Stikkordarkiv: Stress

A CLASSIFICATION-BASED COGNITIVE FUNCTIONAL APPROACH FOR THE MANAGEMENT OF BACK PAIN

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Denne beskriver et ganske så komplett opplegg for behandling og undervisning av klienter med nesten alle typer muskel og leddplager.

Klikk for å få tilgang til OSullivanIFOMPT-Oct2012.pdf

Pathoanatomical factors: F.eks. funn på røntgen og MRI, som spiller liten rolle i kroniske muskel og leddplager.

Physical factors: muskelspenning og bevegelsesmønster endres ved smertetilstander. F.eks. kjermuskulatur spenner seg mer i bevegelser hos smertepasienter.

Lifestyle factors: interessant at mat og kosthold er det eneste av livsstilsfaktorer som ikke nevnes på denne listen. Ellers er trening, stress, søvn, røyk, overvekt, m.m. med.

Cognitive and psychosocial factors: angst, depresjon, frykt, katastrofering, og særlig ideen om at (f.eks.) ryggen må beskyttes pga smertene.

Social factors: trivsel i jobb, familie, forhold, og livssituasjon.

Neurophysiological factors: endringer i hjernen, som f.eks. mindre går materie, økt hjerneaktivitet i hvile, endres kroppsbilde, mindre nedregulering av smerte.

Individual factors: mål med behandling, forventninger, grunnleggende helsekunnskap, m.m.

Genetic factors: Visse gener gir økt disponering for smertetilstander.

Jeg likte spesielt dette sitatet:

Manual therapy is only used as a window of opportunity to change behaviors where movement impairments are present.

Structure and Biomechanics of Peripheral Nerves: Nerve Responses to Physical Stresses and Implications for Physical Therapist Practice

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Nevner det aller meste om perifere nerver og hvordan de får plager av «normale» sitasjoner, som f.eks. musearm.

http://www.ncbi.nlm.nih.gov/pubmed/16386065

http://ptjournal.apta.org/content/86/1/92.long

Abstract

The structural organization of peripheral nerves enables them to function while tolerating and adapting to stresses placed upon them by postures and movements of the trunk, head, and limbs. They are exposed to combinations of tensile, shear, and compressive stresses that result in nerve excursion, strain, and transverse contraction. The purpose of this appraisal is to review the structural and biomechanical modifications seen in peripheral nerves exposed to various levels of physical stress. We have followed the primary tenet of the Physical Stress Theory presented by Mueller and Maluf (2002), specifically, that the level of physical stress placed upon biological tissue determines the adaptive response of the tissue. A thorough understanding of the biomechanical properties of normal and injured nerves and the stresses placed upon them in daily activities will help guide physical therapists in making diagnoses and decisions regarding interventions.

Figure 1.

Structural components of peripheral nerves. In the endoneurial compartment (En), a single Schwann cell envelops several unmyelinated axons, and another Schwann cell provides multiple wrappings of plasma membrane forming the myelin sheath of a myelinated axon. The portion of a myelinated axon myelinated by a single Schwann cell is called the internode, and internodes are separated by nodes of Ranvier. Schwann cells associated with both unmyelinated and myelinated axons are covered with a continuous basal lamina (BL). Capillaries (Cap) are present within the endoneurial compartment, and collagen fibers (Col) run primarily longitudinally between the axons. The axons, Schwann cells, collagen, and endoneurial fluid are bundled into a fascicle by the perineurium (Pe). The perineurium consists of several layers of flattened perineurial cells connected by tight junctions and covered internally and externally by a basal lamina. The layers of perineurial cells are separated by collagen fibers (Col) oriented obliquely. Several fascicles are bundled together by the epineurium (Ep) to form a nerve. The epineurium consists primarily of fibroblasts, collagen fibers (Col), and elastic fibers. The epineurium between fascicles is termed the interfascicular epineurium, and that encompassing all of the fascicles is termed the epifascicular epineurium. Arterioles (A) and veins are oriented primarily longitudinally within the epineurium.

Blood supply

The blood supply to nerves is provided by coiled segmental arteries that enter the epineurium periodically along the length of the nerve and form the vasa nervorum. Arteries divide into epineurial arterioles that form an anastomotic network running primarily longitudinally within the epifascicular epineurium and the interfascicular epineurium (Fig. 3). Epineurial arterioles are supplied with a perivascular plexus of serotoninergic, adrenergic, and peptidergic nerves.17,18 Perforating arterioles cross the perineurium at oblique angles and carry a short sleeve of perineurial cells into the fascicle.3,19 Perineurial arterioles have poorly developed smooth muscle and thus have limited ability to regulate intrafascicular blood flow.20 Within the endoneurium, arterioles immediately turn into large-diameter, longitudinally oriented capillaries that allow blood flow in either direction (Fig. 3).21 The endothelial cells of endoneurial capillaries are connected by tight junctions, thus forming the tight blood-nerve barrier.7 Venules return blood to the venous system. Of note, lymphatic capillaries are present only within the epineurium; there is no lymphatic drainage from the intrafascicular or endoneurial space.22

Biomechanical properties

Under normal physiological conditions imposed by posture and movement, nerves are exposed to various mechanical stresses. Stress is defined as force divided by the area over which it acts9,23–25 and can be applied to a nerve as tensile, compressive, or shear stress or as a combination of stresses (Fig. 4). Tensile stress may be applied to tissues either parallel or perpendicular to the length of the nerve, causing respective longitudinal or transverse stress in the nerve. When joint motion causes elongation of the nerve bed, the nerve is inherently placed under tensile stress and accommodates the stress by both elongating and gliding.15 The deformation or change in nerve length induced by longitudinal tensile stress is called strain and is expressed typically as percent elongation.23,26–28 Displacement or gliding of a nerve relative to the surrounding nerve bed is called excursion.29–31 The direction of excursion may be longitudinal or transverse, or both, relative to the nerve tract31,32 and is measured in millimeters.

Figure 4.

Physical stresses placed on peripheral nerve. Tensile stress applied longitudinally to peripheral nerve creates an elongation of the nerve (an increase in strain). The transverse contraction that occurs during this elongation is greatest at the middle of the section undergoing tensile stress.

