Stikkordarkiv: Betennelser

Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses.

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Denne sammenligner effekten av forskjellige behandlingsformer mot isjas og konkluderer med at f.eks. manipulering, akupunktur og anti-inflammatoriske biologiske midler (renger med dette inkluderer kosttilskudd) er en bedre løsning enn opioider, hvile, treningsterapi, m.m. Den sier også at kirurgi er en god løsning generelt, men ikke for smerte.

http://www.ncbi.nlm.nih.gov/pubmed/24412033

For overall recovery as the outcome, compared with inactive control or conventional care, there was a statistically significant improvement following disc surgery, epidural injections, nonopioid analgesia, manipulation, and acupuncture.

For pain as the outcome, epidural injections and biological agents were significantly better than inactive control, but similar findings for disc surgery were not statistically significant.

The findings support the effectiveness of nonopioid medication, epidural injections, and disc surgery. They also suggest that spinal manipulation, acupuncture, and experimental treatments, such as anti-inflammatory biological agents, may be considered. The findings do not provide support for the effectiveness of opioid analgesia, bed rest, exercise therapy, education/advice (when used alone), percutaneous discectomy, or traction.

The conundrum of sensitization when recording from nociceptors

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Mer fra Geoffrey Bove om nervogene betenneler og nocicepsjon. Denne forholder seg til nocicepsjon som oppstår under måling av nocicepsjon i studier, men har mange interessante poenger. Nevner at noceceptiv sensitering og kontinuerlig nociceptive aktivitet (ongoing activity(OA)) skjer spesielt i betennelsestilstander. Dette er grunnen til at alle med betennelsestilstander i kroppen bør senke betennelsesnivå for å få resultater av behandling.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2854223/

When sensitized, nociceptors often exhibit activity in the absence of apparent or additional stimulation, called ongoing (or spontaneous) activity (OA).

We suggest that there are two types of OA, characterized by their rates. Very slow rates of ongoing activity (<0.2 Hz) are likely to arise from the receptive field and may indicate sensitization during the experiment. Faster rates are likely to arise from the nerve trunk, i.e. the neuritis, or the neuronal cell body.

A key feature of nociceptors is that they develop ongoing activity (OA) when they, or the structures they innervate, are injured or inflamed (Bessou and Perl, 1969; Perl, 1976; Perl, Kumazawa et al., 1976).

To locate RFs, especially in deep tissues, the structures must be stimulated noxiously. Thus, when a slowly conducting neuron is isolated, the peripheral structures from the distal thigh to the toes are stimulated noxiously using fingers or forceps. However, if a mechanical receptive field is not found, another neuron is isolated, and the search repeated. This typically takes dozens of searches over the course of the recording sessions, which in these experiments were 4–7 hours long. In our experiments it was clear that the noxious mechanical stimulus necessary to identify the RFs was in itself sufficient to cause inflammation.

Ongoing activity in sensory elements could be expected to impact the sensory modality of that element. Thus, OA in nociceptors could be expected to lead to the sensation of pain. However, the discharge rate that is necessary to reach perception remains unclear, and definitive studies have not been performed.

Using microneurography in humans, which is similar to the methods reported here, Konietzny et al., reported that electrically evoked nociceptor discharge rates as low at 0.5 Hz could evoke pain (Konietzny, Perl et al., 1981). Another human study reported that while nociceptor discharge under 0.2 Hz usually did not evoke pain, 0.4 Hz usually did (Van Hees and Gybels, 1981), consistent with a similar report (Van Hees and Gybels, 1972). These findings are in general consistent with our findings (Fig. 3). Although it thus remains unknown whether very slow levels of OA are significant for pain, any low rate will release neurotransmitters at their synapses in the spinal cord, which may be extensive due to the high degree of branching of primary afferent neurons to spinal cord neurons.

The trigger point strikes … out!

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En blog av Quinter som bedre forklarer det nevrologiske utgangspunktet for triggerpunkter, eller mer korrekt: ømme punkter og stramme muskler.

Basert på deres nye forklaringsmodell vil et problem (f.eks. betennelse) lenger inn på en sensorisk nerve sender betennelse (nevrogen betennelse) ut til muskelen, i tillegg til at motoriske og sympatiske (stress) signaler fra ryggmargen sendes ut til muskelen og gir en muskelspenning og twitchrespons vi kan se og kjenne med fingrene.

