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INCREASED INTERSTITIAL CONCENTRATIONS OF PYRUVATE AND LACTATE IN THE TRAPEZIUS MUSCLE OF PATIENTS WITH FIBROMYALGIA: A MICRODIALYSIS STUDY

Om at fibromyalgi innebærer høyere grad av melkesyre i musklene, og at dette er en av bidragene til den kroniske smerten.

http://www.medicaljournals.se/jrm/content/?doi=10.2340/16501977-0581&html=1

«There was a significant group effect (p = 0.039) with higher interstitial lactate concentrations in FMS compared with CON (Fig. 2a).»

«There was a highly significant difference in interstitial concentration of pyruvate (p < 0.001) between the 2 groups; the concentrations were higher among the FMS patients (Fig. 2b).»

«One possible explanation for the higher [pyruvate] in FMS of the present study is changes in the lactate-pyruvate metabolism via lactate dehydrogenase isoforms (18). Another alternative is that a reduction in tissue oxygenation in FMS (8) may result in higher [pyruvate] due to a shift towards an anaerobic state. Such a circumstance might also cause the significantly higher [lactate].»

«The aerobic capacity of the muscle is largely governed by the number of mitochondria and their enzymes (20). Lindh et al. reported lower capillary density and enzymes associated with aerobic metabolism in FMS (21); however, it is unknown if a general deconditioning in FMS involves the postural trapezius. The mitochondrial density increases as result of exercise (see (22) for references) and affects the level of metabolites (i.e. enhanced aerobic capacity).»

«Lactate is also involved in peripheral nociception, and it appears to facilitate the response of acid-sensing ion channel 3 (ASIC-3) to low pH (26). Such ASIC channels are considered as molecular transducers for nociception and mechanosensation (26).»

«It has been reported that FMS has abnormal cardiovascular responses to low-grade mental stress (35). Several studies indicate altered sympathetic activation in FMS (36–39), which in turn may affect [lactate] (40). Sympathetic activation may also cause decreased blood flow even without hypoxia (26, 41).»

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The effects of slow breathing on affective responses to pain stimuli: an experimental study.

Viktig studie om pustens regulering av smerte som nevner at å senke pustefrekvens demper smerte betraktelig for frisk mennesker, men hos Fibromyalgi er det ikke nok i seg selv som smertedemping.

http://www.ncbi.nlm.nih.gov/pubmed/20079569

Dropbox link: https://dl.dropboxusercontent.com/u/17457302/Forskning%20mappe%20for%20terapi/STUDIE%20-%20The%20effect%20of%20slow%20breathing%20on%20affective%20responses%20to%20pain%20stimul.pdf
Dropbox link til kommentar om fibromyalgi: https://dl.dropboxusercontent.com/u/17457302/Forskning%20mappe%20for%20terapi/Respiration-induced%20hypoalgesia%20-%20%20Additional%20evidence%20for%20pain%20modulation%20deficits%20in%20fibromyalgia.pdf

«M and HC were exposed to low and moderate thermal pain pulses during paced breathing at their normal rate and one-half their normal rate. »

«Participants who reported higher levels of trait positive affect prior to the experiment showed greater decreases in negative affect as a result of slow versus normal breathing.  »

«FM patients and normal controls were instructed to breathe at either their normal rate or 1/2 that rate during four blocks of four trials.  »

«An inspection of resting breathing rates for the two groups revealed no differences between groups: an average rate of 13.68 (SD = 3.54) breaths per minute for FM patients, and 13.63 (SD = 2.17) for HCs.  »

Skjermbilde 2013-05-12 kl. 11.31.28

«These findings are consistent with those of an observational investigation, which found lower breathing rates were associated with reduced pain intensity and unpleasant- ness ratings when participants meditated while receiving pulses of painful heat [12]. »

«Since all participants were administered trials where pain was administered, the potential benefit of interventions that include the practice of meditation in the treatment of pain patients is sup- ported. However, the mixed findings for FM patients give us pause. It may be more difficult to engender states of relaxation needed to endure pain in FM patients through slow paced breathing alone. »

«Taken together these findings are consistent with the model of pain as a homeostatic emotion. In this model, the neurophysiologi- cal processes that underlie how slow breathing influences pain begins with the increased bronchiopulmonary afferent activity. This activity produces increased activation in the left mid-insula and anterior insula [24], as well as increased activation in the left anterior cingulate associated directly with increased heart rate variability [18], corresponding with a shift in sympathovagal tone. This activation counterbalances the acute activation in the right anterior insula produced by painful stimulation [2] by virtue of opnent interaction [4].»

