Trigger point dry needling as an adjunct treatment for a patient with adhesive capsulitis of the shoulder.

Nevner at dry needling gir en raskere smertereduksjon og bevegelsesøkning ved frozen shoulder. 10 behandlinger ble gjort i dette tilfelle.



Prognosis for adhesive capsulitis has been described as self-limiting and can persist for 1 to 3 years. Conservative treatment that includes physical therapy is commonly advised.


The patient was a 54-year-old woman with primary symptoms of shoulder pain and loss of motion consistent with adhesive capsulitis. Manual physical therapy intervention initially consisted of joint mobilizations of the shoulder region and thrust manipulation of the cervicothoracic region. Although manual techniques seemed to result in some early functional improvement, continued progression was limited by pain. Subsequent examination identified trigger points in the upper trapezius, levator scapula, deltoid, and infraspinatus muscles, which were treated with dry needling to decrease pain and allow for higher grades of manual intervention.


The patient was treated for a total of 13 visits over a 6-week period. After trigger point dry needling was introduced on the third visit, improvements in pain-free shoulder range of motion and functional outcome measures, assessed with the Shoulder Pain and Disability Index and the shortened form of the Disabilities of the Arm, Shoulder and Hand questionnaire, exceeded the minimal clinically important difference after 2 treatment sessions. At discharge, the patient had achieved significant improvements inshoulder range of motion in all planes, and outcome measures were significantly improved.


This case report describes the clinical reasoning behind the use of trigger point dry needlingin the treatment of a patient with adhesive capsulitis. The rapid improvement seen in this patient following the initiation of dry needling to the upper trapezius, levator scapula, deltoid, and infraspinatus muscles suggests that surrounding muscles may be a significant source of pain in this condition.

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

Denne beskriver endocannabinoider(eCB) og hvordan man kan øke produksjonen av dem og reseptorene for dem. eCB er et kroppens viktigste naturlige smertstillende stoffer som kan produseres og påvirker alle nerver i kroppen. Spesielt viktig i hjernen, men også i det perifere nervesystem.

Massasje, kiropraktikk og hard trening (f.eks. runners high) utløser eCB i kroppen. Det gjør også omegabalanse (mer n-3), probiotica, NSAIDs, m.m. Også yoga, meditasjon, pust og andre stressreduserende påvirker eCB. Og trening, men kun om man gjør det jevnlig over tid.

Den nevner at langvarig stress reduserer eCB i kroppen siden det er koblet til kortisol. Men den nevner også at noen tilstander kan ha forhøyet eCB i kroppen, f.eks. overvekt.

Med høyt nivå av n-6 relativt til n-3 blir det en overvekt av AA (arakidonsyre) som produserer en overvekt av eCB, som dermed fører til en reduksjon av eCB reseptorer. Dette gjør at smertestillende medikamenter fungerer dårligere, og at det blir lettere kronisk smerte. Tilskudd av n-3 gjør at eCB reseptorene øker. Studiene er gjort på mus og innebærer 17 g/kg.

The endocannabinoid (eCB) system consists of receptors, endogenous ligands, and ligand metabolic enzymes. Metaphorically the eCB system represents a microcosm of psychoneuroimmunology or mind-body medicine. Cannabinoid receptor 1 (CB1) is the most abundant G protein-coupled receptor expressed in the brain, with particularly dense expression in (rank order): the substantia nigra, globus pallidus, hippocampus, cerebral cortex, putamen, caudate, cerebellum, and amygdala [1]. CB1 is also expressed in non-neuronal cells, such as adipocytes and hepatocytes, and in musculoskeletal tissues. Cannabinoid receptor 2 (CB2) is principally associated with cells governing immune function, although it may also be expressed in the central nervous [2][3].

The eCB system’s salient homeostatic roles have been summarized as, “relax, eat, sleep, forget, and protect” [5]. It modulates embryological development, neural plasticity, neuroprotection, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and most importantly from the viewpoint of recent drug development: hunger, feeding, and metabolism. Obese individuals seem to display an increased eCB tone, driving CB1activation in a chronic, feed-forward dysfunction (reviewed by [6]).

