Novel Molecular Factors in the Pathochemical Mechanisms Supporting Chronic Back Pain?




Igor G.Bondarenko, MD, PhD; Juhani Tevren, DC; Rainer Boeger, MD, Prof.; Jukka Chydenius,DC


Recurrent character of the chronic back pain often indicates that there are endogenous chemical mechanisms sustaining the local aseptic (non-microbial) inflammation in the connective tissue and, therefore, pain. The mechanism that has been described best is an overproduction of the mediators of inflammation in the tissues such as prostaglandins and leukotrienes. Pharmacological approach to the correction of that pathophysiological process is the use of non-steroidal anti-inflammatory drugs (“pain-killers”) supposed to inhibit cyclooxygenase and lipoxygenase, the enzymes catalysing the synthesis of the aforementioned pro-inflammatory chemicals.
There exists a different cohort of endogenous substances in the body which, although not behaving as direct inducers of the pain by acting on the nociceptors in the damaged area, may impair the structural integrity of the major proteins of connective tissue – collagen(s) and elastin. Homocysteine, a sulfur-containing amino acid, has been equivocally claimed to be associated with the higher risk of cardiovascular conditions. Hyperhomocysteinemia has been proven to be an independent risk factor of cardiovascular disease, including atherosclerosis and stroke, and is connected to insulin resistance. There is also a link between elevated levels of homocysteine and neurodegenerative diseases. Evidence exists that homocysteine-induced damage to the vascular wall is due to the impairment in the structure of its collagen and elastin, both by the inhibition of the assembly/maturation of those proteins.
Destructive effects of homocysteine are not restricted by vascular wall only. Hyperhomocysteinemia has been shown to be associated with the increased risk of hip fracture in the elderly. As early as in 1976, experiments by Griffiths et al. demonstrated that excess homocysteine can decrease the level of cross-linking of the collagen in the tendons, thus making collagen mechanically weaker. Twenty years later, Liu G. et al. (1997) confirmed the irreversible inhibition of lysyl oxidase, the enzyme responsible for strengthening collagen and elastin by cross-linking their filamentous chains, by homocysteine thiolactone – the product of homocysteine breakdown in the body. A single-point mutation in the gene leading to the elevation of homocysteine has been proven to be associated even with the decrease of bone mineral density.
Another endogenous chemical potentially involved in the labilisation of the major proteins of connective tissue is NG, NG-asymmetrical dimethylarginine (ADMA). This methylated derivative of the amino acid arginine, described by P. Vallance et al. (1992), is synthesised in the body from it own proteins and acts as a specific inhibitor of nitric oxide synthase family, therefore diminishing the production of nitric oxide in the tissues. Similar to homocysteine, elevation of ADMA level is associated with the increased risk of cardiovascular conditions – it has been reported in hypercholesterolaemia, peripheral arterial occlusive disease, hypertension, chronic heart failure, and coronary artery disease, as well as in diabetes mellitus. Moreover, higher values of ADMA in blood have been diagnosed in patients with hyperhomocysteinemia, which emphasises the pathophysiological proximity and interrelations between homocysteine and ADMA in the pathogenesis of cardiovascular diseases.
Again, as in the case of homocysteine, it seemed plausible to suggest that the effects of ADMA on blood vessel wall could be, in particular, accounted for by its damaging action on the connective tissue proteins. In that case, the association between the elevation of ADMA and the possible impairment of collagen and/or elastin could result to other clinical conditions, in which structural integrity of collagen/elastin plays a primary role. Very few disperse data indirectly support the suggestion. Experimental studies by Lu R. et al. (2002) have demonstrated that age-related decrease in bone mineral density in the spine, tibias and femora correlated with the increase of serum levels of ADMA. In particular, it could be accounted for by the inhibition of osteoblastic differentiation by ADMA. In clinical studies, almost two-fold elevation of ADMA levels in the cerebrospinal fluid of the patients with lumbar spinal canal stenosis has been demonstrated.

In our preliminary study, levels of ADMA (analysed by high-performance liquid chromatography) in the blood serum of 10 patients (male: 8, female: 2, age: 31-69) with chronic back pain were found to be close to the upper reference limit (“upper normal value”) or to exceed it.

