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LPS (endotoxins) Kills Pain

Discussion in 'Scientific Studies' started by ecstatichamster, Dec 4, 2018.

  1. ecstatichamster

    ecstatichamster Member

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    Nov 21, 2015
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    https://www.sciencedirect.com/science/article/pii/0006899394919089

    Abstract
    Activation of the immune system in response to either infection or lipopolysaccharide (LPS) produces neurophysiological, neuroendocrine and behavioral changes. Some of the physiological consequences of LPS are mediated by endogenous opioid peptides.

    The following studies were designed to characterize the effects of LPS in several behavioral paradigms, and to determine the role of opioids in mediating these effects. The effects of LPS on locomotor and self-care activity were assessed in the open field test.

    Rats were injected with either saline or a dose of LPS (25, 50, 100, or 1000 μg/kg). 4 h later, the animals were placed in an open field and the numbers of line crossings, rearings and grooming episodes were counted.

    LPS significantly suppressed the three open field behaviors in a dose-related manner. The effect of LPS on sensitivity to pain was determined using the hot-plate and tail-flick tests.

    Administration of LPS (200 μg/kg) increased pain sensitivity in the hot plate test 30 min after drug administration, but produced a significant analgesic response 4 h after drug administration in both tests. Further characterization of LPS-induced analgesia demonstrated that it began about 2 h after and disappeared 30 h after the administration of LPS.

    Administration of naltrexone completely blocked the analgesic effects of LPS 4 h after its administration, but had no effect on LPS-induced suppression of activity in the open field. The effect of LPS on body temperature was biphasic, producing hypothermia at 2 h and hyperthermia at 8–30 h after its administration. Naltrexone had no effect on the body temperature changes induced by LPS. These results suggest that endogenous opioids mediate the analgesic effects of LPS, but they are involved neither in mediating LPS-induced suppression of locomotor and self care behaviors nor in alterations of body temperature.
     
  2. paymanz

    paymanz Member

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    Very interesting
     
  3. tonto

    tonto Member

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    Nov 29, 2014
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    Nice article... this may be why we crave what we are "allergic" to. Or, eating junk food helps alleviate pain by endotoxin production.
     
  4. Lejeboca

    Lejeboca Member

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    Jun 19, 2017
    Messages:
    110
    As I understand it, the opioids were produced in response to LPS and, while mitigating the effects of LPS on CNS, they also alleviated the pain once they've kicked in.

    Visceral Inflammation and Immune Activation Stress the Brain

    " Neuropeptide Y (NPY) signaling via Y2 and Y4 receptors has in particular been implicated in the short-and long-term behavioral effects of peripheral immune challenge. Thus, Y2 receptor knockout mice are particularly sensitive to the effects of LPS-evoked immune stress to attenuate locomotion and social interaction and to increase anxiety-like behavior, while the LPS-induced rise of circulating corticosterone is suppressed by Y2 receptor knockout (8, 98, 99). Furthermore, knockout of Y2 and Y4 receptors unmasks the ability of a single LPS injection to cause a delayed and prolonged increase in depression-like behavior, which indicates that NPY signaling conveys resilience to some of the adverse effects of immune stress on the brain (98). "

    Also from the reference above:
    "While most information on the cerebral impact of PAMP/MAMP-evoked immune stimulation has been derived from animal studies, select microbial metabolites, such as LPS, have also been tested in humans. For instance, intravenous LPS injection in healthy human volunteers increases the circulating levels of IL-6, IL-10, TNF-α, soluble TNF receptor, IL-1 receptor antagonist, and cortisol, which is associated with enhanced body temperature, anxiety, negative mood, decreased memory performance, and hyperalgesia (8790). While these effects are similar to those observed in rodents, the potency of LPS in terms of dose per body weight is >100 times higher in humans (88). Mechanistic studies have shown that the sickness response elicited by intravenous LPS injection in healthy male humans is associated with microglial activation throughout the brain as observed by positron emission tomography (91)."
     
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