Other diseases are associated with suboptimal functioning of the eCB system. Russo [8]proposed that migraine, fibromyalgia, irritable bowel syndrome, and related conditions represent CEDS, “clinical endocannabinoid deficiency syndromes.” Fride [9] speculated that a dysfunctional eCB system in infants contributes to “failure to thrive” syndrome. Hill and Gorzalka [10] hypothesized that deficient eCB signaling could be involved in the pathogenesis of depressive illnesses. In human studies, eCB system deficiencies have been implicated in uncompensated schizophrenia [11], migraine [12], multiple sclerosis [13], Huntington’s [14],[15], uncompensated Parkinson’s [16], irritable bowel syndrome [17], uncompensated anorexia[18], and chronic motion sickness [19].

NSAIDs inhibit two cyclooxygenase (COX) enzymes, COX1 and COX2, and thereby block the conversion of arachidonic acid (AA) into inflammatory prostaglandins. Ibuprofen, ketorolac, and flurbiprofen also block the hydrolysis of AEA into arachidonic acid and ethanolamine [27]. SeeFigure 2. A binding site for some NSAIDs on FAAH has also been identified [28]. NSAID inhibition of COX2 blocks the metabolism of AEA and 2-AG into prostaglandin ethanolamides (PG-EAs) and prostaglandin glycerol esters (PG-GEs), respectively [29].

Combining NSAIDs with cannabinoids (either eCBs or exogenous cannabinoids) produces additive or synergistic effects. A sub-effective dose of WIN55,212-2 became fully antinociceptive following administration of indomethacin in rats [36].

In summary, preclinical studies indicate that some NSAIDs inhibit FAAH and enhance the activity of eCBs, phytocannabinoids, and synthetic cannabinoids. Combinational effects may be particularly relevant at peripheral sites, such as the peripheral terminals of nociceptors.

The distribution of glucocorticoid receptors (GRs) and CB1 overlap substantially in the central nervous system and other tissues, as do GRs and CB2 in immune cells. Dual activation of GRs and CBs may participate in glucocorticoid-mediated anti-inflammatory activity, immune suppression, insulin resistance, and acute psychoactive effects.

The acute administration of glucocorticoids may shift AA metabolism toward eCB synthesis in parts of the brain.

Chronic exposure to glucocorticoids downregulates the eCB system. Chronic corticosterone administration decreased CB1 densities in rat hippocampus [59] and mouse hippocampus and amygdala [61]. Chronic corticosterone administration in male rats led to visceral hyperalgesia in response to colorectal distension, accompanied by increased AEA, decreased CB1 expression, and increased TRPV1 expression in dorsal root ganglia. Co-treatment with the corticoid receptor antagonist RU-486 prevented these changes [62].

Polyunsaturated fatty acids (PUFAs) play fundamental roles in many cellular and multicellular processes, including inflammation, immunity, and neurotransmission. They must be obtained through diet, and a proper balance between omega-6 (ω-6) PUFAs and ω-3 PUFAs is essential. The typical Western diet contains a surfeit of ω-6s and a deficiency of ω-3s [130].

The inflammatory metabolites of AA are countered by dietary ω-3s. The two best-known ω-3s are eicosapentaenoic acid (EPA, 20:5ω-3) and docosahexaenoic acid (DHA, 22:6ω-3).

eCBs are derived from AA (see Figure 2). Several preclinical studies showed that dietary supplementation with AA increased serum levels of AEA and 2-AG, summarized in Table 1. Although we clearly need AA to biosynthesize eCBs, excessive levels of AA, administered chronically, may lead to excessive levels of eCBs. This in turn may lead to desensitized and downregulated CB1 and CB2 receptors.

Dietary supplementation with ω-3s predictably increased the concentration of EPA and/or DHA in tissues, cells, and plasma, and decreased the relative concentration of AA in tissues, cells, and plasma [132][133]. ω-3 supplementation also decreased AEA and 2-AG in tissues, cells, and plasma (Table 1).

Adequate levels of dietary ω-3s are required for proper eCB signaling. Mice supplemented with ω-3s, compared to mice on a control diet, expressed greater levels of CB1 and CB2 mRNA.

n summary, dietary ω-3s seem to act as homeostatic regulators of the eCB system. In obese rodents fed a high-AA diet, ω-3s significantly decrease eCBs, especially 2-AG, particularly in tissues that become dysregulated, such as adipose and liver tissues. Plasma eCB levels are reduced by krill oil also in obese humans. Little change in eCB levels are seen in normo-weight individuals not fed a high ω-6 diet, and dietary ω-3s are required for proper eCB signaling.

