PERIPHERAL NEUROPATHY
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Patient Summary:
- Peripheral neuropathy is a diagnosis made when patients demonstrate a malfunction of nerve fibers connecting the central nervous system (the brain and spinal cord) and the rest of the body.
- This may involve just one particular nerve or it may involve many nerve fibers at the same time.
- When only one nerve fiber section is involved, the patient may experience numbness or pain, in one area of their body.
- Many times when there are multiple nerves involved, the area of numbness or pain will appear as a "stocking" or "glove" distribution.
- Peripheral neuropathies may be inherited, caused by other diseases such as diabetes, or may be the result of injury.
- No matter what the cause, the end result is that the peripheral nerve no longer is able to conduct its messages in a normal manner.
- Research has shown that this is due to a lack of adequate oxygen being supplied to the nerve. It has been demonstrated in the laboratory that peripheral neuropathies can be reversed, by supplying adequate oxygen to the nerves.
- In a recent study performed in conjunction with our office, it was shown that not only did the patients feel better but also that the peripheral neuropathies could be improved with our treatments. 59% of the patients who received one hour of treatment per day had nerve conduction improvement by the end of one month.
Physician Summary:
- Clinical experience has shown that STS treatments are extremely effective in decreasing the morbidity of Peripheral Neuropathies.
- This is probably due to an increase of endoneural circulation caused by the creation of VIP (Vasoactive Intestinal Polypeptide), CGRP (Calcitonin Gene-related Peptide), and the electrical stimulation itself.
- The production of cAMP (cyclic adenosine monophosphate).
- Multiple digital skin temperature, skin temperature gradients, and photoplethysmography all show that STS treatments increase peripheral perfusion.
- In addition, it has been shown that plasma VIP levels are increased and that heart rate variability decreases, with STS treatments.
- Below, there is a study of STS treatments for peripheral neuropathy patients. 59% of the patients who received one hour of treatment per day had nerve conduction improvement by the end of one month. This included two patients who had not had F waves in tested nerves, for over 10 years. Following 30 days of treatment, F waves were detected in these patients.
Effects of Sympathetic Therapy on Chronic Pain and
Nerve Conduction Deficits in Peripheral Neuropathy Patients
Abstract. 20 patients suffering from chronic pain, primarily caused by peripheral neuropathies, received sympathetic therapy treatments (Dynatron STS, Dynatronics Corporation, Salt Lake City, Utah). Sympathetic therapy treats the sympathetic nervous system utilizing electric current. Patients, ranging in age from 37 to 75 years old, were treated daily for a period of 28 days. Pre and post nerve conduction velocity testing was performed on 18 of these patients. At the onset of the study, 75% of the patients reported moderate to severe pain. By day five, 50% reported moderate to severe pain. By day eighteen, only 14% of the patients reported moderate to severe pain. At the end of the 28 days, 80% of the patients reported an overall improvement in their quality of life, 80% of the patients reported that they were sleeping better, and 40% of the patients were able to significantly reduce their medications (Neurontin, Ultram, narcotics, etc.). In addition, a majority of the patients had varying degrees of nerve conduction normalization. These patients had previously been unresponsive to other therapeutic regimens.
INTRODUCTION
It is estimated that there are more than 20 million people in the United States who have been diagnosed as having peripheral neuropathies. In the past, physicians have not had an effective treatment for this disease process.
Recently, encouraging results have been seen in the treatment of patients with peripheral neuropathies utilizing the Dynatron STS. This system utilizes low frequency, high intensity transcutaneous sinusoidal waveform stimulation through extremely long sections of specific peripheral nerves, involving specific dermatomes and thermatomes; as well as, specific electrode placements. In addition, beat frequencies are chosen to maximize the production of various neuropeptides and neurotransmitters. This combination is formatted to have the stimulation involve the specific pad placement, peripheral nerve pathways, spinal anatomy, sympathetic nervous system anatomy, spinal nerve anatomy, as well as, the cellular and tissue physiology so as to benefit the effected areas of the body.
METHODOLOGY
The study was comprised of 20 patients. The patients had a nerve conduction evaluation before and after the 28 days of treatment. The patients were not allowed to miss more than 2 days in a row nor more than a total of 3 days throughout the 28 days of treatment. The patients were not allowed to have skin piercing procedures (injections or surgery) during the study. Due to a lack of communication between medical offices, two of the patients did not receive pretreatment nerve conduction studies. Therefore, the subjective summary is for 20 patients but the objective summary is only for 18 patients.
The patients completed a pain grid depicting the area of worst pain, as well as, secondary areas of pain. The pad placement protocols were chosen from the Dynatronic STS clinical software, on the basis of the location of the worst pain, that day. The patients received a total of one hour of treatment, per day. The treatment was divided into a 20 minute and 40 minute section. Treatment was given through the hands and the feet. If the patient's worst pain was above the waist, the 40-minute treatment was given through the hands and the 20-minute treatment was given through the feet. If the patient's worst pain was below the waist, the 40-minute treatment was given through the feet and the 20-minute treatment was given through the hands.