When the nerve bed is elongated, the nerve is placed under increased tensile stress. With the elongation of the nerve bed, the nerve glides toward the moving joint,1,33,34 a movement termed convergence.1 Conversely, if the nerve bed tension is relieved during joint motion, the nerve will realign along the shortened nerve bed by gliding away from the moving joint, a movement termed divergence.33 Convergence in the median nerve may be demonstrated during elbow extension (Fig. 5). The motion elongates the bed of the median nerve, causing the nerve segment in the arm to glide distally toward the elbow and the nerve segment in the forearm to glide proxi mally toward the elbow. In contrast, elbow extension relieves the tensile stresses in the ulnar nerve bed, causing the ulnar nerve to diverge away from the elbow (Fig. 5).

Figure 5.

Excursion of the median nerve (solid line) and the ulnar nerve (dotted line) during elbow extension followed by wrist extension. The concepts of nerve convergence toward and divergence away from a moving joint are illustrated in measurements of excursion taken at each site indicated. All measurements are reported in millimeters of proximal (P) or distal (D) excursion. The direction of excursion is also represented by solid arrows for median nerve excursion and open arrows for ulnar nerve excursion. (A) With elbow extension from 90° of flexion to 0° of flexion, the median nerve bed lengthens and the median nerve glides toward the elbow (converges). With the same joint motion, the ulnar nerve bed shortens and the ulnar nerve glides away from the elbow (diverges). (B) With wrist extension from 0° of extension to 60° of extension, both nerve beds lengthen; thus, both nerves converge toward the wrist. The magnitude of excursion is greatest closest to the moving joint. Data were obtained from: aDilley et al,29 bWright et al,27 and cWright et al.33 Measurements of nerve excursion at the wrist and elbow in panel A were extrapolated from studies of nerve excursion during elbow flexion from 0° to 90°.27

Nerve Stiffness

First, a recent study43 measured greater nerve compliance in nerve segments that cross joints than in segments that do not cross joints.

Second, nerve stiffness is greater in long nerve sections and in nerve sections with numerous branches.15 Severing nerve branches or vessels but leaving the nerve in situ results in increased compliance and decreased stiffness.15

Third, nerve stiffness is greater when a nerve is elongated rapidly rather than slowly. In addition, the ultimate strain at the point of failure appears to be dependent on the rate of elongation.

When a nerve is placed under tension and maintained at that new fixed length over time, there is a reduction in the tension in the nerve or the force required to maintain the fixed length. The observed reduction in tension may be plotted in a stress-relaxation curve (Fig.8).25,44 The majority of relaxation occurs in the first 20 minutes of fixed elongation.25,44Stress relaxation in nerves that are stretched slowly is greater than in nerves that are stretched rapidly.25,37,44–46 This phenomenon was observed when comparisons were made for rabbit tibial nerves stretched at different rates to lengths 6% longer than their resting lengths. Over the 60-minute relaxation time, there was a 57% reduction in stress in nerves elongated at 0.08% per second,45 but only a 34% reduction in stress in nerves elongated at 3.0% per second.44

Figure 8.

Stress-relaxation curve demonstrating viscoelastic properties of peripheral nerve. When a nerve is elongated and the new length is kept constant, there is a rapid reduction in the stress within the nerve, expressed as percent reduced relaxation. Most of the relaxation occurs in the first 20 minutes. The degree of elongation affects the amount of stress relaxation that will occur. The dotted line represents a nerve that has been elongated to 6% above its resting length. The solid line represents nerves that have been elongated to 9% and 12% above their resting lengths. Greater stress relaxation was documented in nerves that underwent less elongation.25,44 Modified from Kwan MK, Wall EJ, Massie J, Garfin SR. Strain, stress, and stretch of peripheral nerve: rabbit experiments in vitro and in vivo. Acta Orthop Scand. 1992;63:267–272, with permission of Taylor and Francis AS.

However, a nerve stretched repetitively to 8% or 10% strain exhibits a reduced slope of the stress-strain curve, indicating that that nerve undergoes less stress with successive elongations because of increased compliance and decreased stiffness.

Compression of nerve

In addition to tensile stress, nerves are exposed statically and dynamically to compressive stresses. As mentioned previously, the laws of physics dictate that the cross-sectional area of a cylindrical object is reduced as the cylinder is elongated. As a nerve is elongated under tensile force, the nerve undergoes transverse contraction, which is resisted by the fluid and nerve tissue contained within the connective tissue sheath.15,39The magnitude of the transverse contraction stress is greatest at the center of the elongating segment15 (Fig. 4). Nerves also may be compressed externally by approximation to adjacent tissues, such as muscle, tendon, or bone, or by pressure increases in the extraneural environment. Compression of a nerve segment causes displacement of its internal contents in transverse and longitudinal directions. As shown in rat nerve, extraneural compression causes an immediate displacement of endoneurial fluid to the edges of a compressive cuff over 5 to 10 minutes and a much slower displacement of axonal cytoplasm over the course of hours.48 The damage to axons and myelin is greatest at the edges of the compressed zone,48,49 where the shear forces are highest.50

At the edges of the cuff, however, myelin retraction with resultant widening of nodes and paranodal demyelination occurred. These structural alterations in myelin may be expected to result minimally in impaired impulse conduction or maximally in demyelination and a conduction block.