Human intestinal epithelial cells incubated with L. acidophilus produced more CB2 mRNA [145]. Feeding L. acidophilus to mice and rats increased the expression of CB2 mRNA in colonic epithelial cells. Lastly, mice fed L. acidophilus showed less pain behavior following colonic distension with butyrate than control mice, an effect reversed by the CB2 antagonist AM630[145].

Chronic or repeated stress results in a chronic elevation of endogenous corticosterone via the hypothalamic-pituitary-adrenocortical (HPA) axis. Chronic stress (repeated restraint) reduced AEA levels throughout the corticolimbic stress circuit in rodents [99][196][197].

In summary, chronic stress impairs the eCB system, via decreased levels of AEA and 2-AG. Changes in CB1 expression are more labile. Stress management may reverse the effects of chronic stress on eCB signaling, although few studies exploring this possibility have been performed to date. Clinical anecdotes suggests that stress-reduction techniques, such as meditation, yoga, and deep breathing exercises impart mild cannabimimetic effects [218].

Massage and osteopathic manipulation of asymptomatic participants increased serum AEA 168% over pretreatment levels; mean OEA levels decreased 27%, and no changes occurred in 2-AG. Participants receiving sham manipulation showed no changes [218].

Upregulation of the eCB system in obese humans seems to be driven by excessive production of eCBs in several peripheral tissues such as visceral adipose tissue, liver, pancreas, and skeletal muscle.

In summary, increased food intake, adiposity, and elevated levels of AEA and 2-AG apparently spiral in a feed-forward mechanism. Weight loss from caloric restriction breaks the cycle, possibly by reducing CB1 expression and reducing eCB levels.

Although both types of exercise regimens increased eCB ligand concentrations, only long-term-forced exercise led to sustained elevations of eCBs, and predictable CB1 downregulation.

In whole animals, however, caffeine’s effects are biphasic and vary by dosage and acute versus chronic administration. In humans, the acute administration of caffeine decreases headache pain, but exposure to chronic high doses, ≥300 mg/day, may exacerbate chronic pain [275].

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

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.


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)

Neurobiologic basis of craving for carbohydrates.

Denne studen nevner 5 systemer som bidrar til at vi føler behov for karbohydrater. Den viktigste er at serotonin øker i hjernen, noe som over tid kan gi en avhengighet. De nevner også at evnen til å skille sult fra andre interne følelser kan bli dårligere, og at det gir behov for mat når andre ting i kropp og sinn er i ulage.

Serotonergic:  Increased brain serotonin improves mood. Brain serotonin levels depend on the availability of its Trp precursor. Dietary carbohydrates increase the passage of Trp through the blood–brain barrier, unlike proteins, which alter LNAA.  Faced with anxiety, an individual eats carbohydrates, which increase brain serotonin, thus improving mood.

Palatability and hedonic response: The pleasurable experience of eating food with high palatability immediately improves mood. This occurs in individuals with greater genetic sensitivity to sweet taste through the activation of the endogenous opioid system. Faced with anxiety, an individual eats a food with high palatability, activating the hedonic mechanism, which improvesmood.

Motivational system:  Carbohydrates act in the motivational system in the same manner as abused substances. This increases dopamine and endogenous opioids, which are associated with a known pleasurable effect, improving mood. If this behavior is repeated over time, structural changes in the brain are produced that generate dependence on highly palatable foods.

Stress response: Faced with anxiety associated with stress, the HPA axis activates. Highly palatable foods activate the motivational system and reduce the HPA axis, thus regulating the stress system. Therefore, when faced with anxiety, highly palatable food produces a hedonic reward as well as reducing the state of anxiety.

Gene–environment:  Eating is a coping tool to relieve negative emotions. The behavior is learned through inadequate parenting and environment. It also stems from an inability to distinguish hunger from other aversive internal states. There is greater susceptibility in carriers of the A1 allele of the DRD2 dopamine receptor and carriers of the short allele of the serotonin transporter gene.

