BACK PAIN
Patient Summary:
Many patients suffer from back pain of short or long duration. Many of these patients have had an injury at work. Prior to STS treatments, there have been no good methods of treating this ailment and many back injuries have become chronic pain disorders, which prevent the patient from gainful employment or even being able to perform normal tasks of life. In our clinic, we have had excellent results utilizing STS treatments to stop back pain of short or long duration. STS treatments are designed to create various neuropeptides (normally occurring substances within the body), which prevent the underlying disease processes. Therefore, the STS treatments are designed to stop the cause of the back pain not just to hide the pain.
Physician Summary:
Medical literature has shown the beneficial effects of the vasodilatory action of VIP (Vasoactive Intestinal Polypeptide) and CGRP (Calcitonin Gene-related Peptide) in preventing and treating the etiology of acute and chronic back pain. This literature also shows that surgery and other forms of treatment have not been found to be efficacious. STS treatments are designed to create VIP (Vasoactive Intestinal Polypeptide) and CGRP (Calcitonin Gene-related Peptide). It has been shown that CGRP and VIP are essential for normal bone continuity, production, and circulation. CGRP and VIP have been found to decrease osteoclastic activity and increase osteoblastic activity. Our clinical experience has shown that STS treatments are an extremely effective treatment for acute and chronic back pain.
MEDICAL JOURNAL BACKGROUND INFORMATION
In a recent study performed by Ernesto Guido, M.D.; it was found that treatment utilizing the Dynatronic STS system successfully decreased the objective signs and subjective symptoms of peripheral neuropathy patients. During that study, all three of the patients who also exhibited significant chronic low back pain stated that their back pain was markedly improved, with the treatments. (25) One patient, in the peripheral neuropathy study had such overwhelming back pain that Dr. Guido expressed concern that she would not be able to complete the 28 day study. She was reduced to tears, when attempting to walk, even with the aid of a walker. In addition, the patient had diabetes, which was only somewhat under control, with oral medicine. During the study, the patient was able to discontinue all pain medications and NSAIDs. Following the study, the patient, the patient was able to walk, with no tears but still utilizing the walker. The patient continued STS treatments at home utilizing a home unit and, 18 months after beginning these treatments, the patient discontinued the use of her walker and was able to walk, without pain. With the continuing treatments and the increased activity, the patient's blood glucose stabilized between 80 and 110 mg and the patient's family physician discontinued her oral diabetic medication. Even without this medication, the patient's blood glucose has remained, within normal limits.
In reviewing that study's results, it could be hypothesized that improved circulation to the nerves resulted in the improvement in the peripheral neuropathy patients. If this is true, then it could be hypothesized that the decrease in the patients' back symptoms was due to an improved microcirculation and bone proliferation caused by the creation of various neuropeptides by the treatment.
The current working hypothesis 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, and/or the production of circulation altering neuropeptides (such as vasoactive intestinal polypeptide and calcitonin gene-related peptide). It has been shown that CGRP and VIP are essential for normal bone continuity, production, and circulation.
Approximately 70% of adults suffer from low back pain at some time. Low back pain is second to upper respiratory problems as a symptom-related reason for visits to a physician. (1)(27)
It has been found that low back pain is the most common cause of work-related disability in people under the age of 45 and is the most expensive cause of work-related disability, in terms of worker's compensation and medical expenses. (1)
Chronic low back pain may be associated with the failure of previous treatment or depression. (1)(2)(13)(11)
A number of physicians feel that complete relief of low back pain symptoms may be unrealistic, and therapeutic goals may need to be refocused on optimizing daily function. It has been shown that multiple surgical procedures are rarely helpful. (16)
There is no evidence from clinical trials or cohort studies that surgery is effective for patients who have low back pain unless they have sciatica, pseudoclaudication, or spondylolisthesis. (24)
In a study performed by Linsinski, it was found that dysfunction of the erector spinae muscle plays a significant role in chronic low back pain. He also found that surface EMG is an objective, non-invasive method of examining function of the erector spinae muscle. (47)