«The findings indicate that a slower breathing rate is a useful target in interventions for patients in pain. Reductions in pain and negative affect may be ex- pected when people are guided to halve their respiration rate.  »

«However, for FM patients, the data suggest that med- itative breathing alone is insufficient. Clinical interventions that address positive affective disregulation, appear necessary to assist FM patients in the management of their chronic pain. «

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Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia

Nevner at ved 50% mindre oksygen så kommer en type stamceller ut, MSC, som kan bli skjelett, blodkar og fettceller. Men å få 50% mindre oksygen ved pusteteknikker er svært vanskelig. Ved 4000 moh kan vi få det til om vi er der lenger enn 3 uker, slik som musene i denne studien.

http://onlinelibrary.wiley.com/doi/10.1634/stemcells.2006-0164/full

«Hypoxia-induced mobilization appears to be specific for MSCs since total circulating hematopoietic progenitor cells were not significantly increased»

«Certain stem cells are able to exit their production site, circulating into blood before reseeding their target tissues. In the case of hematopoietic stem cells (HSCs), such circulation is essential during development since they migrate from one site to the next (embryonic aorta-gonad-mesonephros region, fetal liver, adult bone marrow).»

«Adult male Wistar rats (7 weeks, 220 g; Harlan, Gannat, France, http://www.harlan.com) were housed for 3 weeks in a hypoxic chamber (50 kPa), which caused chronic hypoxia, as previously described [27], and were compared with matched control rats housed in normoxic conditions (101 kPa). «

Viser hvor mye stamceller som er i blod (PBH) i hypoxi (50 kPa) relativt til normoxi (PBN – 101 kPa)

«In conclusion, we report that few MSCs circulate in the PB under stationary conditions in rats. Large amounts of MSCs can be mobilized (an increase of almost 15-fold) under hypoxic conditions. These data demonstrate that MSCs can be mobilized into the PB via stimuli distinct from those involved in hematopoietic stem cell mobilization.»

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Hypoxia: Are stem cells in it for the long run?

Om stamceller og at hypoxi og HIF-a er viktig for deres overlevelse og funksjon.

http://www.landesbioscience.com/journals/cc/article/14535/

«tudies by others over the past 10 years has also indicated that hypoxia and Hif expression are essential for self-renewal and are involved in the regulation of proliferation for some types of stem cells. «

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Aerobically generated CO2stored during early exercise

Beskriver hvordan CO2 lagres i kroppen under trening og bidrar til bikarbonat buffer kapasitet.

http://jap.physiology.org/content/87/3/1048.long

«Over a similar time frame, the femoral vein blood pH and plasma K+ and Formulaconcentrations increase without an increase in Formula. Thus CO2 from aerobic metabolism is converted toFormularather than being eliminated by the lungs.»

«We conclude that a major component of the aerobically generated increase in CO2 stores is the newFormulagenerated as phosphocreatine is converted to creatine.»

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Physiological mechanisms dissociating pulmonary CO2 and O2 exchange dynamics during exercise in humans

Beskriver hvordan forholdet mellom CO2 og O2 endrer seg unde trening, og spesielt over melkesyreterskel hvor bikarbonat også begynner å spille inn i homeosasen av pH i blod.

http://ep.physoc.org/content/92/2/347.long

«During incremental exercise, the increased rate of Graphic relative to pulmonary O2 uptake (Graphic) can be used to quantify θL validly if aerobic and hyperventilatory sources can be ruled out, i.e. θL is then attributable to the decrease in muscle and blood [HCO3]. In many cases, however, very rapid incrementation of work rate and/or prior depletion of CO2 stores (by volitional or anticipatory hyperventilation) can yield a ‘false positive’ non-invasive estimation of θL(‘pseudo-threshold’) resulting from a slowing of the rate of wash-in of transient CO2stores.»

«Since the tissue capacitance for CO2 is appreciably greater than for O2 (Farhi & Rahn, 1955), this means that the respiratory exchange ratio (R), i.e. the ratio of the volumes of CO2and O2 exchanged across the tissue of interest per unit time, will differ from that of the respiratory quotient (RQ), i.e. the ratio of the amounts of metabolic CO2 and O2 produced and consumed, respectively, by the tissue per unit time not only across the lung, where it is most typically determined and from which inferences are most typically drawn, but also across the muscle vascular bed itself. »

«But, in addition, skeletal muscle contraction results in a transient metabolic alkalosis in the force-generating units (Steinhagen et al. 1976; Kemp, 2005) and in the venous effluent of the exercising muscle (Wasserman et al. 1997) as a result of the net proton (H+) trapping associated with the high-energy phosphate utilization, i.e. H+ release as ATP is split, and H+ uptake consequent to phosphocreatine (PCr) splitting (Kushmerick, 1997).»

«This transient alkalosis therefore results in a component of the metabolically produced CO2 being retained within the muscle.»