In response to biomechanical stresses placed on a nerve as an individual assumes a posture or movement, the nerve follows the path of least resistance.29 Combinations of tensile, shear, and compressive stresses result in combinations of nerve excursion, strain, and transverse contraction. Because the biomechanical forces on the nerve are so intricately linked, the sequencing and range of joint movement affect the magnitude and direction of excursion,27,29 the magnitude of nerve strain,27,29,35 and the degree of transverse contraction at different sites along the nerve.27

Simultaneous nerve excursion, strain, and transverse contraction may be seen in the ulnar nerve as an example of responses to physical stresses imposed during movements of the upper limb. When the upper limb is maintained in a position of 90 degrees of shoulder abduction and 90 degrees of shoulder external rotation with the wrist neutral, and when the elbow is moved from 90 degrees of flexion to full extension, the ulnar nerve bed is shortened and the tensile stress on the nerve is decreased. With this motion, there is divergence of the ulnar nerve away from the elbow (Fig. 5), decreased nerve strain, especially at the elbow (Fig. 6), and decreased compression within the cubital tunnel.27,29,33 When the wrist then is extended from neutral to full extension, the ulnar nerve bed is lengthened, resulting in convergence of the nerve toward the wrist (Fig. 5), an increase in nerve strain (Fig. 6), and transverse contraction greatest in the nerve segment across the carpal bones and at the tunnel of Guyon.27,29,33 The magnitude of nerve strain and excursion will be greatest near the wrist, and the fascicles will rearrange as the nerve assumes a flattened oval shape. Because the nerve does not lie directly on the rotational axis of joint motion, the fascicles farthest from the axis will undergo greater strain than those closer to the center of rotation51

Figure 6.

Strain of the median nerve (solid line) and the ulnar nerve (dotted line) during elbow extension followed by wrist extension. Measurements at the sites indicated are reported as percent increase (↑) or percent decrease (↓) in strain. (A) With elbow extension from 90° of flexion to 0° of flexion, median nerve strain increases because of elongation of the nerve bed. Conversely, ulnar nerve strain decreases as the ulnar nerve bed shortens. (B) With wrist extension from 0° of extension to 60° of extension, the strain at the sites measured increases in both nerves as both nerve beds elongate. The magnitude of the strain is greatest closest to the moving joint. Data were obtained from: aWright et al27and bWright et al.33 Measurements of nerve excursion at the wrist and elbow in panel A were extrapolated from studies of nerve excursion during elbow flexion from 0° to 90°.27

Continuum of physical stress states

First, levels of physical stress lower than the levels required for tissue maintenance (low stress) result in a reduced ability of the tissue to tolerate subsequent stress and are consistent with tissue plasticity and response to functional demand.

Second, levels of physical stress in the range required for tissue maintenance (normal stress) result in no tissue adaptations and are considered to maintain a state of equilibrium.

Third, physical stress levels that exceed the range required for tissue maintenance (high stress) result in an increase in the tolerance of the tissue for stress in an effort to meet the mechanical demand.

Fourth, physical stress levels that exceed the capacity of some components of the tissue (excessive stress) result in tissue injury.

Fifth, levels of physical stress that are extreme (extreme stress) result in tissue death.

Finally, it is important to note that the physical stress level is a composite value with variable components of magnitude, time, and direction or type of stress.

 In the functional zone, the physical stresses on the nerve are sufficient to maintain a state of equilibrium and normal physiological function. In the dysfunctional zone, various levels of physical stress have altered the ability of the nerve to tolerate subsequent stress.

Figure 9.

Continuum of physical stress states. The white area represents the functional zone in which the physical stresses on the nerve are sufficient to maintain a state of equilibrium and normal physiological function. The shaded areas represent dysfunctional zones resulting from various levels of physical stress placed on the nerve tissue. Under conditions of prolonged low stress, the functional zone will shrink in width and shift to the left, reducing the ability of the tissue to tolerate subsequent stresses even of previously normal levels. Under conditions of high stress, the functional zone may expand and shift to the right, improving the ability of the tissue to tolerate subsequent physical stress. If the nerve is exposed to prolonged or repeated excessive stress, the functional zone will shrink in width. Although scarring of damaged tissue may enable the nerve to tolerate subsequent physical stresses, the physiological function of the nerve will be reduced. Exposure to extreme stress will result in disruption of axon continuity or neural cell death and significantly reduced physiological function.

Immobilization Stresses

Under conditions of immobilization, such as casting, splinting, and bracing, peripheral nerves are exposed to levels of physical stress that are lower than those necessary to maintain the nerves in a state of equilibrium or in a functional zone (Fig. 9). According to the Physical Stress Theory, nerve will undergo predictable physiological and structural modifications proportional to the levels of reduced stress and the duration of immobilization.2 Immobilization induces cell biological changes in axons and axon terminals52–54 and structural changes in myelin and nerve connective tissue layers that likely alter the ability of nerves to tolerate subsequent physical stress.

We hypothesize that after a period of immobilization, the width of the functional zone on the continuum of physical stress states will shrink and shift toward the left (Fig. 9).

Lengthening Stresses

Nerves are exposed to various levels of longitudinal tensile stress during limb-lengthening procedures, such as distraction osteogenesis (Ilizarov procedures), traction injuries, and stretching maneuvers. The tissue response is dependent upon the magnitude and duration of the tensile stress. The extant data indicate that lengthening of 6% to 8% for a short duration causes transient physiological changes that appear to be within the normal stress tolerance of the tissue, whereas acute strains of 11% and greater cause long-term damage and may be considered to be excessive or extreme stress states.

In cadavers, positioning in shoulder depression, 90 degrees of shoulder abduction, 90 degrees of shoulder external rotation, 70 degrees of forearm supination, 60 degrees of wrist extension, full finger extension, and full elbow extension resulted in 7.6%±8.2% (X̄±SD) strain in the median nerve measured just proximal to the wrist.28 Adults who were healthy and who were placed in this same position lacked 12±13 degrees (X̄±SD) of elbow extension because of substantial discomfort in the limb.61 The subjects reported pain of 5.1±1.9 (X̄±SD) on a 10-point visual analog scale, and 36% of the subjects reported paresthesia in the upper limb. Taken together, these findings suggest that many people are unable to tolerate levels of strain below the theoretical 11% threshold.

Compression Stresses

Compression on a nerve may be the result of extraneural force or may occur as transverse contraction secondary to increased longitudinal strain (Fig. 4). Compression stress of a low magnitude and a short duration may result in reversible physiological and minor structural changes. Compressive stress of a high magnitude, however, may result in structural alterations in myelin sheaths and even disruption of axons. Low-magnitude compressive stress applied over a long period of time may cause significant structural changes in the nerve secondary to impairment of blood flow and sequelae of ischemia.

