It has been widely shown that neuropathic pain to include significant changes in spinal support cells called Microglia. Now it’s been shown that “newly identified CD11c-positive microglia as a subset that increases during the remission phase of neuropathic pain”.
Jeff Mogil’s group in McGill has shown that although inflammation is involved in development of pain, there are inflammatory neutrophil leukocytes that protect against development of chronic pain.
Blanket treatments against Microglia or White Blood Cell inflammation might be coounterproductive
Microglia:
Tsuda M, Kohno K.
[Neuropathic pain decoded by microglial heterogeneity].
Nihon Yakurigaku Zasshi. 2023;158(5):362-366
https://pubmed.ncbi.nlm.nih.gov/37673611/
- spinal microglia”lead to an increase in the excitability of pain-transmission neural pathway” and facilitate neuropathic pain
- yet CD11c-positive microglia facilitate remission from neuropathic pain
Tissue Neuroinflammation:
Parisien, Marc, et al.
Acute inflammatory response via neutrophil activation protects against the development of chronic pain.
Science Translational Medicine 14.644 (2022): eabj9954
- Tissue injury involves considerable neural inflammation.
- In the course of this inflammation, a specific subgroups of neutrophils is involved in nerve repair
- anti-inflammatory NSAIDS interfere with this and are linked to more chronic back pain and TMJ. Diclofenac (Voltaren) seems to be the worst.
Comment – drugs altering microglia or WBC inflammation need to used with caution.
Instead of using NSAIDs in acute pain, one article suggested either acetaminophen (useless in back pain), tramadol or opioids.
Sisignano, Marco, and Gerd Geisslinger.
Rethinking the use of NSAIDs in early acute pain.
Trends in Pharmacological Sciences (2023)
Science & Society| Volume 44, ISSUE 4, P193-195, April 202
https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(23)00016-0
Tramadol is not on our drug pain (unaffordable to poor)and doctors have been so much bullied by our College, they refuse to use opioids.
Patients in acute pain are screwed.
Addendum:
Another cell type hitting the spotlight are Killer T cells
Kim, Hyoung Woo, et al.
The therapeutic potential of natural killer cells in neuropathic pain.”
Trends in Neurosciences (2023) in press.
https://drive.google.com/file/d/1KXAKwiXT2GvB39ygOVj5kc7mcwjoYrT5/view
- The make a good case for benefits of NK (natural killer) cells
- However
- ” For example, the efficacy of intravenous immunoglobulin (IVIg) treatment in patients with chronic inflammatory neuropathy has been associated with suppression of NK cell cytotoxicity [78–81].”
78. Bohn, A.B. et al. (2011) The effect of IgG levels on the number of natural killer cells and their Fc receptors in chronic inflammatory demyelinating polyradiculoneuropathy. Eur. J. Neurol. 18, 919–924
79. Heming, M. et al. (2019) Immune cell profiling of the cerebrospinal fluid provides pathogenetic insights into inflammatory neuropathies. Front. Immunol. 10, 515
80. Mausberg, A.K. et al. (2020) NK cell markers predict the efficacy of IV immunoglobulins in CIDP. Neurol. Neuroimmunol. Neuroinflamm. 7, e884
81. Fujioka, T. et al. (2000) Flow cytometric analysis of infiltrating cells in the peripheral nerves in experimental allergic neuritis.
J. Neuroimmunol. 108, 181–191
“These findings suggest either the potential role for NK cells in disease etiology or that IVIg may achieve its benefit by conversion of NK cells to an inflammation-resolving phenotype [82]”
82. McAlpine, S.M. et al. (2021) High dose intravenous IgG therapy modulates multiple NK cell and T cell functions in patients with immune dysregulation. Front. Immunol. 12, 660506