There is increasing evidence that ischemia plays an important role in the clinical syndromes associated with nerve root compression. The dorsal root ganglia (DRG) do not have the diffusion barrier that is found in peripheral nerves and the permeability of the microvessels is higher than that noted in nerve roots which, in turn, is higher than that in peripheral nerves. This results in a much greater response in the DRG to compression with the formation of edema that, in turn, makes the DRG sensitive to mechanical stimuli. Mechanical irritation has been shown to generated spontaneous ectopic discharges in the DRG that can last several minutes with repetitive firing of axons of all sizes. (26)(12)
Low calcitonin gene-related peptide levels have been demonstrated in cerebrospinal fluid from chronic back pain patients. (46)
It has been found that CGRP has an osteogenic stimulating effect by increasing the number and size of bone colonies in vitro. (3)
Recent evidence suggests that sensory nerve fibers of the dental pulp secrete calcitonin gene related peptide exactly where secondary or tertiary dentin is mineralized. In addition, calcitonin gene related peptide raises the level of cyclic adenosine monophosphate in osteoblasts, indicating a potential effect on secretory activity in bone. Calcitonin gene related peptide has an osteogenic stimulating effect, either by stimulating stem cell mitosis or osteoprogenitor cell differentiation (or both). (58)
Blockade of electrical activity in dissociated spinal cord cultures results in a significant loss of neurons during a critical period in development. Decreases in neuronal cell numbers and 125I-labeled tetanus toxin fixation produced by electrical blockade with tetrodotoxin (TTX) were prevented by addition of vasoactive intestinal peptide (VIP) to the nutrient medium. This data indicate that under conditions of electrical blockade a neurotrophic action of VIP on neuronal survival can be demonstrated. (6)
It was found that differentiated osteoclasts are equipped with receptors for VIP and that VIP caused an inhibition of osteoclast activity. (49)
VIP can affect anabolic processes in osteoblasts. It was shown that VIP, without affecting cell proliferation, can stimulate osteoblastic ALP biosynthesis and bone noduli formation by a mechanism mediated by cyclic AMP. It appears most likely that anabolic processes in bone are under neurohormonal control. (48)
It was found that neuropeptides (particularly CGRP) have a vasoregulatory role in bone. CGRP mainly mediates relaxation by a direct effect on vascular smooth muscle cells. (50)
It was found that sciatic neurectomy not only inhibited the age-related bone gain, but also reduced the trabecular bone mass by 46%, which was accompanied by decreases in trabecular number, thickness, and node to node density, and an increase in trabecular separation and free end to free end density. This mainly resulted from the decrease in bone formation and the increase in bone resorption. (68)
In contrast to the effects of calcitonin, a marked inhibition of PTH-stimulated bone resorption was still observed after 96 hours in the continued presence of CGRP. (14)
Studies suggest that though CGRP may not be involved in the hormonal control of plasma calcium, the peptide may be an important local regulator of bone cell function. (67)
It appears that the calcitonin-like effects of CGRP, seen both in vivo in the rat bioassay and in vitro in organ cultures, are due to the direct action of CGRP on the osteoclast, probably mediated through the calcitonin receptor. (66)
Neural control of bone metabolism and growth has been suggested, although the identity of participating neurons and neurotransmitters effecting this control has not been established. Immunohistochemical studies demonstrated a system of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers that innervate periosteum and bone in several mammalian species. Thoracic sympathetic chain ganglionectomy resulted in an ipsilateral loss of VIP-immunoreactive fibers in the periosteum of ribs, whereas dorsal root ganglionectomy had no effect. Injection of fast blue into rib periosteum labeled a population of VIP-immunoreactive sympathetic postganglionic neurons. Thus, postganglionic sympathetic neurons may provide an important means by which VIP regulates bone mineralization. (29)
It was found that intact innervation is essential for normal fracture healing because nerve injury induced a large, but mechanically insufficient, fracture callus. (51)
It is postulated that calcitonin gene-related peptide-containing sensory innervation may have a potential importance in the fracture vascular control, angiogenesis and osteogenesis in addition to a protective role against excessive fracture movement. The results are consistent with the neural involvement in bone growth and remodelling. (32)
Substance P and CGRP immunoreactive nerves were found in normal bone, whereas the hypercellular bone marrow of arthritic rats showed a decrease in the density of substance P and CGRP containing fibers. (31)
