Wisdom Wednesday: Cytokine-mediated Inflammation and Neuropathy from Metabolic Syndrome

Painful neuropathy (PN) is a prevalent condition in patients with metabolic syndrome (MetS). However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN) remain unclear.

In the current study, high-fat-fed mice (HF mice) were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF) mice.

Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 weeks of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin.

To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, and interleukin (IL)-6, IL1B as well as reduced anti-inflammatory IL-10 in in lumbar dorsal root ganglia (LDRG) of HF mice.



Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

My Take:
I know this one is a little technical. Remember, PubMed and all the news outlets have changed their format and no longer publish news articles on research. It’s just tips on washing your hands to avoid the flu and other trivia that panders to the simple minded.

Metabolic syndrome is the cornerstone of my practice. Each and every patient is evaluated for signs of MetS. In the lab, we look at the A1c for insulin resistance, the TSH for hypothyroidism, the serum lipids, and eGFR.

On physical exam, every visit, I first establish that the nervous system is responding appropriately. Then we look at inflammation. Approximately 40% of patients will exhibit cytokine inflammation.

Rather than administer intraperitoneal IL-10, I use ginger or Boswellia to reduce inflammatory cytokines. Ginger is effective in about 80% of cases. The remainder get Boswellia unless they have some form of autoimmune disease.

Hashimoto’s thyroiditis, RA, MS and other autoimmune diseases typically do not respond to these herbs. Recent research has indicated that vitamin D and methylcobalamin (bio-available B12) can be very effective in reducing inflammation in these patients. I have been combining the vitamin D and vitamin B12 with an herbal combination for viral and/or bacterial infection with excellent early results.

The Bottom Line:
Metabolic syndrome and its consequences – diabetes, heart disease and early mortality must be monitored and treated early. If you have any aspects of this syndrome seek qualified nutritional advice. If you already have PN then you are late to the dance and in real trouble, don’t delay any longer.

Source: PubMed February 6, 2018