A new view on hypocortisolism

Om lavt kortisol-nivå og at det har en beskyttende effekt på kroppen etter langvarig høyt kortisol-nivå. En ny måte å se det på. Det er faktisk en overlevelsesmekanisme. Hvis vi ikke greier å skru av stresset eller fjerne oss fra den stressende livssituasjonen, vil kroppen etter hvert skru av stressresponsen og vi blir oversensitive for enhver utfordring. Utmattelse, muskelsmerter og fibromyalgi blir resultatet. Men likevel er det bedre for organismen enn videre stressresons. Studien forteller hvordan kortisol påvirker sentralnervesystemet, immunsystemet, oppvåkningsresponsen om morgenen, sickness responce, allostatic load, m.m.

Low cortisol levels have been observed in patients with different stress-related disorders such as chronic fatigue syndrome, fibromyalgia, and post- traumatic stress disorder. Data suggest that these disorders are characterized by a symptom triad of enhanced stress sensitivity, pain, and fatigue.

We propose that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the hypothalamic–pituitary– adrenal axis due to chronic stress as illustrated in an animal model. Further evidence suggests that despite symptoms such as pain, fatigue and high stress sensitivity, hypocortisolism may also have beneficial effects on the organism. This assumption will be underlined by some studies suggesting protective effects of hypocortisolism for the individual.

Since the work of Selye (1936), stress has been associated with an activation of the hypothalamic– pituitary–adrenal (HPA) axis resulting in an increased release of cortisol from the adrenal glands. In recent years, a phenomenon has been described that is characterized by a hyporespon- siveness on different levels of the HPA axis in a number of stress-related states. This phenomenon, termed ‘hypocortisolism’, has been reported in about 20–25% of patients with stress-related dis- orders such as chronic fatigue syndrome (CFS), chronic pelvic pain (CPP), fibromyalgia (FMS), post-traumatic stress disorder (PTSD), irritable bowel syndrome (IBS), low back pain (LBP), burn- out, and atypical depression (Griep et al., 1998; Heim et al., 1998, 2000; Pruessner et al., 1999; Gold and Chrousos, 2002; Gur et al., 2004; Roberts et al., 2004; Rohleder et al., 2004). When hypo- cortisolemic, all these disorders may share affiliated syndromes characterized by a triad of enhanced stress sensitivity, pain, and fatigue.

However, despite different definitions we know today that there is a considerable overlap between the disorders.

In the early 1990s, Hudson and colleagues were amongst the first addressing this issue. They published a study on the comorbidity of FMS with medical and psychiatric disorders in which they reported a higher prevalence of migraine, IBS, and CFS, as well as higher lifetime rates of depression and panic disorder in patients with FMS (Hudson et al., 1992).

Thus, numerous studies on male war veterans have reported an association between PTSD and symp- toms such as fatigue, joint pain, and muscle pain (Engel et al., 2000; Ford et al., 2001).

These alterations of HPA axis are determined by (1) a reduced biosynthesis or release of the respective releasing factor/hormone on different levels of the HPA axis (CRF/AVP from the hypothalamus, ACTH from the pituitary, or cortisol from the adrenal glands) accompanied by a subsequent decreased stimulation of the respective target receptors, (2) a hypersecretion of one secretagogue with a subsequent down-regulation of the respective target receptors, (3) an enhanced sensitivity to the negative feedback of glucocorti- coids, (4) a decreased availability of free cortisol, and/ or (5) reduced effects of cortisol on the target tissue, describing a relative cortisol resistance (Heim et al., 2000; Raison and Miller, 2003).

Several years ago we postulated that hypocortiso- lism/a hyporeactive HPA axis might develop after prolonged periods of stress together with a hyper- activity of the HPA axis and excessive glucocorti- coid release (Hellhammer and Wade, 1993). This proposed time course with changes in HPA axis activity from hyper- to hypocortisolism resembles the history of patients with stress-related disorders who frequently report about the onset of ‘hypo- cortisolemic symptoms’ (fatigue, pain, stress sen- sitivity) after prolonged periods of stress, e.g. work stress, infection, or social stress (Buskila et al., 1998; Van Houdenhove and Egle, 2004)

Thinking about the potential cause/reason for changes in HPA axis activity from hyper- to hypocortisolism one might consider the body’s self-adjusting abilities as an important factor. Self-adjusting abilities play a significant role in survival of the organism by counteracting the enduring increased levels of glucocorticoids, and protecting the organism against the possible dele- terious effects thereof.

