Blocking inflammatory chemicals

This is part II of our noting of anticancer steps that should have benefit for nerve injury pain. The work is preliminary at this point, not in human trials for pain.


We have already written on the role of nitric oxice in the cascade of pain chemicals. It now appears that inducible nitric oxide is also linked to prostaglandin E2, another of the inflammtory eicosanoids (See using SEARCH at this site).

Since this traceable connection occurs in conjunction with ERK1.2, another of the pain chemicals, drugs used in cancer to block inducible Nitric Oxide Species (iNOS), which include NOS blocking RNA and also

Squamous cell cancer is the feared type of skin cancer. It also occurs in other organs. In this months, FASEB, Donnini et al have shown that “onsistently, iNOS-GC pathway inhibitors blocked mitogen-activated protein kinase-ERK1/2 phosphorylation, which was required to mediate PGE2 functions.” The cancer people are more than intrigued because it has also recently been discovered that “the levels of nitric oxide (NO) derived from inducible NO synthase (iNOS) and prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2) originated from tumor cells or tumor-associated inflammatory cells have been reported to correlate with tumor growth, metastasis, and angiogenesis.”

Most importantly, Donnini et al discovered that “iNOS-GC pathway inhibitors blocked mitogen-activated protein kinase-ERK1/2 phosphorylation, which was required to mediate PGE2 functions” In other words, nitric oxide is inflammatory and inflammation probably turns cells cancerous due to the growth positive effects of some of the chemicals we also find in neuroinflammation. There are pharmacologic inhibitors of iNOS/guanylate cyclase (GC). Either these or the anti NOS RNA may have a role in interrupting the pain cascade. MAPK and ERK were blocked by inhibition of iNOS-guanylate cyclase blocking. Time will tell if this will help stop neuroinflammation, and hence, nerve injury pain.

This is very much like our suggestion that NF Kappa B, which is activated by a Toll receptor, which is controlled by caspase-1, could be blocked by blocking Caspase-1. (See our review of Miggins article in Proc Natl Acad Sci U S A