CGRP-ir axons appeared to reinnervate the eroded surface of metaphyseal bone and cartilage as early as the recruited osteoblasts resume osteogenesis in the postarthritic metaphysis. The observed terminal-target relations in the healthy and diseased bone tissues give an ultramorphological basis for the putative trophic, modulatory actions of CGRP innervation of the bone cells. (34)
The rat lumbar posterior longitudinal ligament is innervated by two, distinctive calcitonin gene-related peptide, immunoreactive nerve networks. In immunoelectronmicroscopy, the fibers of the deep network had numerous free nerve endings, whereas those of the superficial network showed spatial associations with other non-calcitonin gene-related peptide immunoreactive components of the network. In both systems, naked axons not covered by the Schwann cells made close spatial contact with smooth muscle cells: of blood vessels and resident posterior longitudinal ligament fibroblasts. It was concluded that the ultrastructural characteristics of the innervation of the rat posterior longitudinal ligament would be compatible not only with a nociceptive function, but also with neuromodulatory, vasoregulatory, and trophic functions, as has already been established in some visceral organs. (33)
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. In addition, 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 further 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. (4)
It has been noted that low frequency TENS stimulation of nerves causes significant increases in the levels of CGRP. (57) (42)
Takahashi noted that electrical stimulation of the sciatic nerve in anesthetized dogs caused increased blood flow of the stimulated spinal cord and the nerve root. (61)
Gherardini concluded that CGRP, but not lidocaine, significantly increased blood flow after mechanically induced vasospasm. (22) He also found that CGRP was effective in promoting recovery of the microcirculation after mechanically induced ischemia in neurovascular island flaps in rats. (23)
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. (39)(40)(41)
Kaada felt that the primary cause of the improved microcirculation resulting from the electrical stimulation is probably 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. This is 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 stimulation. (37)
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. (38)
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. (54)(18)
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. (5)
There was a significant increase in intracellular cAMP with low-frequency (10 Hz) currents. (60)(43) It was found that VIP caused increased intracellular cAMP. (50)
REFERENCES
1 Andersson GBJ. "Epidemiologic features of chronic low-back pain." Lancet 1999; 354:581-5.
2 Atlas SJ, Chang Y, Kammann E, Keller RB, Deyo RA, Singer DE. Long-term disability and return to work among patients who have a herniated lumbar disc: the effect of disability compensation. J Bone Joint Surg Am 2000; 82:4-15.
3 Bernard GW, Shih C.; "The osteogenic stimulating effect of neuroactive calcitonin gene-related peptide." Peptides 1990 Jul-Aug; 11(4): 625-32
4 Brain SD, Tippins JR, Morris HR, MacIntyre I, Williams TJ "Potent Vasodilator activity of calcitonin gene-related peptide in human skin" J Invest Dermatol. 1986 Oct; 87(4):533-6.
5 Brain SD, Williams TJ. "Substance P regulates the vasodilator activity of calcitonin gene-related peptide." Nature. Vol 335 Sept. 1988 3-5.
6 Brenneman DE, Eiden LE. "Vasoactive intestinal peptide and electrical activity influence neuronal survival." Proc Natl Acad Sci U S A 1986 Feb; 83(4): 1159-62
7 Brewster WJ. Diemel LT, Leach RM, Tomlinson, DR. "Reduced sciatic nerve substance P and calcitonin gene-related peptide in rats with short-term diabetes or central hypoxemia co-exist with normal messenger RNA levels in the lumbar dorsal root ganglia." Neuroscience. 1994 Jan; 58(2): 323-30.
8 Cameron NE, Cotter MA, Low PA. "Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits" Am J Physiol. 1991 Jul; 261(1 Pt 1): E1-8.
9 Cameron NE, Cotter MA, Robertson S. "Chronic low frequency electrical activation for one week corrects nerve conduction velocity deficits in rats with diabetes of three months duration" Diabetologia. 1989 Oct; 32(10): 759-61.
10 Cameron NE, Cotter MA, Robertson S, Maxfield EK "Nerve function in experimental diabetes in rats: effects of electrical stimulation" Am J Physiol. 1993 Feb; 264(2 Pt 1): E161-6.
11 Cherkin DC, Deyo RA, Street JH, Barlow W. "Predicting poor outcomes for back pain seen in primary care using patient's own criteria." Spine 1996; 21:2900-7.
12 Chin-Teng Chung, Chrong-Song Chou, Hung-Jen Ho, San-Kan Lee. "Neurogenic Intermittent Claudication Related to Spinal Stenosis." Chin Med J (Taipei) 2000; 63:809-815.
13 Coste J, Delecoeuillerie G, Cohen de Lara A, Le Parc JM, Paolaggi HB. "Clinical course and prognostic factors in acute low back pain: an inception cohort study in primary care practice." BMJ 1994; 308:577-80.
14 D'Souza SM, MacIntyre I, Girgis SI, Mundy GR. "Human synthetic calcitonin gene-related peptide inhibits bone resorption in vitro." Endocrinology 1986 Jul; 119(1): 58-61.