Poten- tial mechanisms of the ‘HPA axis adjustment’ are (1) the down-regulation of specific receptors on different levels of the axis (hypothalamus, pitu- itary, adrenals, target cells), (2) reduced biosyn- thesis or depletion at several levels of the HPA axis (CRF, ACTH, cortisol) and/or (3) increased negative feedback sensitivity to glucocorticoids (Hellhammer and Wade, 1993; Heim et al., 2000).

The suppressed stress response after administration of dexamethasone demonstrates an increased sensi- tivity to glucocorticoid negative feedback on the level of the pituitary.

The duration, intensity, number and chronicity of stressors may further pronounce these effects. The low-dose dexamethasone test may be the most sensitive measure of this condition.

The HPA axis plays an important role in the regulation of the SNS. CRF seems to increase the spontaneous discharge rate of locus coeruleus (LC) neurons and enhances norepinephrine (NE) release in the prefrontal cortex (Valentino, 1988; Valentino et al., 1993; Smagin et al., 1995), whereas glucocorticoids seem to exert more inhibitory effects on NE release.

Glucocorticoids are the most potent anti-inflam- matory hormones in the body. They act on the immune system by both suppressing and stimulating pro- and anti-inflammatory mediators. While they promote Th2 development, for example by enhan- cing interleukin (IL)-4 and (IL)-10 secretion by macrophages and Th2 cells (Ramierz et al., 1996), they inhibit inflammatory responses and suppress the production and release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF- alpha), IL-1 and IL-6 (see Franchimont et al., 2003).

An important role of glucocorticoids during stress is to suppress the production and activity of pro- inflammatory cytokines, thus restraining the inflammatory reaction and preventing tissue destruction (see McEwen et al., 1997; Ruzek et al., 1999; Franchimont et al., 2003).

Therefore, a hypocortisolemic stress response, as observed in patients with stress-related disorders, may result in an overactivity of the immune system in terms of increased inflammatory responses due to impaired suppressive effects of low cortisol levels (see Heim et al., 2000; Rohleder et al., 2004). This assumption is supported by studies reporting elevated levels of pro-inflammatory cytokines in patients with stress-related disorders such as PTSD, CFS, and FMS (Maes et al., 1999; Patarca-Montero et al., 2001; Thompson and Barkhuizen, 2003; Rohleder et al., 2004).

Assessing the cortisol awakening response in pregnant women, preliminary results from our laboratory suggest that women with higher daily stress load showed lower cortisol levels in the morning compared to women with normal to low daily stress load. This result suggests a possible prevention of harmful stimulatory effects of maternal cortisol on placental CRF, which plays a major role in the initiation of delivery (Rieger, 2005).

The term ‘sickness response’ refers to non-specific symptoms such as fatigue, increased pain sensi- tivity, depressed activity, concentration difficul- ties, and anorexia that accompany the response to infection (Hart, 1988; Maier and Watkins, 1998). Sickness behavior at the behavioral level appears to be the expression of a central motivational state that reorganizes the organism’s priority to cope with infectious pathogens (Hart, 1988).

Further evidence for the protective effects of the development of a hypocortisolism refers to the allostatic load index. The term ‘allostatic load’ was irstly introduced by McEwen and Stellar (1993) describing the wear and tear of the body and brain resulting from chronic overactivity or inactivity of physiological systems that are normally involved in adaptation to environmental challenge. Allostatic load results when the allostatic systems (e.g. the HPA axis) are either overworked or fail to shut off after the stressful event is over or when these systems fail to respond adequately to the initial challenge, leading other systems to overreact (McEwen, 1998). In this context, results of Hell- hammer et al. (2004) demonstrate a significantly higher allostatic load index in older compared to younger subjects with the exception of hypocorti- solemic elderly who had a comparable allostatic load to young people even though they scored far higher on perceived stress scales. Considering the fact that allostatic load has been associated with a higher risk for mortality, these data suggest that a hypocortisolemic response to stress may rather be protective than damaging.