Ang. nevrogen betennelse så nevner wikipedia en studie på mus som viser at magnesium mangel, selv det som er innenfor «normalen» kan bidra til økt utskillelse av SP, som er en nevrogen betennelsesfaktor. http://en.wikipedia.org/wiki/Neurogenic_inflammation

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But when I met the late Bob Elvey, he completely changed my way of thinking about these clinical problems. Bob’s mantra was that “muscles protect nerves.” He introduced me to the dynamics of the nervous system and I came to understand that peripheral nerves of the upper limb had evolved to be able to adapt to the various changes in limb position and length and that they were vulnerable at certain anatomical points along their course.

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In brief, Geoff’s studies have had two major impacts on how we think about pain felt in muscles or other deep structures.

Firstly, he confirmed the presence of nociceptors with multiple receptive fields that branch within the nerve sheaths and extend to other deep tissues (nervi nervorum) [7]. The implication of this finding is that activity in a receptor in one structure such as the nerve sheath, could be perceived in another, such as the muscle.

Secondly, he showed that inflammation of nerves has profound effects on these same axons, the nociceptors to deep structures. These effects include ongoing activity and abnormal mechanical sensitivity [8, and others]. The implication of this finding is that this activity will be perceived by the brain in the area of the receptive fields mapped for the deep structure nociceptors, not in the area of the problem.

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Figure 1. Proposed hypothesis for the development of focal muscle sensitivity and possible alteration in muscle texture with a proximal neural cause. Inflammation affecting a peripheral nerve (red spot) results in spontaneous and mechanically evoked afferent and efferent action potentials in small caliber sensory neurons innervating non-cutaneous structures, and decreased sympathetic discharge (-). These processes may cause reflex motor discharge sufficient to cause a palpable contraction (?), which combined with clinical phenomena associated with neurogenic inflammation (+), could explain the clinical phenomenon that has become known as a “trigger point.”

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Elevated Inflammatory Markers in Response to Prolonged Sleep Restriction Are Associated With Increased Pain Experience in Healthy Volunteers

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Denne nevner at 10 dager med redusert søvn (4 timer) øker betennelsesfaktorer i kroppen. 4 timers søvn er svært lite og de fleste sover nok mer enn dette, men studien nevner at 25% reduksjon (6 timer) også gir en økning i betennelsesfaktorer, dog ikke like kraftig.

Den nederste grafen viser hvordan ubehag i kroppen henger sammen med økning i betennelsesfaktorer.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978405/

Conclusion:

Insufficient sleep quantity may facilitate and/or exacerbate pain through elevations of IL-6. In disorders where sleep disturbances are common, insufficient sleep quantity itself may establish and maintain its co-occurrence with pain and increased inflammation.

Acute sleep loss of up to 3 nights15,17,18 as well as more commonly experienced forms of sleep loss, i.e., sleep reduced by 25%-50% across consecutive days,18,19 have been shown to induce an increase of interleukin-6 (IL-6) and C-reactive Protein (CRP) levels. In addition, increased levels of IL-6 have been found in patients suffering from primary insomnia.20,21

Pain is a hallmark of inflammatory processes. Prostaglandins, in particular PGE2, are classical pain mediators, but in the last decade a variety of novel pain modulators have been identified. For example, proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) have been found to be potent pain-inducing and pain-facilitating agents, able to sensitize primary sensory neurons.26

Ten days of sleep restriction to 50% of the habitual time led to an IL-6 increase of 1.16 pg/mL in the current study. Sleep restriction to approximately 25% of usual sleep time over one week has been found to lead to a slightly smaller IL-6 increase of 0.75 pg/mL compared to the present result.19 This may suggest a dose-response relationship between chronicity/severity of sleep restriction and elevation of IL-6 levels, and warrants further investigation.

Informasjon om Palmitoyletanolamide

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Palmitoylethanolamide (PEA) er et svært interessant produkt som har mye forskning bak seg, men er svært lite kjent og lite tilgjengelig. I Italia, Spania og Tyskland selges det som «mat til medisinsk formål», mens i Nederland selges det som kosttilskudd, men da uten noen påstander knyttet til produktet.