As with strain-induced injury, a threshold for compression-induced nerve injury is difficult to determine. Common functional positions may result in compression pressures that approach or exceed the 20 to 30 mm Hg demonstrated to impair nerve blood flow.75 The carpal tunnel is a site well known for compressive damage to the median nerve and thus has been well studied. Carpal tunnel pressure in subjects who were healthy was measured at 3 to 5 mm Hg with the wrist in a neutral position.76–78 Simply placing the hand on a computer mouse was shown to increase the tunnel pressure from the resting 5 mm Hg to 16 to 21 mm Hg,79 and actively using the mouse to point and click increased the tunnel pressure to 28 to 33 mm Hg, a pressure high enough to reduce nerve blood flow.

In subjects with carpal tunnel syndrome, pressure in the carpal tunnel was 32 mm Hg with the wrist in a neutral position and rose to a mean of 110 mm Hg with full wrist extension in subjects with carpal tunnel syndrome.76 These tunnel pressures exceed the threshold of 20 to 30 mm Hg for vascular perfusion even at rest. Taken together, these findings suggest that even functional positions, such as the use of a computer keyboard and mouse, place the wrist in a position of increased carpal tunnel pressure, compromising nerve blood flow and placing people at risk for median nerve injury.

Direct damage to myelin and axons has been shown to occur with extraneural compression of as low as 50 mm Hg maintained for 2 minutes,48 and the percentage of damaged fibers increases with increasing force. Ten days after the application of compressive stress at 50 mm Hg, 30% of the axons in the region under the compressive cuff showed evidence of demyelination, focal myelin thickening, remyelination, and axonal degeneration or regeneration.48

The pathological consequences of prolonged compression include subperineurial edema; inflammation; deposition of fibrin; activation of endoneurial fibroblasts, mast cells, and macrophages; demyelination; axon degeneration; and fibrosis.83 Compression of a very long duration has been modeled in animals with loose ligatures,88 Silastic* tubes,89,90and pressure balloons placed within an anatomical tunnel.91 The pathological findings are thought to result from both inflammatory and cellular phenomena and include changes in the blood-nerve barrier, thickening of the perineurium and epineurium, thinning of myelin, demyelination and degeneration of axons in the fascicle periphery, and slowed nerve conduction velocity.

In the case of chronic compression, decompression is paramount. Physical therapy intervention should focus on reduction of inflammation, improvement in blood flow, and enhancement of the capacity of the nerve for strain and excursion along its full length in an effort to reduce the physical stress on the compressed region.

Repetitive Stresses

Vibration constitutes one form of repetitive stress. We know from studies of humans who use hand-held vibrating tools that vibration stresses can cause reductions in tactile sensation, as well as other sensory disturbances96 and reduced grip force.97,98Furthermore, myelin breakdown and fibrosis have been seen in the dorsal interosseous nerve at the wrist in people with vibration-induced neuropathy.99 Long-term exposure to vibration stresses has been shown to result in the grouping of muscle fiber types in muscle biopsies, indicative of denervation and reinnervation.98

Repetitive movements, such as those that occur in work-related musculoskeletal disorders, were discussed in detail recently by Barr and Barbe.102 The stresses placed upon the tissues may be variable in terms of type, magnitude, frequency, and duration, and the combination of these factors may place nerves in normal to extreme levels of physical stress. The chronic inflammation associated with repetitive movements places nerves under constantly higher hydrostatic compressive stress, which may increase further with contraction of the surrounding muscles. Chronic inflammation elicits within the nerves a remodeling response that seeks to add mechanical stability.103 The most common outcome is the deposition of collagen in the connective tissue layers, which leads to decreased compliance of the nerves to elongation. As with chronic compression, the approach for assessment and treatment of injuries attributable to repetitive movements must address the chronic inflammatory state and connective tissue changes. Of primary importance in interventions for all stress-induced injuries are the identification and characterization of physical stresses and the modification of their components, magnitude, time, and direction, as outlined in the physical stress theory.2

Summary

This assessment should guide treatment interventions to normalize the stresses on the nerves, be they rest, soft tissue or neurodynamic mobilization, stretching, modalities, exercise, or patient education. Treatment rationale should be based on an educated understanding of the biomechanical properties of normal and pathological nerves. The concept of a continuum of low-normal-high-excessive-extreme stresses may be used as a training tool for patient education, pointing out examples of daily activities that fall under the different categories.

Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries

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Denne viser hvordan CO2-responsen er litt forskjellige i forskjellige blodkar. Den er sterkere i blodkar inni hjernen enn i blodkar i kraniet, ansiktet og ryggraden. Blodkar i ryggraden har større respons enn blodkar i ansiktet, men mindre respons enn blodkar i hjernen.

http://jp.physoc.org/content/590/14/3277.long

Because of methodological limitations, almost all previous studies have evaluated the response of mean blood flow velocity (Vmean) in the middle cerebral artery (MCA) to changes in CO2 as a measure of CO2 reactivity across the whole brain (Aaslid et al. 1989; Ainslie & Duffin, 2009; Ainslie & Ogoh, 2009).

 

ICA, VA and BA CO2 reactivity was significantly higher during hypercapnia than during hypocapnia (ICA, P < 0.01; VA, P < 0.05; BA, P < 0.05), but ECA and MCA were not significantly different.

The major finding from the present study was that cerebral CO2 reactivity was significantly lower in the VA and its distal artery (BA) than in the ICA and its distal artery (MCA). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation. Our second major finding was that ECA blood flow was unresponsive to hypocapnia and hypercapnia, suggesting that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation. These findings suggest that different CO2 reactivity may explain differences in CBF responses to physiological conditions (i.e. dynamic exercise and orthostatic stress) across areas in the brain and/or head.

Hypercapnic cerebral CO2 reactivity in global CBF was greater than the hypocapnic reactivity (Ide et al. 2003) (Table 3). The mechanisms underlying this greater reactivity to hypercapnia compared with hypocapnia may be related to a greater influence of vasodilator mediators on intracranial vascular tone compared with vasoconstrictive mediators (Toda & Okamura, 1998; Ainslie & Duffin, 2009). In humans, Peebles et al.(2008) recently reported that, during hypercapnia, there is a large release of nitric oxide (NO) from the brain, whereas this response was absent during hypocapnia.