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Lactic acid buffering, nonmetabolic CO2 and exercise hyperventilation: a critical reappraisal

Om non-metabolic CO2, altså CO2 som ikke skapes i mitokondriene men kommer fra bikarbonat-reaksjoner med melkesyre.

www.ncbi.nlm.nih.gov/pubmed/15890562‎
Hele studien i dropbox: https://dl.dropboxusercontent.com/u/17457302/Nonmetabolic_CO2.pdf

«It has been suggested that hyperventilation and the disproportionate increase in VCO2 versus VO2 above the ventilatory threshold (V(TH)) in ramp exercise are due to the production of nonmetabolic CO2 in muscle because of lactic acid buffering by plasma bicarbonate entering the cell in exchange with lactate»

«(1) bicarbonate is not the main buffer in the muscle; (2) the decrease in standard bicarbonate concentration is not the mirror image of the increase in lactate concentration; (3) buffering by bicarbonate does not increase CO2 production in muscle (no nonmetabolic CO2 is produced in tissues); (4) the CO2 flow to the lungs, which should not be confused with VCO2 at the mouth, does not increase at a faster rate above than below V(TH).»

Forklaring på Non-Metabolic CO2 her:

Non-Metabolic Carbon Dioxide

At rest and during moderate exercise, lactic acid will not increase in your muscles because all that is produced is also used. Once you reach more challenging work rates, production exceeds use and the acid enters your blood. To maintain a healthy pH, sodium bicarbonate in your blood buffers most lactic acid by breaking it down to water and carbon dioxide. This results in additional carbon dioxide that must be released by your blood.

Read more: http://www.livestrong.com/article/524672-what-effect-does-exercise-have-on-the-amount-of-carbon-dioxide-released-by-the-blood/#ixzz2SmWggmYh

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Relationship between Hyperventilation and Excessive CO2 Output during Recovery from Repeated Cycling Sprints

Nevner at CO2 ikke er årsak til hyperventillering under trening, men at det er melkesyre. Pusten øker for å fjerne CO2 så syreoverskuddet holdes i balanse.

http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/51990/1/repeat-ex-PR.pdf

«During incremental exercise, blood lactate is progressively increased above the VT. This is buffered by the bicarbonate system. This results in progressive reduction of blood bicarbonate ion (Beaver et al. 1986a) and metabolic acidosis. In order to improve this metabolic acidosis, ventilation is driven and becomes hyperventilation above the VT in incremental exercise. As a result, Vco2excess is progressively increased above the VT.»

«The following findings suggest that hyperventilation in exercise is induced by metabolic acidosis due to an increase in blood lactate detected by peripheral chemoreceptors. »

«Secondly, it was found that intravenous infusion of bicarbonate during incremental exercise attenuated the decrease in blood pH above the VT and consequently reduced hyperventilation by 15-30 % (Peronnet et al. 2007). However, if this hyperventilation accompanies a decrease in Paco2, it would stimulate central chemoreceptors and peripheral receptors via its effect on pH (Clement et al. 1992) and consequently can attenuate the hyperventilation. »

«Thus, hyperventilation during second recovery did not increase despite an increase in blood lactate probably due to lower Paco2 than that during first recovery. »

«During recovery, lactate is not produced in muscle. However, lactate is transported from the muscle to blood. The buffering system is primarily a non-bicarbonate system in muscle cells (Hultman and Shalin, 1980) but a bicarbonate system in blood (Yano 1987, Peronnet and Aguilaniu 2006).»

«After the end of heavy, very heavy and cycling sprint, Paco2 becomes lower than the resting level (Kowalchuk et al. 1988, . Stringer et al. 1992). »

 

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painDETECT

Online spørsmålskjema som viser om smertene kommer fra nevropati eller ikke.

Klikk for å få tilgang til painDETECT-Questionaire-01.pdf

Denne Studien viser helel 88% sikkerhet som diagnoseverktøy: http://www.ncbi.nlm.nih.gov/pubmed/17022849

«Simple, patient-based, easy-to-use screening questionnaires can determine the prevalence of neuropathic pain components both in individual LBP patients and in heterogeneous cohorts of such patients.»

«The PD-Q is a reliable screening tool with high sensitivity, specificity and positive predictive accuracy; these were 84% in a palm-top computerised version and 85%, 80% and 83%, respectively, in a corresponding pencil-and-paper questionnaire.»

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Human Physiology Respiration

Grunnleggende gjennomgang av pustefunksjon, med god informasjon om både O2 og CO2 og deres partialtrykk, og mange informative animasjonsvideoer. Nevner bl.a. at trening ikke øker pustefrekvens pga CO2, men andre faktorer som stresshormoner, aktivitet, kroppstemperatur.

http://people.eku.edu/ritchisong/301notes6.htm

Heavy exercise ==> greatly increases respiratory rate

Mechanism?

  • NOT increased CO2
  • Possible factors:
    • reflexes originating from body movements (proprioceptors)
    • increase in body temperature
    • epinephrine release (during exercise)
  • impulses from the cerebral cortex (may simultaneously stimulate rhythmicity area & motor neurons)