Det kan bestilles fra Nederland her: http://www.rs4supplements.com/en/peapure-capsules-info

PEA er et naturlig fettstoff som kroppen produserer selv. Det finnes i mange matvarer, særlig i kjøtt, egg, soyabønner og andre peanøtter.

Kroppen produserer PEA spesielt ved betennelsestilstander, og man ser det øker i konsentrasjon lokalt der betennelsen er. PEA har en beskyttende rolle i en betennelsestilstand. Men om betennelsestilstandende vedvarer kan kroppens naturlige PEA brukes opp. Da får man mindre beskyttelse og det blir lettere å få andre plager eller vedvarende plager. Siden det er kosttilskudd må man regne med å bruke minst 2-3 måneder for å se om det hjelper.

PEA gjør at kroniske betennelsesreaksjoner lettere kan brytes slik at regenerering kan inntre igjen. PEA er spesielt interessant fordi det virker på nervetråder. Nevropati (ødelagte nervetråder) er en svært vanskelig tilstand å behandle, men PEA har potensiale til å være både et effektivt og bivirkningsfri tilskudd for å starte regenereringen av nervetråder. PEA er et endokannabinoid-lignende stoff. Man får alle de medisinske og smertedempende effektene lik kannabinoider, men uten noen form for rus.

Her er en lang rekke med studier som har blitt gjort på nevropati og PEA:

Micronized palmitoylethanolamide reduces the symptoms of neuropathic pain in diabetic patients. (Free in PMC)

These results suggest that PEA-m could be considered as a promising and well-tolerated new treatment for symptomatology experienced by diabetic patients suffering from peripheral neuropathy.

Chronic idiopathic axonal neuropathy and pain, treated with the endogenous lipid mediator palmitoylethanolamide: a case collection. (Free in PMC)

In all these patients, PEA reduced pain significantly, without side effects. PEA can be administered in addition to other analgesics, without negative drug-drug interactions, or can be used as a stand-alone analgesic. Due to a favorable ratio between efficacy and safety, PEA should be considered more often as a treatment for neuropathic pain.

Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy: pain relief and neuroprotection share a PPAR-alpha-mediated mechanism. (Free in PMC)

These results strongly suggest that PEA, via a PPAR- α -mediated mechanism, can directly intervene in the nervous tissue alterations responsible for pain, starting to prevent macrophage infiltration.

Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. (Free in PMC)

Probably due to the fact that PEA is an endogenous modulator as well as a compound in food, such as eggs and milk, no serious side effects have been reported, nor have drug-drug interactions.

Palmitoylethanolamide restores myelinated-fibre function in patients with chemotherapy-induced painful neuropathy.

In a severe condition such as painful neuropathy associated with multiple myeloma and chemotherapy, a safe substance such as PEA provides significant restoration of nerve function.

Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist.

The data support the hypothesis of protection against inflammatory and neuropathic pain by PEA.

Palmitoylethanolamide in CNS health and disease.

Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis.

Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain.

Collectively, the findings presented here propose that palmitoylethanolamide merits further consideration as a disease-modifying agent for controlling inflammatory responses and related chronic and neuropathic pain.

Mast cells, glia and neuroinflammation: partners in crime?

N-Palmitoylethanolamine has proven efficacious in mast-cell-mediated experimental models of acute and neurogenic inflammation.

Her er en rekke studier som har blitt gjort på betennelser og PEA:

Gastric bypass in morbid obese patients is associated with reduction in adipose tissue inflammationvia N-oleoylethanolamide (OEA)-mediated pathways.

Palmitoylethanolamide regulates development of intestinal radiation injury in a mast cell-dependent manner.

Palmitoylethanolamide normalizes intestinal motility in a model of post-inflammatory accelerated transit: involvement of CB₁ receptors and TRPV1 channels.

Palmitoylethanolamide inhibits rMCP-5 expression by regulating MITF activation in rat chronic granulomatous inflammation.

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice.

An apPEAling new therapeutic for ulcerative colitis?

Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation.

A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury.

Glia and mast cells as targets for palmitoylethanolamide, an anti-inflammatory and neuroprotective lipid mediator.

New insights in mast cell modulation by palmitoylethanolamide.