15 Dawidson K, Angmar-Mansson B, Blom M, Theodorsson E, Lundeberg T "The influence of sensory stimulation (acupuncture) on the release of neuropeptides in the saliva of healthy subjects." Life Sci. 1998; 63(8): 659-74.
16 Deyo RA, Weinstein JN. "Low back pain." N Engl J Med 2001; 344:363-70.
17 Diemel LT, Stevens EJ, Willars GB, Tomlinson DR. "Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of rats with experimental diabetes; effects of insulin and aldose reductase inhibition." Neurosci Lett. 1992 Mar 30; 137(2): 253-6.
18 Fahrenkrug J, Emson PC. "Vasoactive intestinal polypeptide: functional aspects" Br Med Bull. 1982 Sep; 38(3): 265-70. Review.
19 Fisher, M.A. "The contemporary role of F-wave studies." Muscle&Nerve 8/97; 1098-1101)
20 Gherardini G, Evans GR, Theodorrsson E, Gurlek A, Milner SM, Palmer B, Lundeberg T. "Calcitonin gene-related peptide in experimental ischemia. Implication of an endogenous anti-ischemic effect." Ann Plast Surg. 1996 Jun; 36(6): 616-20.
21 Gherardini G, Gurlek A, Milner SM, Martarassso A, Evans GR, Jernbeck J, Lundeberg T. "Calcitonin gene-related peptide improves skin flap survival and tissue inflammation". Neuropeptides. 1998 Jun; 32(3): 269-73.
22 Gherardini G, Jernbeck J, Samuelson U, Heden P. "Effects of calcitonin gene-related peptide and lidocaine on mechanically-induced vasospasm in a rat island flap." J Reconstr Microsurg. 1995 May; 11(3): 179-83.
23 Gherardini G, Lundeberg T, Matarasso A, Michaels B, Gazelius B, Brodda-Jansen G, Samuelson U. "Calcitonin gene-related peptide increases microcirculation after mechanically induced ischemia." Ann Plast Surg. 1995 Aug; 35(2): 178-83.
24 Gibson JNA, Grant IC, Waddell G. "The Cochrane review of surgery for lumbar disc prolapse and degenerative lumbar spondylosis." Spine 1999; 24:1820-32.
25 Guido E. "Effects of Sympathetic Therapy on Chronic Pain in Peripheral Neuropathy Subjects." American Journal of Pain Management 2002; Jan 12(1): 31-34.
26 Halderman,S. "Low Back Pain Current Physiologic Concepts." Neurologic Clinics of North America 1999; 17:1-15.
27 Hart LG, Deyo RA, Cherkin DC. "Physician office visits for low back pain: frequency, clinical evaluation, and treatment patterns from a U.S. national survey." Spine 1995; 20:11-9.
28 Henning A., Stalberg E.,Falck, B. "F-wave latency, the most sensitive nerve conduction parameter in patients with diabetes mellitus." Muscle&Nerve 10/97; 1296-1302
29 Hohmann EL, Elde RP, Rysavy JA, Einzig S, Gebhard RL. "Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers." Science 1986 May 16; 232(4752): 868-71.
30 Hotta H, Sato A, Sato Y, Uchida S. "Stimulation of saphenous afferent nerve produces vasodilation of the vasa nervorum via an axon reflex-like mechanism in the sciatic nerve of anesthetized rats." Neurosci Res. 1996 Feb; 24(3): 305-8.
31 Hukkanen M, Konttinen YT, Rees RG, Gibson SJ, Santavirta S, Polak JM. "Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers." J Rheumatol 1992 Aug;19(8):1252-9
32 Hukkanen M, Konttinen YT, Santavirta S, Paavolainen P, Gu XH, Terenghi G, Polak JM. "Rapid proliferation of calcitonin gene-related peptide-immunoreactive nerves during healing of rat tibial fracture suggests neural involvement in bone growth and remodelling." Neuroscience 1993 Jun; 54(4): 969-79
33 Imai S, Konttinen YT, Tokunaga Y, Maeda T, Hukuda S, Santavirta S. "An ultrastructural study of calcitonin gene-related peptide-immunoreactive nerve fibers innervating the rat posterior longitudinal ligament. A morphologic basis for their possible efferent actions." Spine 1997 Sep 1; 22(17): 1941-7.
