Blog #9 - Chondroitin Sulfate Shines

A little history...

Discat plus is a Chondroitin Sulfate formula I developed in 1966 following reading the work of Cole, Ghosh and Taylor in a two volume text entitled “THE BIOLOGY OF THE INTERVERTEBRAL DISC”. This two volume text was far ahead of its time. Following studying it, I gained awareness of stopping disc degeneration, prompting disc regeneration, and a beginning of possibly controlling spine pain with chondroitin sulfate administration to people.

The source of Chondroitin Sulfate I used and still use was perna canaliculus, a green lipped mussel from New Zealand and Australia that is harvested from the ocean. It is the most potent source of Chondroitin Sulfate known. (welburn) The intervertebral disc contains a mucopolysaccharide compound know as glycosaminoglycan that absorbs fluid to give the disc its property of turgor (stiffness) within its cells. Loss of glycosaminoglycan accompanies disc degeneration and disc herniation. Glycosaminoglycan is Chondroitin Sulfate. Thus the relationship between administering Chondroitin Sulfate (Discat Plus) along with Cox® Technic for treating disc degeneration and herniation began.

In 1966 I formulated Discat Plus (with Chondroitin Sulfate). This was twenty to thirty years before commercial ventures like health food stores and commercial television learned of it and started to sell it.  Remember it takes 17 years for a new idea or fact to settle into common knowledge. This was true for chondroitin sulfate.

and today... 

Now we are seeing pain relief as well as the anti-inflammatory benefits of Chondroitin Sulfate (as in Discat Plus). Please read the following relief of tactile allodynia in the mouse model when oral chondroitin sulfate was given. 

Source: Nemoto W, Yamada K, Ogata Y, Nakagawasai O, Onodera K, Sakurai H, Tan-No K. Chondroitin sulfate attenuates formalin-induced persistent tactile allodynia. J Pharmacol Sci Aug 5. pii: S1347-8613(16)30091-3. doi: 10.1016/j.jphs.2016.07.009. [Epub ahead of print]

We examined the effect of chondroitin sulfate (CS), a compound used in the treatment of osteoarthritis and joint pain, on the formalin-induced tactile allodynia in mice. A repeated oral administration of CS (300 mg/kg, b.i.d.) significantly ameliorated the formalin-induced tactile allodynia from day 10 after formalin injection. On day 14, the phosphorylation of spinal p38 MAPK and subsequent increase in c-Fos-immunoreactive dorsal lumbar neurons were attenuated by the repeated administration of CS. These findings suggest that CS attenuates formalin-induced tactile allodynia through the inhibition of p38 MAPK phosphorylation and subsequent up-regulation of c-Fos expression in the dorsal lumbar spinal cord.

CHONDROITIN SULFATE (CS) IS USED IN THE TREATMENT OF OSTEOARTHRITIS AND JOINT PAIN. IT HAS ALSO SHOWN RELIEF OF TACTILE ALLODYNIA IN MOUSE STUDIES. A REPEATED ORAL ADMINISTRATION OF CS (300 MG/KG, B.I.D.) SIGNIFICANTLY AMELIORATED THE FORMALIN-INDUCED TACTILE ALLODYNIA FROM DAY 10 AFTER FORMALIN INJECTION. ON DAY 14, THE PHOSPHORYLATION OF SPINAL P38 MAPK AND SUBSEQUENT INCREASE IN C-FOS-IMMUNOREACTIVE DORSAL LUMBAR NEURONS WERE ATTENUATED BY THE REPEATED ADMINISTRATION OF CS. THESE FINDINGS SUGGEST THAT CS ATTENUATES FORMALIN-INDUCED TACTILE ALLODYNIA THROUGH THE INHIBITION OF P38 MAPK PHOSPHORYLATION AND SUBSEQUENT UP-REGULATION OF C-FOS EXPRESSION IN THE DORSAL LUMBAR SPINAL CORD.

First, what is tactile allodynia? It is pain caused by touch such as clothing against the skin. It is pain caused by so little irritation it would not be considered to cause pain.

Second, what does phosphorylation of spinal p38 mapk and subsequent increase in c-fos-immunoreactive dorsal lumbar neurons mean?