RESULTS
SUBJECTIVE (20 PATIENTS):
85% (17) reported at least 45% relief of all symptoms
10% (2) reported between 35 and 45% relief of all symptoms
5% (1) did not report pain relief but did report other improvements.
40% (8) were able to significantly reduce their medications (Neurontin, Ultram, and narcotics)
80% (16) reported an overall improvement in their quality of life
80% (16) reported better sleep
85% (17) stated that they wished to continue the daily treatments
OBJECTIVE (18 PATIENTS):
Overall, 59% (11) of the patients had improvement in their nerve conduction.
22% (4) had nerve conduction when there had been no conduction prior to the study
5% (1) had an "F" wave when none was apparent prior to the study
27% (5) had improvement in the "F" wave
27% (5) had CMAP amplitude improvement
27% (5) had Motor Conduction Velocity improvement
5% (1) had Motor Distal Latency improvement
DISCUSSION
It has been shown by numerous investigators, that a reduction or impaired blood flow and the resultant endoneurial hypoxia are important factors underlying nerve conduction deficits. Cameron showed that nerve blood flow in chronic experimental diabetes was reduced by 41% as early as 1 week after diabetes induction. However, with a chemical adrenergic sympathectomy, blood flow increased to within the normal range. Conduction velocity, depressed by 26% with diabetes, was normalized by treatment. (3)
Other authors report similar results. Terata found that in 4 week-streptozotocin-induced diabetic rats the sciatic motor nerve conduction velocity was decreased by 22% and the sciatic endoneural blood flow was decreased by 49%. (23)
Cameron also reported that chronic increases in nerve electrical activation promote mechanisms that reverse conduction deficits in diabetic rats. (4)
In another paper Cameron concluded that electrical stimulation causes activity-related improvements in diabetic nerve blood flow and metabolism. He felt that the data demonstrated that chronic electrical activation of one sciatic nerve branch can, over several days, produce profound changes in conduction velocity that also affects axons not directly stimulated but that share the same sciatic vasa nervorum blood supply and microenvironment. Sciatic endoneurial blood flow is reduced by diabetes and the consequent endoneurial hypoxia has been hypothesized to result in short-term changes because of reduced ATP production and long-term damage to axons and Schwann cells mediated by oxygen-free radicals. (5)
Winter postulated that there is an obvious decrease in electrical transmission along the nerves that are pathologically changed by demyelinization, which delays or completely interrupts nerve signals. The electrical deficit blocking the polarization and depolarization to take place can be normalized by the biphasic square wave supplied by TNS. (25)
Brain found that a subcutaneous injection of VIP induces a local erythema persisting for 3 hours. In contrast, CGRP induced an intense local erythema, slow in onset but very persistent, up to 10-12 hours duration at high doses. Brain found that in some patients with Raynaud's phenomenon or diabetic polyneuropathy, electrical transcutaneous nerve stimulation induces vasodilation and relief from ischemic pain. It has been suggested that the release of an endogenous vasodilator is partly responsible for the beneficial effects. Transcutaneous nerve stimulation has been associated with a rise in plasma VIP in these patients and normal individuals, although some studies have suggested that this endogenous vasodilator is not VIP but is probably CGRP. In the periphery, immunoreactive CGRP was found in thin beaded nerve fibers that were associated with the smooth muscle of blood vessels and was found to work on arterioles. (1)
Jager found that skin blood flow, assessed by a laser Doppler unit, was increased up to 682% of the basal level by CGRP. CGRP increased regional blood flow to the brain and the skin at the expense of the gastrointestinal tract. (9)
Kaada found that distant, low frequency TNS (2 Hz) improved microcirculation in ischemic limbs of patients with Raynaud's phenomenon and diabetic neuropathy and to accelerate healing of chronic skin ulcerations.
He also found that skin temperature increased 1.8 to 2.8 degrees centigrade and persisted for several hours after treatment. Plasma VIP was increased 60% following stimulation.
Kaada felt that the improved microcirculation of the skin was most likely caused by a sympatho-inhibition effectuated through a central serotoninergic link, since the response was blocked by the serotonin blocker cyproheptadine. In addition, the vasodilation was proportional to the increase in plasma VIP.
