Chronic pain, even when attributed to an identifiable cause, is an expression of a body in trouble. Persistent pain is almost always accompanied by elevated expression of NF-kappaB and associated inflammatory genes. Oxidative stress initiates the process of freeing NK-kappaB from its cytosolic anchor, IkappaB. Once freed, it enters the nucleus, binds to DNA and triggers the activation of pro-inflammatory genes. NF-kappaB is rightfully considered to be the gateway to inflammation as its activation clicks into place the viscous pathway of: inflammation àtissue destruction à pain. Remembering this underlying pathway puts the diagnostic work-up of pain in a very critical light. The most important question becomes, what is causing recurrent oxidative stress? The answer to this question is the most impactful treatment target. While it is certainly important to utilize therapies that address other aspects of this process such as the down-regulation of NF-kappaB [there are many interventions for this, including botanical flavonoids, essential fatty acids, and even stress (down-regulates cortisol, an initiator of NF-kappaB)] as well as the modification of inflammatory gene expression (methylating agents such as folic acid, pyridoxine and botanical flavonoids), ultimate success lies in removing the original oxidative insult. Sometimes, this is removal process is relatively straightforward, as in the case of an injury or infection. However, in most cases, this quest is challenging and complex.
Chronic oxidative insult can be the result of overlapping factors, some of which are long-standing and others are more recent, but which cumulatively trip the NF-kappB trigger. Oxidation can occur as the result of the normal acts of daily living (eating, breathing, moving) which, in an antioxidant-deficient body, may be enough to begin an oxidative inflammatory assault. Additionally, certain physiological states increase oxidative stress, namely obesity and insulin resistance. Environmental exposures with resultant tissue burden of toxicants leads to oxidative stress. Emotional stress increases oxidation. Chronic sleep deprivation increases oxidation. The list of oxidation triggers goes on to include hormonal factors, dietary deficiencies, genetic polymorphisms, and other long-standing diseases.
While this all may seem tangential to the central issue of chronic pain, it is anything but. Chronic pain is mediated by NF-kappaB induced inflammation. NF-kappaB is triggered by oxidative stress. Identifying and remediating the underlying sources of oxidation will provide the most effective long-term pain management plan. While this process can be laborious, and depending upon the approach used, costly to the patient, the end-result is almost always well worth the effort.