Low cortisol levels in the case of pregnant women may protect the mother and the child against the risk of pre-term birth, which could be harmful for both of them. Similarly, low cortisol levels in those individuals who are repeatedly or continuously exposed to intense immune stimuli may be beneficial for health and survival.

Similarly, low cortisol levels in those individuals who are repeatedly or continuously exposed to intense immune stimuli may be beneficial for health and survival. Most strikingly, the demonstration of a low allostatic load index in hypocortisolemic subjects suggests that a down-regulation of the HPA axis in chroni- cally stressed subjects protects those subjects against the harmful effects of a high allostatic load index.

Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress

Om hvordan diafragmisk pust (med magen) øker antioksidantbeskyttelsen og restitusjonen ved å senke kortison og øke melatonin. Gjort på et 24t sykkerlritt hvor de som gjorde 1t pusteing før de sovnet fikk raskere restitusjon. Nevner direkte sammenheng mellom kortisol og melatonin. Og påstår at pusten bør implementeres i ethvert treningsregime som restitusjon.

Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant

Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

Stress is defined as a physiological reaction to undesired emotional or physical situations. Initially, stress induces an acute response (fight or flight) that is mediated by catecholamines. When stress becomes chronic and lasts for a long time, the stressed organism reacts with physiological alterations to adapt to the unfavorable conditions. This ACTH-mediated reaction affects the immune and neuroendocrine systems, and it is responsible for several diseases [1]. Numerous data support the hypothesis that the pathophysiology of chronic stress can be due, at least partially, to an increase in oxidative stress [24], which may also contributes to heart disease [5,6], rheumatoid arthritis [7,8], hypertension [9,10], Alzheimer’s disease [11,12], Parkinson’s disease [13], atherosclerosis [14] and, finally, aging [15].

High levels of glucocorticoids are known to decrease blood reduced glutathione (GSH) and erythrocyte superoxide dismutase (SOD) activity in rats [20]. Other enzymes are also involved, and NADPH oxidase, xanthine oxidase and uncoupled endothelial nitric oxide synthase are important sources of reactive oxygen species (ROS) in glucocorticoid-induced oxidative stress (see [9] for a review on this argument).

Hormonal reactions to stressors, in particular plasma cortisol levels, are lower in people who meditate than in people who do not [3136], suggesting that it is possible to modulate the neuroendocrine system through neurological pathways. Analysis of oxidative stress levels in people who meditate indicated that transcendental meditation, Zen meditation and Yoga correlate with lower oxidative stress levels [3743].

Melatonin could also be involved in the reduction of oxidative stress because increased levels of this hormone have been reported after meditation [4446]. This neurohormone is considered a strong antioxidant and is used as a treatment for aging. Melatonin in fact, increases several intracellular enzymatic antioxidant enzymes, such as SOD and glutathione peroxidase (GSH-Px) [47,48], and induces the activity of γ-glutamylcysteine synthetase, thereby stimulating the production of the intracellular antioxidant GSH (49]. A number of studies have shown that melatonin is significantly better than the classic antioxidants in resisting free-radical-based molecular destruction. In these in vivostudies, melatonin was more effective than vitamin E, β-carotene [5052] and vitamin C [5355].

Although it has been established that a continuous and moderate physical activity reduces stress, intense and prolonged exercise is deleterious and needs a proper recovery procedure.

Plasma cortisol levels increase in response to intense and prolonged exercise [60,61]. Ponjee et al. [62] demonstrated that cortisol increased significantly in male athletes after they ran a marathon. In another study, plasma ACTH and cortisol were found elevated in highly trained runners and in sedentary subjects after intense treadmill exercise [63].

Most, if not all, meditation procedures involve diaphragmatic breathing (DB), which is the act of breathing deeply into the lungs by flexing the diaphragm rather than the rib cage. DB is relaxing and therapeutic, reduces stress and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices.

Athletes were monitored during a training session for a 24-h long contest. This type of race lasts for 24h, generally starting at 10:00am and ending at 10:00am the following day. Bikers ride as many kilometers as possible on a specific circuit trail in the 24-h period. Athletes are allowed to stop, to sleep, to rest and to eat as much food as they want to eat.