The difference in CO2 reactivity between vertebro-basilar territories (VA and BA) and the cerebral cortex (ICA and MCA) may be due to diverse characteristics of vasculature, e.g. regional microvascular density (Sato et al. 1984), basal vascular tone (Ackerman, 1973; Haubrich et al. 2004; Reinhard et al. 2008), autonomic innervation (Edvinsson et al. 1976; Hamel et al. 1988) and regional heterogeneity in ion channels or production of NO (Iadecola & Zhang, 1994; Gotoh et al. 2001).

Interestingly, the response of the ECA to changes in CO2 may be similar to other peripheral arteries. It has long been appreciated that the vasodilatory effect of hypercapnia is much more profound in cerebral than in peripheral vasculature, particularly leg (Lennox & Gibbs, 1932; Ainslie et al. 2005) and brachial arteries (Miyazaki, 1973). These findings suggest that control of CO2 is particularly important in the cerebral circulation. The high resting metabolic requirements of the brain, compared with that of other vasculature, might be one reason why this circulatory arrangement is desirable (Ainslie et al. 2005). Specifically, high CO2 reactivity may be a way for the brain to match metabolism with flow (Ainslie et al. 2005).

Lower CO2reactivity in the vertebro-basilar system may be important for maintaining central respiratory function because Graphic in central chemoreceptors is regulated by Graphic and blood flow to maintain breathing stability.

In summary, our study shows that cerebral CO2 reactivity in the vertebro-basilar circulation is lower than that in the internal carotid circulation, while CO2 reactivity in the external carotid circulation is much lower compared with two other cerebral arteries. These findings indicate a difference in cerebral CO2 reactivity between different circulatory areas in the brain and head, which may explain different CBF responses to physiological stress. Lower CO2 reactivity in the vertebro-basilar system may be beneficial for preserving blood flow to the medulla oblongata to maintain vital systemic functions, while higher CO2 reactivity in the internal carotid system may imply a larger tolerance for varied blood flow in the cerebral cortex.

Preventing overtraining in athletes in high-intensity sports and stress/recovery monitoring

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Nevner de fleste faktorene rundt restitusjon. Og legger vekt på at idrettsutøvere er under-restituert heller enn over-trent. Beskriver spørreskjemaet RESTQ-Sport som kan brukes til å følge med på restitusjonseffekten hos en idrettsutøver.

http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0838.2010.01192.x/full

The key defining features are

  • •
    Recovery is a process in time and is dependent on the type of and duration of stress.
  • •
    Recovery depends on a reduction of stress, a change of stress, or a break from stress.
  • •
    Recovery is specific to the individual and depends on individual appraisal.
  • •
    Recovery can be passive, active, or pro-active.
  • •
    Recovery is closely tied to situational conditions.

Furthermore, Kellmann und Kallus (2001) defined recovery as

an inter-individual and intra-individual multi-level (e.g., psychological, physiological, social) process in time for the re-establishment of performance abilities. Recovery includes an action-oriented component, and those self-initiated activities (proactive recovery) can be systematically used to optimize situational conditions and to build up and refill personal resources and buffers (p. 22).

This definition also demonstrates the complexity of recovery, as discussed in more detail by Kellmann (2002a), and highlights the need to individually tailor recovery activities.

The RESTQ-Sport consists of 77 items (19 scales with four items each plus one warm-up item), which the participants answer retrospectively. A Likert-type scale is used with values ranging from 0 (never) to 6 (always) indicating how often the respondent participated in various activities during the past 3 days/nights. High scores in the stress-associated activity scales reflect intense subjective stress, whereas high scores in the recovery-oriented scales indicate good recovery activities.

The RESTQ-Sport consists of seven general stress scales (General Stress, Emotional Stress, Social Stress, Conflicts/Pressure, Fatigue, Lack of Energy, Physical Complaints), five general recovery scales (Success, Social Recovery, Physical Recovery, General Well-being, Sleep Quality), three sport-specific stress scales (Disturbed Breaks, Emotional Exhaustion, Injury), and four sport-specific recovery scales (Being in Shape, Personal Accomplishment, Self-Efficacy, Self-Regulation). Examples of items would be: “In the past (3) days/nights … my body felt strong” (for the scale Being in Shape) or “In the past (3) days/nights … I had a satisfying sleep” (for the scale Sleep Quality).

When talking to coaches, it appears easier to frame the current topic as underrecovery rather than overtraining. It is the coaches’ job to train athletes at the optimal level (which is often at the limit); however, they should also avoid overtraining. Coaches may be much more receptive to working with the concept of underrecovery because it acknowledges that underrecovery can also be due to factors, which are outside of their control. The diagnosis of overtraining and underrecovery, should be determined only by an interdisciplinary team that is able and willing to share the data to allow for a comprehensive assessment of the athlete. To optimize this process, the consultation of athletes should be conducted in consultation with coaches, sport physicians, and sport psychologists. Consequently, all physiological and psychological data, as well as training and performance data should be shared on an interdisciplinary basis (Kellmann, 2002a; Smith & Norris, 2002). Assessment should include a complete training documentation, the assessment of subjective and objective physiological and psychological data, and the integration of an athletes’ perspective. It is important that psychological testing like lactate testing, also be part of the regular training routine. Furthermore, research in sport psychology should systematically focus on psychological interventions, which help to optimize the recovery process, ideally in combination with physiological interventions.

