this study, we first defined the time course and level of metabolic derangement of muscle in twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree Celsius. The levels of adenosine triphosphate and phosphocreatine and the mean intracellular pH of the muscles in the lateral aspect of the thigh in each limb were monitored with phosphorus nuclear magnetic-resonance spectroscopy over time. The excised muscles from six freshly amputated legs of live humans were then similarly studied to determine whether muscles from cats and from humans exhibit comparable bioenergetic responses to hypothermic ischemia. A final series of ten ischemic hind limbs from cats was studied by nuclear magnetic resonance and muscle biopsy for direct biochemical assay of tissue energy metabolites to compare the metabolic benefits of two different methods of preserving limbs: continuous cooling in an ice bath, and a newly devised protocol for the rapid induction and maintenance of so-called intermediate (10 +/- 5 degrees Celsius) hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a paradoxical metabolic response to extreme cold (1 degree Celsius). The rate of metabolic deterioration progressively declined with decreasing temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius, no additional benefit was detected, and at 1 degree Celsius, there was a significant acceleration in the rates of degradation of adenosine triphosphate and phosphocreatine and in the production of lactate. The rate of degradation of adenosine triphosphate in human ischemic muscle was also faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical response is apparently due to a severe inhibition of the calcium pump of the sarcoplasmic reticulum of the muscle cell at temperatures of less than 5 degrees Celsius. The inhibition permits an efflux of calcium to the myofibrils, which stimulates both glycolysis and the degradation of adenosine triphosphate by myofibrillar adenosine triphosphatase.
Article
Free radicals are chemical species with one or more unpaired electrons in their outer orbital. Their production is essential to normal metabolism but they are theoretically destructive unless tightly controlled. We review the chemistry of free radical production and the intra/extracellular defence systems that limit their toxicity. Particular reference is made to biochemical processes which we believe are relevant to maintaining an inflammatory reaction. As a clinical illustration we describe mechanisms pertinent to the perpetuation of the chronic inflammation of rheumatoid synovitis.
Article
We compared the biomechanical properties of passive and stimulated muscle rapidly lengthened to failure in an experimental animal model. The mechanical param eters compared were force to tear, change in length to tear, site of failure, and energy absorbed by the muscle- tendon unit before failure. Paired comparisons were made between 1) muscles stimulated at 64 Hz (tetanic stimulation) and passive (no stimulation) muscles, 2) muscles stimulated at 16 Hz (wave-summated stimu lation) and passive muscles, and 3) muscles stimulated at 64 Hz and at 16 Hz. Both tetanically stimulated and wave-summation con tracted muscles required a greater force to tear (at 64 Hz, 12.86 N more, P < 0.0004; and at 16 Hz, 17.79 N more, P < 0.003) than their nonstimulated controls, while there was no statistical difference in failure force between muscles stimulated at 16 Hz and 64 Hz. The energy absorbed was statistically greater for the stim ulated muscles than for the passive muscles in Groups 1 and 2 (at 64 Hz, 100% more, P < 0.0003; and 16 Hz, 88% more, P < 0.0002). In Group 3, the tetanically contracted muscle-tendon units absorbed 18% more energy than the wave-summated stimulated muscles (P < 0.01). All muscles tore at the distal musculotendi nous junction, and there was no difference in the length increase at tear between muscles in each group. These findings may lead to enhanced understanding of the mechanism and physiology of muscle strain injuries.