34 Imai S, Rauvala H, Konttinen YT, Tokunaga T, Maeda T, Hukuda S, Santavirta S. "Efferent targets of osseous CGRP-immunoreactive nerve fiber before and after bone destruction in adjuvant arthritic rat: an ultramorphological study on their terminal-target relations." J Bone Miner Res 1997 Jul; 12(7): 1018-27.
35 Jager K, Muench R, Seifert H, Beglinger C, Bollinger A, Fischer JA "Calcitonin gene-related peptide (CGRP) causes redistribution of blood flow in humans." Eur J Clin Pharmacol. 1990; 39(5): 491-4.
36 Jansen GB, Torkvist L, Lofgren O, Raud J, Lundeberg T. "Effects of calcitonin gene-related peptide on tissue survival, blood flow and neutrophil recruitment in experimental skin flaps." Br J Plast Surg. 1999 Jun; 52(4): 299-303.
37 Kaada B "Promoted healing of chronic ulceration by transcutaneous nerve stimulation (TNS)" Vasa. 1983; 12(3): 262-9.
38 Kaada, B "Successful treatment of esophageal dysmotility and Raynaud's phenomenon in systemic sclerosis and achalasia by transcutaneous nerve stimulation. Increase in plasma VIP concentration." Scand J Gastroenterol. 1987 Nov; 22(9): 1137-46.
39 Kaada B "Systemic sclerosis: successful treatment of ulcerations, pain, Raynaud's phenomenon, calcinosis, and dysphagia by transcutaneous nerve stimulation. A case report." Acupunct Electrother Res. 1984; 9(1): 31-44.
40 Kaada B "Vasodilation induced by transcutaneous nerve stimulation in peripheral ischemia (Raynaud's phenomenon and diabetic polyneuropathy)." Eur Heart J. 1982 Aug; 3(4): 303-14.
41 Kaada B, Lygren I "Lower plasma levels of some gastrointestinal peptides in Raynaud's disease. Influence of transcutaneous nerve stimulation." Gen Pharmacol.1985; 16(2): 153-6.
42 Kashiba H, Ueda Y "Acupuncture to the skin induces release of substance P and calcitonin gene-related peptide from peripheral terminals of primary sensory neurons in the rat." Am J Chin Med. 1991; 19(3-4): 189-97.
43 Knedlitshek G, Noszvai-Nagy M, Meyer-Waarden H, Schimmelpfeng J, Weibezahn KF, Dertinger H. "Cyclic AMP response in cells exposed to electric fields of different frequencies and intensities." Radiat Environ Biophys. 1994; 33(2): 141-7.
44 Kohara N, Kimura J, Kaji R, Goto Y, Ishii J. "Inter-trial variability of nerve conduction studies, multicenter analysis." Electroencephalogr Clin Neurophysiol 1995;97:566
45 Lindberger M, Schroder HD, Schultzberg M, Kristensson K, Persson A, Ostman J, Link H. "Nerve fibre studies in skin biopsies in peripheral neuropathies." I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. J Neurol Sci. 1989 Nov; 93(2-3): 289-96.
46 Ling C, Liu Z, Welin M, Ordeberg G, Nyberg F. "Low calcitonin gene-related, peptide-like immunoreactivity in cerebrospinal fluid from chronic pain patients." Neuropeptides 1999; 33(6) 517-521.
47 Linsinsk P, "Surface EMG in chronic low back pain." Eur Spine 2000 Dec; 9(6): 559-62
48 Lundberg P, Bostrom I, Mukohyama H, Bjurholm A, Smans K, Lerner UH. "Neuro-hormonal control of bone metabolism: vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules." Regul Pept 1999 Nov 30; 85(1): 47-58
49 Lundberg P, Lie A, Bjurholm A, Lehenkari PP, Horton MA, Lerner UH, Ransjo M. "Vasoactive intestinal peptide regulates osteoclast activity via specific binding sites on both osteoclasts and osteoblasts." Bone 2000 Dec; 27(6): 803-10
50 Lundgaard A, Aalkjaer C, Bjurholm A, Mulvany MJ, Hansen ES. "Vasorelaxation in isolated bone arteries. Vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and bradykinin studied in pigs." Acta Orthop Scand 1997 Oct; 68(5): 481-9
51 Madsen JE, Hukkanen M, Aune AK, Basran I, Moller JF, Polak JM, Nordsletten L. "Fracture healing and callus innervation after peripheral nerve resection in rats." Clin Orthop 1998 Jun;(351): 230-40
52 O'Dorisio MS, Wood CL, Wenger GD, Vassalo LM. "Cyclic AMP-dependent protein kinase in Molt 4b lymphoblasts: identification by photoaffinity labeling and activation in intact cells by vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI)." J Immunol. 1985 Jun; 134(6): 4078-86.
