Rationale for adjunctive precision jaw orthopedic therapy for the treatment of cancer

It is well established in medical literature that substance P (SP) plays an important role in numerous aspects of cancer (tumor cell proliferation, migration, invasion, infiltration and metastasis, and angiogenesis) [1–5] and is a valuable target in many types of cancer [1]. What is not well known is that elevated systemic SP levels are often caused by elevated tonicity within the trigeminal nerve from a misaligned jaw [6].

Background

Substance P is an 11-amino acid neuropeptide discovered in 1931. It has been widely studied since 1980. SP is released from the terminals of specific sensory nerves (primarily C fibers). It acts as a neurotransmitter and neuromodulator. Its receptor (NK-1) is widely distributed across many types of cytoplasmic membranes (neurons, glia, endothelia of capillaries and lymphatics, fibroblasts, stem cells, and white blood cells) in many tissues and organs. SP amplifies or excites most cellular processes and, hence, is a major neurosecretory modulator. This is done because SP attachment to its receptor causes membrane porosity, prolonged calcium influx, and hence, depolarization. This is the basis of much hypersensitivity (allergies, asthma, autoimmune disorders, etc.). It is a known major modulator of immunity and stimulation of cytokine production. SP has been associated with the regulation of mood disorders, anxiety, stress, neurogenesis, stem cell differentiation, nausea, respiratory rhythm, neurotoxicity, pain, seizures, heart disease, and nociception [7].

The trigeminal nerve becomes hyperactive with any trigeminal disturbance: airway obstruction, infected tooth, galvanic interactions, but far more often with craniomandibular dysfunction. Humans are all born these days with compromised craniomandibular structure (multiple generations consuming soft and nutritional-deficient diets is a primary suspect [8]), and hence, most people have a hidden burden of functional stress to a varying degree. The trigeminal nerve has 100 times more dense C fibers than any other nerve (that is why sensory homunculus is disproportionally devoted to the trigeminal area of innervation), and C fibers, when chronically stimulated can be a major source of SP [9].

There are multiple other means by which the trigeminal nerve can uniquely impact SP levels. Research has shown that irritation of the masseter muscle (controlled by the trigeminal nerve) leads to a spreading cascade of elevated substance P that progresses sequentially to the trigeminal ganglion and brain (causing glial activation), with eventual involvement of the spinal cord [10]. Chronic stimulation of the trigeminal nerve is known to cause windup and central sensitization [11]. Also, the trigeminal nerve, through various modulating pathways (trigeminal spinal thalamic track, impact on reticular tonicity, etc.), has the ability to excite spinal input, thus increasing C fiber response (hence, elevated SP levels).

Craniomandibular dysfunction and the accompanied neurological load can lead to a continuum of illnesses throughout one’s lifetime, inducing high medical utilization rates [12]. Craniomandibular stress causes a large number of neurological and inflammatory illnesses through multiple pathways, including elevation of SP levels (headaches, IBS, asthma, eczema, seizures, etc.) [13]. Therefore, it has the potential to also induce cancer, known to be associated with chronic inflammation. Perhaps elevated SP is the means by which tooth loss and periodontal disease increase risk of cancer [14].

I propose that precision jaw orthopedic therapy would be an immensely valuable adjunct in integrated cancer treatment by way of its ability to lower SP levels. This belief is based on a positive outcome in a number of cancer cases I have co-treated, and 40+ years’ experience in jaw orthopedics, which has proven highly effective in many other elevated SP diseases.

Even though elevated substance P levels are known to exacerbate cancer, most current cancer therapy, e.g. chemotherapy and radiation, raises substance P levels. Jaw orthopedic therapy would lower substance P levels, thus likely being even more effective than substance P antagonists, which are currently being tested [15,16]. Assuming that the patient had jaw dysfunction, jaw therapy would likely also act as a preventative measure and lower propensity to have recurrent cancer. Covert and overt jaw dysfunction is almost always overlooked when considering the causation and prevention of cancer.

Jaw orthopedic assessment is not something most dentists are taught how to do in dental school. Orthodontists are very good at straightening teeth but often leave jaws misaligned. Dentists often confuse the two concepts. Screening for jaw misalignment is very simple: one needs to open and close on a fair arc, bite, and talk on the same trajectory (no thrust right, left, or forward), and all teeth need to meet in a precise cusp/fossa contact with even force distribution. Precise assessment tools are available with bite force sensors, surface EMG, and kinesiographic scans.

Orthopedic jaw therapy is a multiple phase therapy. The first phase involves the use of removable dental appliances, which re-posture the lower jaw in an ideal functional position (on a relaxed trajectory), with even contact on posterior molars (pivoting mechanics). The second phase is to stabilize the lower jaw in the ideal position with either crowns and/or orthodontics. Phase III is retention, with typically, a night-time appliance only.

Hence, I believe that investigation into this area needs to be done in great haste.