Nutritional essentiality of sulfur in health and disease.

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Denne beskriver det aller meste om svovel og hvorfor det er et viktig næringsstoff å fokusere på. Den nevner bl.a. at svovel tilskudd, f.eks. MSM, går inn i TBS (total body sulfur pool) som en svovelkilde for glutation. Sammen med metionin og cystein fra maten.

Den nevner også hvordan stress og betennelser skaper en større «turnover» av proteiner, som ofte ikke samsvarer med inntaket av proteiner. Man blir da kronisk på underskudd av svovel og proteiner. Dette forklarer hvorfor proteintilskudd er viktig ved betennelsestilstander og stress tilstander som f.eks. kronisk smerte.

Svovel og Nitrogen har et forhold på 1:14 og er tett sammenkoblet. Når nitrogen forsvinner forsvinner også svovel. Muligens kan man måle svoveltilgjengeligheten i kroppen ved å måle nitrogen med urinstix.

http://www.ncbi.nlm.nih.gov/pubmed/23815141

Hele artikkelen er i min dropbox.

HYPERHOMOCYSTEINEMIA AS A RESPONSE TO STRESS

N and S maintain tightly correlated ratios in tissues of both healthy subjects8 and diseased patients.167 Acute stressful conditions of any cause unleash a shower of many cytokines that fulfill a myriad of autocrine, para- crine, and endocrine functions.168 As a consequence, enhanced tissue proteolysis throughout the body ensues, allowing the redirection of AA residues toward the pref- erential overproduction of acute-phase reactants and repair proteins by the liver and at the site of injury.169 The rate of protein degradation usually exceeds that of protein undergoing neosynthesis,170,171 leading to a negative N balance with subsequent depletion of TBN reserves. The increased urinary excretion of N catabolites (mainly urea, but also creatinine, NH4+, 3-CH3-histidine, and other minor compounds) demonstrates that both metabolic and structural tissues participate in the adap- tive responses to injury in proportion to the magnitude of initial impact.31,170,171 In very aggressive conditions (burns) affecting adult men, urinary output of N may be as high as 250 g of N per week, which corresponds to a loss of 6–7 kg of LBM31 or 12–14% of metabolically active tissues.30 Major stressful disorders are associated with massive urinary excretion of S,167,172 which depletes endogenous pools of TBS. In stressors of medium severity (bone fracture), S spillover has been estimated to be 17 g of S per week, or more than 10% of TBS body stores. Interestingly enough, measurement of S and N urinary losses yields values very close to the 1:14 ratio that char- acterizes mammalian tissues,8,167 indicating that TBN and TBS pools exhibit concomitant degradation patterns throughout the course of injury.

Heart rate variability biofeedback: how and why does it work?

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Bekrefter alle elementer jeg jobber med i Autonom pust: vagus, betennelse, m.m.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104929/

In recent years there has been substantial support for heart rate variability biofeedback (HRVB) as a treatment for a variety of disorders and for performance enhancement (Gevirtz, 2013). Since conditions as widely varied as asthma and depression seem to respond to this form of cardiorespiratory feedback training, the issue of possible mechanisms becomes more salient. The most supported possible mechanism is the strengthening of homeostasis in the baroreceptor (Vaschillo et al., 2002; Lehrer et al., 2003). Recently, the effect on the vagal afferent pathway to the frontal cortical areas has been proposed. In this article, we review these and other possible mechanisms that might explain the positive effects of HRVB.

ANTI-INFLAMMATORY EFFECTS

It is known that the vagal system interacts closely with the inflammatory system, such that increases in vagus nerve traffic (usually produced by electrical vagal stimulation) are associated with decreases in serum levels of various inflammatory cytokines (Borovikova et al., 2000; Tracey, 2002). One study did find a decrease in C-reactive proteins among hypertensive patients treated with HRV biofeedback (Nolan et al., 2012). In another study, we experimentally exposed healthy subjects to an inflammatory cytokine, lipopolysaccharide (Lehrer et al., 2010). Usually both sympathetic and parasympathetic activity is blocked by lipopolysaccharide. Although no biofeedback-induced decreases in inflammatory cytokines were found, the autonomic effects of inflammation were greatly modulated, indicating that a greater resiliency was preserved among individuals given HRV biofeedback.

Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans

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Denne viser hvordan selv de uten diabetes får økt cytokinverdi (betennelse) i blodet i 1-2 timer etter blodsukkerstigning. I denne studien var det snakk om blodsukker over 15 mmol/L. De sier at blodsukker økninger påvirker cytokinnivået mer enn et stabilt høyt blodsukker.

http://circ.ahajournals.org/content/106/16/2067.full

Control Subjects:

Plasma IL-6 levels rose from a basal value of 2.0±0.7 pg/mL to a peak of 3.1±0.9 pg/mL at 1 hour (P<0.01) and returned to basal level at 3 hours (Figure 2).

Fasting plasma TNF-α levels were 3.3±1.2 pg/mL; they peaked at 1 hour (4.9±1.4 pg/mL, P<0.01), and returned to baseline at 3 hours.

Plasma IL-18 levels rose from a basal value of 116±28 pg/mL to a peak of 140±31 pg/mL at 2 hours (P<0.01) and returned to basal levels at 3 hours (110±26 pg/mL).

The novel findings of the present study were that (1) acute hyperglycemia in control and in IGT subjects induces an increase in plasma IL-6, TNF-α, and IL-18 concentrations; (2) the effect of sustained hyperglycemia is reproduced by transient oscillations in plasma glucose and is amplified by the IGT status; and (3) the antioxidant glutathione completely prevents the rise in plasma cytokines induced by hyperglycemia. These results indicate that hyperglycemic spikes affect cytokine concentrations more than continuous hyperglycemia, at least in the short term, and suggest that an oxidative mechanism mediates the effect of hyperglycemia.

Another finding of the present study was that glutathione, a powerful antioxidant, completely prevented cytokine increase induced by oscillatory hyperglycemia in healthy humans. Hyperglycemia-induced oxidative stress, 32 along with soluble advanced glycation end products and products of lipid peroxidation, possibly serves as a key activator of upstream kinases, leading to induction of inflammatory gene expression.33

Inflammation-induced hyperalgesia: Effects of timing, dosage, and negative affect on somatic pain sensitivity in human experimental endotoxemia.

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En studie til som bekrefter at lav-grads betennelse gir hyperalgesi, altså økt smerteopplevelse.

http://www.ncbi.nlm.nih.gov/pubmed/24814500

Abstract

BACKGROUND:

Inflammation-induced pain amplification and hypersensitivity play a role in the pathophysiology of numerous clinical conditions. Experimental endotoxemia has recently been implemented as model to analyze immune-mediated processes in human pain. In this study, we aimed to analyze dose- and time-dependent effects of lipopolysaccharide (LPS) on clinically-relevant pain models for musculoskeletal and neuropathic pain as well as the interaction among LPS-induced changes in inflammatory markers, pain sensitivity and negative affect.

METHODS:

In this randomized, double-blind, placebo-controlled study, healthy male subjects received an intravenous injection of either a moderate dose of LPS (0.8ng/kg Escherichiacoli), low-dose LPS (0.4ng/kg), or saline (placebo control group). Pressure pain thresholds (PPT), mechanical pain sensitivity (MPS), and cold pain sensitivity (CP) were assessed before and 1, 3, and 6h post injection to assess time-dependent LPS effects on pain sensitivity. Plasma cytokines (TNF-α, IL-6, IL-8, IL-10) and state anxiety were repeatedly measured before, and 1, 2, 3, 4, and 6h after injection of LPS or placebo.

RESULTS:

LPS administration induced a systemic immune activation, reflected by significant increases in cytokine levels, body temperature, and negative mood with pronounced effects to the higher LPS dose. Significant decreases of PPTs were observed only 3h after injection of the moderate dose of LPS (0.8ng/kg). MPS and CP were not affected by LPS-induced immune activation. Correlation analyses revealed that decreased PPTs were associated with peak IL-6 increases and negative mood.

CONCLUSIONS:

Our results revealed widespread increases in musculoskeletal pain sensitivity in response to a moderate dose of LPS (0.8ng/kg), which correlate both with changes in IL-6 and negative mood. These data extend and refine existing knowledge about immune mechanisms mediating hyperalgesia with implications for the pathophysiology of chronic pain and neuropsychiatric conditions.