He stated that the mechanism of the relief of pain from wounds and ulcers was probably due to the vasodilation and endorphins, as well as, the release of ACTH and adrenocortical hormones caused by the TNS. Naloxone did not alter the vasodilatory effect or pain relief. He felt that this was due to an increase in VIP, which evidently affects the arterio-venous anastomoses. (12(13)(14)
Kaada felt that the primary cause of the improved microcirculation resulting from the electrical stimulation may be due to:
1. Sympatho-inhibition. It has been shown that this reflex inhibition is relayed over the depressor area of the medulla oblongata. Experiments have shown that the vasodilatory response can be antagonized by the administration of a central serotonin blocker, suggesting the involvement of a central serotonergic link.
2. Release of a vasodilatory substance, probably vasoactive intestinal polypeptide.
3. ACTH-release. In addition to improved microcirculation, tissue repair may possibly also be accelerated by an endogenous ACTH-release, which has been shown to occur in response to low-frequency peripheral nerve stimulation. (10)
VIP is not a blood-borne hormone. An increase in plasma VIP in the systemic circulation represents an overflow from synapses, caused either by an increased release or by a reduced degradation of the neuromodulator.
An unexpected finding in these studies was that the resting values of plasma VIP were significantly (about 30%) lower in Raynaud and sclerodermic patients than in normal subjects. It has previously been suggested that one explanation could be that this lower plasma VIP concentration represents a defect in the VIP system in these patients and that it is a pathogenetic factor in the disease. (11)
Said states that VIP stimulates the release of multiple chemicals, including serotonin. It has been shown that VIP enhances the binding of serotonin to its receptors in rat hippocampus. VIP binding sites have been identified in the hypothalamus, cerebral cortex, and pineal. Intracerebroventricular administration of VIP has a hypnogenic effect in rats and cats rendered partially insomniac. VIP stimulates cyclic AMP production, which in turn increases the production of melatonin. VIP is a dominant factor in increasing the availability of glucose from glycogen, promotes glucose utilization, and inhibits platelet aggregation. (6)(20)
The concentration of VIP in CSF from diabetic patients was significantly decreased, compared with that from the controls. (24)
It has been found that diabetic patients without clinical or neurophysiological evidence of polyneuropathy had reduced density of CGRP fibers when compared to controls. (17)
It was found that CGRP retains biological activity for long periods in cutaneous tissue fluid. However, even extremely small amounts of substance P converts the long-lasting vasodilation induced by CGRP into a transient response. It was found that substance P causes a release of proteolytic enzymes from mast cells, which cause the destruction of CGRP. (2)
It has been found that CGRP induces a rapid and dose-dependent accumulation of intracellular cyclic AMP (cAMP). CGRP synthesis is increased after nerve injury, suggesting that this peptide may play a role in nerve regeneration. CGRP promotes Schwann cell proliferation through an activation of certain c-AMP pathways. (19)
There was a significant increase in intracellular cAMP with low-frequency (10 Hz) currents. (16)(22)
It was found that VIP caused increased intracellular cAMP. (18)
Yamamoto showed that there is a c-AMP-dependent differential regulation of Schwann cell extracellular matrix gene expression, which may be related to the role of each ECM molecule in the peripheral nerve development and regeneration. (26)
It was found that the cyclic AMP (cAMP) content in the sciatic nerves of diabetic rats was significantly lower than in those of normal rats. Administration of dibutyryl cyclic AMP significantly restored the cAMP content in the sciatic nerves and motor nerve conduction velocity, which reflects nerve function. It was concluded that reduction of cAMP content in peripheral nerves may be involved in the pathogenesis of diabetic neuropathy and is mainly caused by the impairment of adenylate cyclase activity in the diabetic state. (21)
Existing data indicates that F-wave studies are the most sensitive measure of nerve pathology, with the least day-to-day variability. (7)(8)(15)
CONCLUSIONS
In reviewing this study's results, it could be hypothesized that improved circulation to the nerves resulted in the improvement in the peripheral neuropathy patients. The current working hypothesis for this study is that the STS treatments are effective due to a combination of the following aspects of the treatments: low frequency electrical current passing through long sections of nerves, production of cyclic adenosine monophosphate, electrode pad placement (including acupuncture points), the choice of the peripheral nerves being stimulated so that there is a cross-over effect in the CNS, leakage of action potentials from the nerves being stimulated into nerves entering the sympathetic ganglia, the quadrilateral location of stimulation, creation of action potentials through sympathetic nerves in the peripheral nerves being stimulated, production of ACTH, production of dynorphins, enkephalins or beta-endorphins, creation of action potentials through sympathetic nerves in the peripheral nerves being stimulated which enter the sympathetic ganglia directly, local analgesia resulting in a decrease of substance P; and/or the production of circulation altering neuropeptides such as vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP).
The patients in this study were able to improve subjectively in spite of a reduction of medications. In addition, this study showed that the Dynatron STS System was able to improve the nerve conduction in a significant portion of the patients. Most impressive of the follow up testing was that 32% of the patients tested had improvement in the F-wave studies.
Nerve Conduction Deficits in Peripheral Neuropathy Patients
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