The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

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Nevner det meste rundt behandling av muskel og skjelett problemer, både usikkerheter, manglende diagnostisk spesifisitet, dårlig forhold mellom forklaringsmodelle og realitet, og foreslår nevrosentriske forklaringsmodeller. Viser til at spesifikk behandling ikke har bedre effekt enn uspesifikk behandling. Og til at den mekaniske teknikken setter igang en kaskade av nevrologiske effekter som resulterer i en behandlingeffekt.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775050/

Abstract

Prior studies suggest manual therapy (MT) as effective in the treatment of musculoskeletal pain; however, the mechanisms through which MT exerts its effects are not established. In this paper we present a comprehensive model to direct future studies in MT. This model provides visualization of potential individual mechanisms of MT that the current literature suggests as pertinent and provides a framework for the consideration of the potential interaction between these individual mechanisms. Specifically, this model suggests that a mechanical force from MT initiates a cascade of neurophysiological responses from the peripheral and central nervous system which are then responsible for the clinical outcomes. This model provides clear direction so that future studies may provide appropriate methodology to account for multiple potential pertinent mechanisms.

Mechanical Stimulus 

First, only transient biomechanical effects are supported by studies which quantify motion (Colloca et al., 2006;Gal et al., 1997;Coppieters & Butler, 2007;Coppieters & Alshami, 2007) but not a lasting positional change (Tullberg et al., 1998;Hsieh et al., 2002). Second, biomechanical assessment is not reliable. Palpation for position and movement faults has demonstrated poor reliability (Seffinger et al., 2004;Troyanovich et al., 1998) suggesting an inability to accurately determine a specific area requiring MT.  Third, MT techniques lack precision as nerve biased techniques are not specific to a single nerve (Kleinrensink et al., 2000) and joint biased technique forces are dissipated over a large area (Herzog et al., 2001;Ross et al., 2004).

Finally, studies have reported improvements in signs and symptoms away from the site of application such as treating cervical pain with MT directed to the thoracic spine (Cleland et al., 2005;Cleland et al., 2007) and lateral epicondylitis with MT directed to the cervical spine (Vicenzino et al., 1996).

Subsequently, we suggest, that as illustrated by the model, a mechanical force is necessary to initiate a chain of neurophysiological responses which produce the outcomes associated with MT. 

Neurophysiological Mechanism 

Studies have measured associated responses of hypoalgesia and sympathetic activity following MT to suggest a mechanism of action mediated by the periaquaductal gray (Wright, 1995) and lessening of temporal summation following MT to suggest a mechanism mediated by the dorsal horn of the spinal cord (George et al., 2006) The model makes use of directly measurable associated responses to imply specific neurophysiological mechanisms when direct observations are not possible. The model categorizes neurophysiological mechanisms as those likely originating from a peripheral mechanism, spinal cord mechanisms, and/or supraspinal mechanisms.

Peripheral mechanism 

Musculoskeletal injuries induce an inflammatory response in the periphery which initiates the healing process and influences pain processing. Inflammatory mediators and peripheral nociceptors interact in response to injury and MT may directly affect this process. For example, (Teodorczyk-Injeyan et al., 2006) observed a significant reduction of blood and serum level cytokines in individuals receiving joint biased MT which was not observed in those receiving sham MT or in a control group. Additionally, changes of blood levels of β-endorphin, anandamide, N-palmitoylethanolamide, serotonin, (Degenhardt et al., 2007) and endogenous cannabinoids (McPartland et al., 2005) have been observed following MT. Finally, soft tissue biased MT has been shown to alter acute inflammation in response to exercise (Smith et al., 1994) and substance P levels in individuals with fibromyalgia (Field et al., 2002). Collectively, these studies suggest a potential mechanism of action of MT on musculoskeletal pain mediated by the peripheral nervous system for which mechanistic studies may wish to account. 

Spinal mechanisms 

MT may exert an effect on the spinal cord. For example, MT has been suggested to act as a counter irritant to modulate pain (Boal & Gillette, 2004) and joint biased MT is speculated to “bombard the central nervous system with sensory input from the muscle proprioceptors (Pickar & Wheeler, 2001).”Subsequently, a spinal cord mediated mechanism of MT must be considered and is accounted for in the model. Direct evidence for such an effect comes from a study (Malisza et al., 2003b) in which joint biased MT was applied to the lower extremity of rats following capsaicin injection. A spinal cord response was quantified by functional MRI during light touch to the hind paw. A trend was noted towards decreased activation of the dorsal horn of the spinal cord following the MT. The model uses associated neuromuscular responses following MT to provide indirect evidence for a spinal cord mediated mechanism. For example, MT is associated with hypoalgesia (George et al., 2006;Mohammadian et al., 2004;Vicenzino et al., 2001), afferent discharge (Colloca et al., 2000;Colloca et al., 2003), motoneuron pool activity (Bulbulian et al., 2002;Dishman & Burke, 2003), and changes in muscle activity (Herzog et al., 1999;Symons et al., 2000) all of which may indirectly implicate a spinal cord mediated effect.

Supraspinal mechanisms 

Finally, the pain literature suggests the influence of specific supraspinal structures in response to pain. Structures such as the anterior cingular cortex (ACC), amygdala, periaqueductal gray (PAG), and rostral ventromedial medulla (RVM) are considered instrumental in the pain experience.(Peyron et al., 2000;Vogt et al., 1996;Derbyshire et al., 1997;Iadarola et al., 1998;Hsieh et al., 1995;Oshiro et al., 2007;Moulton et al., 2005;Staud et al., 2007;Bee & Dickenson, 2007;Guo et al., 2006). Subsequently, the model considers potential supraspinal mechanisms of MT. Direct support for a supraspinal mechanism of action of MT comes from (Malisza et al., 2003a) who applied joint biased MT to the lower extremity of rats following capsaicin injection. Functional MRI of the supraspinal region quantified the response of the hind paw to light touch following the injection. A trend was noted towards decreased activation of the supraspinal regions responsible for central pain processing. The model accounts for direct measures of supraspinal activity along with associated responses such as autonomic responses (Moulson & Watson, 2006;Sterling et al., 2001;Vicenzino et al., 1998) (Delaney et al., 2002;Zhang et al., 2006), and opiod responses (Vernon et al., 1986) (Kaada & Torsteinbo, 1989) to indirectly imply a supraspinal mechanism. Additionally, variables such as placebo, expectation, and psychosocial factors may be pertinent in the mechanisms of MT (Ernst, 2000;Kaptchuk, 2002). For example expectation for the effectiveness of MT is associated with functional outcomes (Kalauokalani et al., 2001) and a recent systematic review of the literature has noted that joint biased MT is associated with improved psychological outcomes (Williams et al., 2007). For this paper we categorize such factors as neurophysiological effects related to supraspinal descending inhibition due to associated changes in the opioid system (Sauro & Greenberg, 2005), dopamine production (Fuente-Fernandez et al., 2006), and central nervous system (Petrovic et al., 2002;Wager et al., 2004;Matre et al., 2006) which have been observed in studies unrelated to MT.