Subjects of the studied group were previously trained to relax by performing DB and concentrating on their breath. These athletes spent 1h (6:30–7:30pm) relaxing performing DB in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. The only activity allowed was reading magazines. Lighting levels were monitored throughout the experiment and did not exceed 15 lux, a level well below that known to influence melatonin secretion [73,74].

As expected, the exercise induced a strong oxidative stress in athletes (Figure 1).

BAP (Biological Antioxidant Potential) levels were determined at different times, before and after exercise. Athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1h relaxing performing DB and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Since this test must be performed several hours after food ingestion, BAP levels were determined pre-exercise at 8:00am before breakfast, at 2:00am, and at 8:00am 24h post-exercise. Values shown are mean ± SD. *P < .05 DB versus control group. **P < .01 DB versus control group.

This study demonstrates that DB reduces the oxidative stress induced by exhaustive exercise. To our knowledge, this is the first study which explores the effect of DB on the stress caused by exhaustive physical activity.

The rationale is as follows (Figure 5)

  1. intense exercise increases cortisol production;
  2. a high plasmatic level of cortisol decreases body antioxidant defenses;
  3. a high plasmatic level of cortisol correlates with a high level of oxidative stress;
  4. DB reduces the production of cortisol;
  5. DB increases melatonin levels;
  6. melatonin is a strong antioxidant;
  7. DB increases the BAP and
  8. DB reduces oxidative stress.

If these results are confirmed in other intense physical activity programs, relaxation could be considered an effective practice to significantly contrast the free radical-mediated oxidative damage induced by intense exercise. Therefore, similar to the way that antioxidant supplementation has been integrated into athletic training programs, DB or other meditation techniques should be integrated into many sports as a method to improve performance and to accelerate recovery.

Hyperventilation, in fact, induces hyperoxia which is known to be related with oxidative stress [81,82]. The hyperventilation syndrome affects 15% of the population and occurs when breathing rates elevate to 21–23 bpm as a result of constricted non-DB. DB can treat hyperoxia and its consequences acting by two synergic ways: restoring the normal breath rhythm and reducing oxidative stress mainly through the increase in melatonin production which is known for its ability to reduce oxidative stress induced by exposure to hyperbaric hyperoxia [83].

Moreover, Orme-Johnson observed greatly reduced pathology levels in regular meditation practitioners [84,85]. A 5 years statistic of approximately 2000 regular participants demonstrated that Transcendental Meditation reduced benign and malignant tumors, heart disease, infectious diseases, mental disorders and diseases of the nervous system. Mourya et al. evidenced that slow-breathing exercises may influence autonomic functions reducing blood pressure in patients with essential hypertension [86]. Finally, there are also evidences that procedures which involve the control of the breathing can positively affect type 2 Diabetes [87], depression, pain [88], high glucose level and high cholesterol [89].

The role of melatonin must also be emphasized. Beyond its antioxidant properties, melatonin is involved in the regulation of the circadian sleep-wake rhythm and in the modulation of hormones and the immune system. Due to its wide medical implications, the increase in melatonin levels induced by DB suggests that this breath procedure deserves to be included in public health improvement programs.

DB increased the levels of melatonin in athletes, and this correlates with lower oxidative stress (ROMs), with lower cortisol levels and with the higher antioxidant status (BAP) in these athletes.

Tooley et al. [46] speculated that meditation-reduced hepatic blood flow [91] could raise the plasma levels of melatonin. Alternatively, since meditation increases plasma levels of noradrenaline [92] and urine levels of the metabolite 5HIAA [93], a possible direct action on the pineal gland could be hypothesized, as melatonin is synthesized in the pineal by serotonin under a noradrenaline stimulus [94]. More likely, we suspect that the increase in melatonin levels determined in our experiment can be mainly attributed to the reduced cortisol levels. Actually, a relationship between cortisol and melatonin rhythms has been observed [95], indicating that melatonin onset typically occurs during low cortisol secretion.

Overall, these data demonstrate that relaxation induced by DB increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol, which is known to negatively affect antioxidant defenses, and the increase in melatonin, a strong antioxidant. The consequence is a lower level of oxidative stress, which suggests that an appropriate recovery could protect athletes from long-term adverse effects of free radicals.