If the hypothesis on the role of endogenous destabilisers of major connective tissue proteins in the mechanisms of chronic pain is supported in further studies, a specific nutritional supplementation can be developed to reduce the levels of ADMA and/or homocysteine in the body fluids and, therefore, to augment the efficiency of chiropractic treatment of chronic back pain.



The use of complementary medical techniques for the optimisation of treatment of patients with circumoral herpes simplex

Igor G. Bondarenko, MD, PhD, Jukka Chydenius, DC
CHYDENIUS Clinic, Helsinki, Finland

Applied kinesiology is a modern neurophysiology-based area of complementary medicine that, through the use of a standard muscle test (SMT), enables a practitioner to select a treatment (pharmaceutical, nutritional, homoeopathic etc.) specific for each patient (both substances and their doses).
28 patients (both genders, 20-57 years) with clinically diagnosed circumoral herpes simplex (CHS) were enrolled in the study. With the SMT, we prospectively evaluated the applicability of two classes of natural products to the treatment of CHS: a) cofactors and allosteric acivators (minerals, coenzymes) of myeloperoxidase, the major antimicrobial enzyme of neutrophils and macrophages; b) inhibitors of the enzymes catabolising nucleotides, which, due to feedback mechanism, were expected to inhibit viral replication. Individual combinations of the products and required dosages were selected for each patient with the use of the SMT.
Major symptoms of CHS (tingling, itching, burning, tenderness, prickling, soreness, bump/swelling, small blisters, oozing blisters) were daily monitored on a 10-point scale. Days 1, 3 and 7 were arbitrarily set as fixed time markers. The aforementioned nutritional supplementation produced a clinical cure (all CHS symptoms score of zero) in 2 patients (7%) on the day 1, in 10 patients (36%) on the day 3, in 25 patients (89%) – on the day 7. All lesions were cured on the day 10. Score data showed a significant improvement on the day 7 compared to baseline and day 3. Biochemical mechanisms of action of every particular supplement used and the possible role of applied kinesiology in the treatment of CHS are discussed.

Corresponding author: Igor G. Bondarenko
CHYDENIUS Clinic, Yrjönkatu 21 C, 00100 Helsinki, Finland




TARGETED METABOLIC STIMULATION OF THE HOST RESISTANCE IN MEBENDAZOLE-TOLERANT NEMATODOSES
Igor G Bondarenko*,, Jukka Chydenius, Erkin I Musabayev, Juhani Tevren
CHYDENIUS Clinic, Yrjönkatu 21 C, 00100 Helsinki, Finland
Institute of Virology, Muradova St. 7, 700133 Tashkent, Uzbekistan

Background: Even in regions highly endemic in ascariasis and trichiuriasis, broad use of mebendazole and related anti-nematode therapy has been proven to be insufficient, with the second wave of the prevalence of those nematodoses raising to 45-55% of the initial values (Bundy DA et al.,1987; Haswell-Elkins M, Anderson RM, 1988). We have assessed the efficacy of an alternate approach to the treatment of the nematodoses aimed at the substrate induction of nitric oxide synthases in the host tissues in order to stimulate controlled production of peroxynitrite, a natural endogenous anti-parasitic compound.

Study design: Case study.

Study group: Patients (male: 36, female: 44) with ascariasis and trichiuriasis manifesting appropriate signs and symptoms within 3-6 months after the treatment with mebendazole (Vermox, Wormin) in accordance with manufacturer’s instructions.

Methods: Oral administration of arginine and mineral cofactors of nitric oxide synthases for three weeks.

Results: Significant clinical improvement and negative faecal microscopy registered on four consecutive days after finishing the supplementation have been observed in 29 male and 38 female patients. Non-responders were additionally supplemented with the substrates/cofactors stimulating the production of nitric oxide/peroxynitrite in a related enzymatic pathway (activating specific intestinal oxidoreductases), after which they all manifested clinical improvement accompanied by negative faecal microscopy.

Biochemical mechanisms of the beneficial effects of the aforementioned metabolic stimulation, as well as its indications, contra-indications and possible side effects are being discussed.