Figure 3 Pathway considering both a spinal cord and supraspinal mediated effect from Bialosky et al (2008)

Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension

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Denne beskriver hvordan regulering av pusten kan påvirke vagus nerven til å dempe betennelser og redusere CRP (en betennelsesmarkør) i blodet.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2012.02523.x/full

Objectives.  A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6).

Design.  Subjects diagnosed with hypertension (n = 45, age 35–64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15–0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure.

Results.  Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (β =−0.25±0.1, P = 0.02), baroreflex sensitivity (β = −0.33±0.7, P = 0.04) and RR interval (β = −0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6.

Conclusions.  Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Chronic low-grade inflammation contributes to the development of experimental and clinical hypertension [1–3], and it increases the risk for myocardial infarction, stroke and sudden cardiac death [4]. C-reactive protein (CRP) is an established index of systemic inflammation. It is produced chiefly by hepatocytes under the regulation of a cascade of pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α), interleukin-1ß [IL-1ß] and IL-6] that are expressed in response to conditions that include vascular injury and infection. In addition, CRP is produced by human coronary artery smooth muscle cells following exposure to pro-inflammatory cytokines [5], which suggests that it may contribute independently to endothelial dysfunction and atherogenesis [6].

Clinical trials that have attempted to modify vagal efferent activity by means of aerobic exercise [17, 18], resistance exercise [19] or device-guided vagal nerve stimulation [20–22] have yet to demonstrate consequent reduction in pro-inflammatory activity that is independent of confounding factors such as anti-inflammatory medications.

Subjects received four weekly and two biweekly 1-h sessions of behavioural neurocardiac training or autogenic relaxation, as described previously [23]. Home practice sessions complemented the laboratory-based training. All sessions began with a 10-min review of cognitive-behavioural guidelines for managing daily stress [25].

At the completion of each task, subjects were trained to cognitively disengage from negative or aroused affect and to focus attention on slowing respiration (within their comfort zone) to 10-s cycles (6 breaths min−1). During each countering exercise, subjects were guided by the use of biofeedback to increase RR spectral power at approximately 0.1 Hz, as shown on a biofeedback display of the RR power spectrum (0.003–0.5 Hz) and breaths min−1.

The major finding of this study is that following an 8-week protocol of behavioural neurocardiac training or autogenic relaxation amongst patients with hypertension, change in hsCRP was associated independently and inversely with changes in tonic and reflex vagal heart rate modulation as measured by RR high-frequency power (ms2 per Hz), baroreflex sensitivity (ms per mmHg) and lengthening of the RR interval (ms). A statistical trend in the data suggested a similar inverse association between changes in IL-6 and RR high-frequency power.

A central hypothesis of the cholinergic anti-inflammatory reflex model is that the innate immune response is regulated, in part, by rapid and localized efferent activity of the vagus nerve. Previous reviews have identified the functional anatomy and neural mechanisms of this model [10, 29, 30]. In brief, efferent fibres of the vagus nerve comprise a neural anti-inflammatory pathway that culminates in the release of acetylcholine in proximate sites where pro-inflammatory factors have been expressed. Acetylcholine has been shown to bind to subunit α7 of nicotinic acetylcholine receptors on cytokine-producing immune cells [30]. This inhibits the activation of NF-κB and the subsequent expression of a pro-inflammatory cascade that includes TNF-α, IL-6 and CRP [10].

To our knowledge, the present proof of principle study involving hypertensive patients provides the most direct evaluation of whether augmentation of tonic or reflex vagal heart rate modulation, in this instance by a behavioural intervention, attenuates independently pro-inflammatory activity as assessed by hsCRP and IL-6. It is noteworthy that the present findings were observed following only modest changes in markers of vagal HR modulation. Previous behavioural trials of heart rate variability biofeedback or relaxation [32–34] have reported a small but statistically significant increase in vagal HR modulation. Similarly, behavioural training is associated with a modest, but statistically significant decrease in proinflammatory factors, including hsCRP and IL-6 [35], although heart rate variability biofeedback failed to reduce other inflammatory factors following experimental administration of an endotoxin (lipopolysaccharide) [36].

In sum, the present findings support the model of a cholinergic anti-inflammatory reflex when pro-inflammatory activity is measured by hsCRP. Clinical trial evidence has demonstrated that behavioural interventions can significantly augment vagal heart rate modulation or cardiovagal baroreflex gain through the use of relaxation training and biofeedback [32–34].

Vagal tone and the inflammatory reflex

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En studie som beskriver mekanismene bak hvordan vagus nerven henger sammen med immunsystemet. Med en sterk vagusnerve (høy HRV) kan betennelser dempes.

http://www.ccjm.org/content/76/Suppl_2/S23.long

Inhibition of sympathoexcitatory circuits is influenced by cerebral structures and mediated via vagal mechanisms. Studies of pharmacologic blockade of the prefrontal cortex together with neuroimaging studies support the role of the right hemisphere in parasympathetic control of the heart via its connection with the right vagus nerve. Neural mechanisms also regulate inflammation; vagus nerve activity inhibits macrophage activation and the synthesis of tumor necrosis factor in the reticuloendothelial system through the release of acetylcholine. Data suggest an association between heart rate variability and inflammation that may support the concept of a cholinergic anti-inflammatory pathway.

The neurovisceral integration model of cardiac vagal tone integrates autonomic, attentional, and affective systems into a functional and structural network. This neural network can be indexed by heart rate variability (HRV). High HRV is associated with greater prefrontal inhibitory tone. A lack of inhibition leads to undifferentiated threat responses to environmental challenges.