53 Rossi R, Hohansson O. "Cutaneous innervation and the role of neuronal peptides in cutaneous inflammation: a minireview." Eur J Dermatol. 1998 Jul-Aug;8(5): 299-306. Review.
54 Said SI "Vasoactive intestinal polypeptide (VIP): Current Status" Peptides. 1984 Mar-Apr; 5(2): 143-50. Review.
55 Sato A, Sato Y, Shimura M, Uchida S. "Calcitonin gene-related peptide produces skeletal muscle vasodilation following antidromic stimulation of unmyelinated afferents in the dorsal root in rats." Neurosci Lett. 2000 Apr 7; 283(2): 137-40.
56 Sato A, Sato Y, Uchida S. "Blood flow in the sciatic nerve is regulated by vasoconstrictive and vasodilative nerve fibers originating from the ventral and dorsal roots of the spinal nerves." Neurosci Res. 1994 Dec; 21(2): 125-33.
57 Saurstein K, Klede M. Hilleges M, Schmelz M. "Electrically evoked neuropeptide release and neurogenic inflammation differ between rat and human skin." J Physiol. 2000 Dec 15; 529 Pt3: 803-10.
58 Shih C, Bernard GW. "Calcitonin gene related peptide enhances bone colony development in vitro." Clin Orthop 1997 Jan;(334): 335-44
59 Shindo H, Tawata M, Onaya Tl. "Reduction of cyclic AMP in the sciatic nerve of rats made diabetic with streptozotocin and the mechanism involved." J Endocrinol. 1993 Mar; 136(3): 431-8.
60 Sontag W, Dertinger H. "Response of cytosolic calcium, cyclic AMP, and cyclic GMP in dimethylsulfoxide-differentiated HL-60 cells to modulated low frequency electric currents." Bioelectromagnetics. 1998; 19(8): 452-8.
61 Takahashi K, Nomura S, Tomita K, Matsumoto T "Effects of peripheral nerve stimulation on the blood flow of the spinal cord and the nerve root." Spine. 1988 Nov; 13(11): 1278-83.
62 Terata K, Coppey LJ, Davidson EP, Dunlap JA, Gutterman DD, Yorek MA "Acetylcholine-induced arteriolar dilation is reduced in streptozotocin-induced diabetic rats with motor nerve dysfunction." Br J Pharmacol. 1999 Oct; 128(3): 837-43.
63 Umeda F, Noda K, Ono H, Chijiiwa Y, Nawata H. "Decreased Vasoactive Intestinal Polypeptide (VIP) Level in Cerebrospinal Fluid from Diabetic Patients with Neuropathy." Fukuoka Igaku Zasshi. 1991 Jan; 82(1):17-20.
64 Winter A "The use of Transcutaneous Electrical Stimulation (TNS) in the Treatment of Multiple Sclerosis." Journal of Neurosurgical Nursing December. Vol. 8, No. 2
65 Yamoto M, Sobue G, Li M, Mitsuma T, Kimata K, Yamada Y. "cAMP-dependent differential regulation of extracellular matrix (ECM) gene expression in cultured rat Schwann cells." Brain Res. 1994 Aug 8; 653(1-2): 335-9.
66 Zaidi M, Chambers TJ, Gaines Das RE, Morris HR, MacIntyre I. "A direct action of human calcitonin gene-related peptide on isolated osteoclasts." J Endocrinol 1987 Dec; 115(3): 511-8
67 Zaidi M, Fuller K, Bevis PJ, GainesDas RE, Chambers TJ, MacIntyre I. "Calcitonin gene-related peptide inhibits osteoclastic bone resorption: a comparative study." Calcif Tissue Int 1987 Mar; 40(3): 149-54
68 Zeng QQ, Jee WS, Bigornia AE, King JG Jr, D'Souza SM, Li XJ, Ma YF, Wechter WJ. "Time responses of cancellous and cortical bones to sciatic neurectomy in growing female rats." Bone 1996 Jul; 19(1): 13-21
69 Zochodne DW, Ho LT "Influence of perivascular peptides on endoneurial blood flow and microvascular resistance in the sciatic nerve of the rat." J Physiol. 1991 Dec; 444:615-30.
