Pain and Depression – Consider Brain Inflammation With Tumor Necrosis Factor (TNF) – and What About Brain Aging


Prior, I published a belief that depression in some cases was a manifestation of chronic pain for which ketamine could temporarily block.


In this 21 page article they make clear connections between brain cytokine inflammation especially TNF (Tumor Necrosis Factor), chronic pain, and depression. The Hippocampus seems to be the center of much of this. Treatments directed against brain inflammation include antidepressants and interspinal entanercept. Poor sleep prevents clearance of inflammatory compounds from brain. Exercise is an anti-inflammatory. Sensitized Glial cell in the hippocampus generate these chamicals.

Neurosci Biobehav Rev. 2015 Apr 7. pii: S0149-7634(15)00088-3. doi:
10.1016/j.neubiorev.2015.03.014. [Epub ahead of print]
The hippocampus and TNF: Common links between chronic pain and depression.
Fasick V(1), Spengler RN(2), Samankan S(1), Nader ND(3), Ignatowski TA(4).

  • Pro-inflammatory brain compounds seen in chronic pain and in depression
  • Hippocampal TNF appear important mediator
  • TNF inhibits Norepinephrine secretion, deficiency of which related to both depression and neuropathic pain
  • Damage induced by high glucocorticoid levels may stimulate cytokine/TNF production. Depression is associated with Hippocampal damage and scrinkage.
  • Antidepressants (Tricyclic, serotonin, and NE-serotonin reuptake inhibitors) -increase the availability of monoamines
    -regulates the production of cytokines, such as TNF
    – mediates an increase in hippocampal neurogenesis

Neuroinflammation in the aging hippocampus is mediated by microglial cells:

Neuroinflammation in the normal aging hippocampus
Neuroscience In Press, March 2015
R.M. Barrientos, M.M. Kitt, L.R. Watkins, S.F. Maier

  • sensitized microglial cells are at the centre of aging neuroinflammation
  • Peripheral inflammation can trigger central “Interleukin-1 beta (IL-1 b ), a pro-inflammatory cytokine, is a principal player in this cascade. As part of its role in this response, IL-1 b enhances T and B lymphocyte proliferation and stimulates natural killer cell cytocidal activity to eliminate the injured cells or invading pathogen. IL-1 b also induces the production of other cytokines from many cell types such as tumor necrosis factor-alpha (TNF- a ), and interleukin-6 (IL-6), which in turn have secondary effects on other cells”

microglial_inhibitionSadly, It misses the pro-inflammatory consequences of inadequate sleep. Elderly, with sleep disordered breathing, suffer cognitive decline and need attention with sleep apnea measures.

The new kid on the block is interspinal etanercept injections. I give it with a 1″ – 27 gauge needle¬† – given in between cervical spinous process with head down(over edge of a bed) for 5 minutes. I have tried it and finds it does clear one’s head and improve mood but is $200 a bottle. In low back radiculitis, it took 2 shots 1-2 weeks apart to clear out TNF… cgdoudounes cgdoudounes

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