The cholinergic anti-inflammatory pathway

Acetylcholine and parasympathetic tone inhibit proinflammatory cytokines such as interleukin (IL)-6. These proinflammatory cytokines are under tonic inhibitory control via the vagus nerve, and this function may have important implications for health and disease.5

The cholinergic anti-inflammatory pathway is associated with efferent activity in the vagus nerve, leading to acetylcholine release in the reticuloendothelial system that includes the liver, heart, spleen, and gastrointestinal tract. Acetylcholine interacts with the alpha-7 nicotinic receptor on tissue macrophages to inhibit the release of proinflammatory cytokines, but not anti-inflammatory cytokines such as IL-10.

Approximately 80% of the fibers of the vagus nerve are sensory; ie, they sense the presence of proinflammatory cytokines and convey the signal to the brain. Efferent vagus nerve activity leads to the release of acetylcholine, which inhibits tumor necrosis factor (TNF)-alpha on the macrophages. Cytokine regulation also involves the sympathetic nervous system and the endocrine system (the hypothalamic-pituitary axis).

Inverse relationship between HRV and CRP

In a study of 613 airplane factory workers in southern Germany, vagally mediated HRV was inversely related to high-sensitivity CRP in men and premenopausal women, even after controlling for urinary norepinephrine as an index of sympathetic activity.6

Inverse relationship between HRV and fibrinogen

In a related report from the same study, vagal modulation of fibrinogen was investigated.7 Fibrinogen is a large glycoprotein that is synthesized by the liver. Plasma fibrinogen is a measure of systemic inflammation crucially involved in atherosclerosis.

CONCLUSION

The brain and the heart are intimately connected. Both epidemiologic and experimental data suggest an association between HRV and inflammation, including similar neural mechanisms. Evidence of an association between HRV and inflammation supports the concept of a cholinergic anti-inflammatory pathway.

Effect of short-term practice of breathing exercises on autonomic functions in normal human volunteers

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Nevner hvordan sakte pust bedrer tilstanden i det autonome nervesystem. De bruker 6 sek inn og 6 sek ut i denne studien, som stimulerer vagusnerven best.

Klikk for å få tilgang til 0807.pdf

Background & objectives: Practice of breathing exercises like pranayama is known to improve autonomic function by changing sympathetic or parasympathetic activity. Therefore, in the present study the effect of breathing exercises on autonomic functions was performed in young volunteers in the age group of 17-19 yr.

Methods: A total of 60 male undergraduate medical students were randomly divided into two groups: slow breathing group (that practiced slow breathing exercise) and the fast breathing group (that practiced fast breathing exercise). The breathing exercises were practiced for a period of three months. Autonomic function tests were performed before and after the practice of breathing exercises.

Results: The increased parasympathetic activity and decreased sympathetic activity were observed in slow breathing group, whereas no significant change in autonomic functions was observed in the fast breathing group.

Interpretation & conclusion: The findings of the present study show that regular practice of slow breathing exercise for three months improves autonomic functions, while practice of fast breathing exercise for the same duration does not affect the autonomic functions.

One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?

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Alt om hvordan melatonin virker som en antioksidant. Jo større ROS utfordring vi har, jo mer spiser det av melatoninlagrene våre. Når vi får mindre ROS, feks gjennom kostholdsendringer og stressreduksjon, så økes melatonin igjen.

http://www.ncbi.nlm.nih.gov/pubmed/17198536

Melatonin is a highly conserved molecule. Its presence can be traced back to ancient photosynthetic prokaryotes. A primitive and primary function of melatonin is that it acts as a receptor-independent free radical scavenger and a broad-spectrum antioxidant. The receptor-dependent functions of melatonin were subsequently acquired during evolution. In the current review, we focus on melatonin metabolism which includes the synthetic rate-limiting enzymes, synthetic sites, potential regulatory mechanisms, bioavailability in humans, mechanisms of breakdown and functions of its metabolites. Recent evidence indicates that the original melatonin metabolite may be N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) rather than its commonly measured urinary excretory product 6-hydroxymelatonin sulfate. Numerous pathways for AFMK formation have been identified both in vitro and in vivo. These include enzymatic and pseudo-enzymatic pathways, interactions with reactive oxygen species (ROS)/reactive nitrogen species (RNS) and with ultraviolet irradiation. AFMK is present in mammals including humans, and is the only detectable melatonin metabolite in unicellular organisms and metazoans. 6-hydroxymelatonin sulfate has not been observed in these low evolutionary-ranked organisms. This implies that AFMK evolved earlier in evolution than 6-hydroxymelatonin sulfate as a melatonin metabolite. Via the AFMK pathway, a single melatonin molecule is reported to scavenge up to 10 ROS/RNS. That the free radical scavenging capacity of melatonin extends to its secondary, tertiary and quaternary metabolites is now documented. It appears that melatonin’s interaction with ROS/RNS is a prolonged process that involves many of its derivatives. The process by which melatonin and its metabolites successively scavenge ROS/RNS is referred as the free radical scavenging cascade. This cascade reaction is a novel property of melatonin and explains how it differs from other conventional antioxidants. This cascade reaction makes melatonin highly effective, even at low concentrations, in protecting organisms from oxidative stress. In accordance with its protective function, substantial amounts of melatonin are found in tissues and organs which are frequently exposed to the hostile environmental insults such as the gut and skin or organs which have high oxygen consumption such as the brain. In addition, melatonin production may be upregulated by low intensity stressors such as dietary restriction in rats and exercise in humans.

Intensive oxidative stress results in a rapid drop of circulating melatonin levels. This melatonin decline is not related to its reduced synthesis but to its rapid consumption, i.e. circulating melatonin is rapidly metabolized by interaction with ROS/RNS induced by stress. Rapid melatonin consumption during elevated stress may serve as a protective mechanism of organisms in which melatonin is used as a first-line defensive molecule against oxidative damage. The oxidative status of organisms modifies melatonin metabolism. It has been reported that the higher the oxidative state, the more AFMK is produced. The ratio of AFMK and another melatonin metabolite, cyclic 3-hydroxymelatonin, may serve as an indicator of the level of oxidative stress in organisms.