Let's first review. What are MAPK, ERK, P38 pathways? Cellular responses to many external stimuli involve the activation of several types of MAPK (Mitogen-Activated Protein Kinase) signaling pathways. MAPKs are a family of serine/threonine kinases that comprise 3 major subgroups, namely, ERK (Extracellular signal–Regulated Kinase), p38 MAPK and JNK (c-Jun N-terminal Kinases).

An understanding of kinases is basic. Genetic and protein information on pain and disease involves knowing that protein tyrosine kinase is an enzyme that transfers po4 from ATP to protein in the cell. The released po4 attaches to tyrosine to form tyrosine phosphate which then attaches to serine and threonine and this regulates cell division. If irregular, it will set abnormal cell division – cancer.

Pathways to transmit proteins through the cell wall from receptor to DNA, RNA of nucleus of the cell.  MAPK–ERK pathway conducts the protein such as tyrosine kinase attached to serine and threonine through the cell wall into the nucleus of the cell. The p38 pathway routes chemicals through the cell wall into the nucleus of the cell. In this paper, chondroitin sulfate is found to inhibit the p38 pathway to relieve tactile allodynia.

This represents another potential benefit of chondroitin sulfate as an anti-inflammatory pain control.

For further information, I am also sharing the following paper on attenuating the MAPK p38 pathway for neuropathy pain relief (Chen et al). Please know I am not expert in such deep subject cellular pathways, but this is basic knowledge for your consideration. - JMC

Source: Chen NF, Chen WF, Sung CS, Lu CH, Chen CL, Hung HC, Feng CW, Chen CH, Tsui KH , Kuo HM, Wang HD, Wen ZH, Huang SY. Contributions of p38 and ERK to the antinociceptive effects of TGF-β1 in chronic constriction injury-induced neuropathic rats. J Headache Pain. 2016 Dec;17(1):72. Epub 2016 Aug 19.

HERE IS AN EXAMPLE OF SUPPRESSION OF MAPK, ERK, P38 ARE ANTINOCICEPTIVE FOR CHRONIC CONSTRICTION OF A NERVE BY TRANFORMING GROWTH FACTOR-B. TGF-Β1-INDUCED ANALGESIA DURING NEUROPATHY. Transforming growth factor-βs (TGF-βs) are a group of multifunctional proteins that have neuroprotective roles in various experimental models. intrathecal (i.t.) injections of TGF-β1 significantly inhibit neuropathy-induced thermal hyperalgesia, spinal microglia and astrocyte activation, as well as upregulation of tumor necrosis factor-α.  During persistent pain, activation of MAPKs, especially p38 and extracellular signal-regulated kinase (ERK), have crucial roles in the induction and maintenance of pain hypersensitivity. TGF-β1 markedly inhibited phospho-p38 upregulation in neurons, microglial cells, and astrocytes. However, i.t. injection of TGF-β1 also reduced phospho-ERK upregulation in microglial cells and astrocytes.

CONCLUSIONS: The present results demonstrate that suppressing p38 and ERK activity affects TGF-β1-induced analgesia during neuropathy.

Researchers from Australia's RMIT University and SGE International Pty Ltd state that novel omega-3 polyunsaturated fatty acids extracts from the green-lipped mussel (Perna canaliculus) inhibited leukotriene and cyclo-oxygenase (COX) activity, both of which are involved in the inflammatory process. Chronic inflammation has been linked to a range of conditions like heart disease, osteoporosis, cognitive decline and Alzheimer's, and type-2 diabetes. (http://www.nutraingredients-usa.com/Research/Studies-support-green-lipped-mussel-s-anti-inflammatory-properties)

The functions of CHONDROITIN SULFATE PROTEOGLYCANS (CS-PGs) in the central nervous system can be categorized as the regulation of cell adhesion and migration, neurite formation, polarization of neurons, synaptic plasticity, survival of neurons, etc. Chondroitin sulfate (perna canaliculus) is reported to:

• Repair degraded bone

• Increase absorption and replacement of calcium

• Rebuild damaged bone, cartilage, tendon, ligament, and disc

Again, I first formulated Discat Plus in 1966, continued its improvement as research dictated, and continue to use it and make it available to doctors who understand its benefits. Also its use is strengthened by continued research. If interested in this beneficial nutritional addition to the treatment of disc degeneration and spinal stenosis, contact us at www.coxtrc.com and more specifically http://coxtrc.com/supplements/discatplus.html. Thank you!