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HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY

HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY. PHYSICS OF ELECTROMAGNETIC WAVES.

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HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY

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  1. HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY

  2. PHYSICS OF ELECTROMAGNETIC WAVES • Energy radiated in the form of a wave as a result of the motion of electric charges. A moving charge gives rise to a magnetic field, and if the motion is changing (accelerated), then the magnetic field varies and in turn produces an electric field. These interacting electric and magnetic fields are at right angles to one another and also to the direction of propagation of the energy.

  3. ELECTROMAGNETIC WAVES SPECTRUM MW therapy range

  4. Millimeter waves applications

  5. Partial list of diseases claimed to be successfully treated with MW • Gastrointestinal diseases • Various blood circulation disorders • Chronic and acute pulmonary diseases • Various types of cancer • Endocrine system disorders • Cerebral palsy • Opioid, alcohol and nicotine dependencies • Neuropathic pain conditions • Skin and bones diseases

  6. Reported therapeutic potentials of mw • Sedative and analgesic effects • Anti-inflammatory and Immune system modulation • Repair-stimulating action

  7. Why is the western medicine skeptical? • Qualitative description of the received results in most clinical reports • Absence of Sham-controls and “blind” settings in almost all publications • Lack of sufficient experimental details in reports • Physiological mechanisms of the treatment are unclear

  8. Human volunteer study: cold-pressor test Changes in tolerance to the cold-induced pain after a single MW exposure * A.Radzievsky et al, Anesth&Analg, 1999; 88; 836-840

  9. Types of Pain Experimental equivalent in our experiments Acute pain Activation of nociceptive transducers in the presence of tissue damage (Typically < 1 month) Hot water Tail-Flick Test(hTFT) Chronic non-neuropathic pain (Pain persisting > 1 month or recurring for > 3 months) Cold water Tail Flick Test(cTFT) Chronic neuropathic pain (Pain initiated or caused by a primary lesion or dysfunction in the nervous system) Chronic Constriction Injury(CCI) of the sciatic nerve Types of pain and their experimental equivalents in our experiments

  10. Experimental setup • Animals: • Male Swiss-Webster mice; 20-25gr • Mice are restrained • Endpoint of the test: • Latency of tail withdrawal from the ice-cold or hot (52oC) water • “Blind” experimental settings • Two researchers are performing the test. One exposes the mice, and the other conducts the cTFT

  11. Experimental setup: exposure to MW • Electromagnetic MW characteristics: • Frequency – 61.22 GHz • (G4-142) • Output Power 30 mW • Peak Power Density 56 mW/cm2 • Average Incident • Power Density – 13.3 mW/cm2 • Duration – 15 min • Area of exposure - Nose

  12. Acute pain Hot water tail-flick test Radzievsky A. et al, 2004; IEEE Trans. Plasma Sci. 32;4;1634-1643

  13. Chronic pain * * * Radzievsky A. et al, 2004; IEEE Trans. Plasma Sci. 32;4;1634-1643

  14. Heating during MWT ΔT 1oC ΔT = 0.5OC during 55 sec of the exposure 0oC Max ΔT during 15 min of exposure = 1.2 OC

  15. Specificity of MWT Hypoalgesia in cTFT following MWT and exposure to the Holmium YAG laser Radzievsky A. et al, 2004; IEEE Trans. Plasma Sci. 32;4;1634-1643

  16. What parameters of MWT are most effective? cTFT: MW Frequency * * * x * x * x

  17. What parameters of MWT are most effective? cTFT: MW Power * * M.Rojavin et al, 2000; Int.J.Radiat.Biol., 76, p.575-579

  18. What parameters of MWT are most effective? cTFT: Duration of exposure

  19. What parameters of MWT are most effective? cTFT: Area of exposure * * A.Radzievsky et al, 2000; Life Sci., 66, p.2101-2111

  20. What parameters of MWT are most effective? cTFT: Area of exposure Sciatic nerve cut • 3 - n. femoralis • 5 - n. saphenus • 7 - n. ischiadicus • 11 - n. fibularis • 12 - n. fibularissupf. • 13 - n. fibularisprof. • 14 - n. tibialis

  21. What parameters of MWT are most effective? cTFT: Area of exposure * A.Radzievsky et al, 2001; Life Sci., 68, p.1143-1151

  22. Types of Pain Experimental equivalent in our experiments Acute pain Activation of nociceptive transducers in the presence of tissue damage (Typically < 1 month) Hot water Tail-Flick Test(hTFT) Chronic non-neuropathic pain (Pain persisting > 1 month or recurring for > 3 months) Cold water Tail Flick Test(cTFT) Chronic neuropathic pain (Pain initiated or caused by a primary lesion or dysfunction in the nervous system) Chronic Constriction Injury(CCI) of the sciatic nerve Types of pain and their experimental equivalents in our experiments

  23. Experimental model of neuropathic pain in mice Unilateral Chronic Constriction Injury (CCI) of the common sciatic nerve Anesthetized mouse before the surgery Two ligatures around the common sciatic nerve

  24. Experimental model of neuropathic pain in mice Unilateral Chronic Constriction Injury (CCI) of the common sciatic nerve Control mouse Neurological defect in 30 days following CCI Sciatic nerve in 30 days after CCI

  25. Wire surface test Indexes of the WST (5 min of observation) • Number of Paw Protective Movements (PPM) in horizontal position • Number of PPM in vertical position • Total Time (TT) the injured paw was held over the surface • Vertical Activity (VA) • Number of times the animal is taking a vertical position.

  26. Time schedule of the experiment 10 MWT Training 0 Test Training 5 15 20 25 30 40 10 45 35 0 Days Arrival Surgery Experimental WST Baseline WST

  27. Hypoalgesic effect of MWT in the murine model of neuropathic pain * * Radzievsky A.et all, IEEE Trans Plasma Sci. 2004 ;32, pp. 1634-1643.

  28. Endogenous opioids in the MWT-induced hypoalgesia cTFT: Pretreatment with Naloxone *

  29. Endogenous opioids in the MWT-induced hypoalgesia Major types of opioid receptors • mu-opioid receptor (MOR) • β-endorphin, endomorphines 1&2 • delta-opioid receptor (DOR) • Enkephalin • kappa-opioid receptor (KOR) • dynorphin

  30. Endogenous opioids in the MWT-induced hypoalgesia Opioid receptor functions •  Control of: • Nociception • Respiration • Cardiovascular functions • Intestinal transit • Feeding • Learning and memory • Locomotor activity • Thermoregulation • Hormone secretion • Immune functions •  Control of: • Nociception • Motor integration • Gastro-Intestinal motility • Olfaction • Respiration • Cognitive functions • Mood driven behavior • Immune functions •  Control of: • Nociception • Diuresis • Feeding • Neuroendocrine secretion • Immune functions B. Dhawan et al, 1996, Pharm. Review, 48

  31. Endogenous opioids in the MWT-induced hypoalgesia Opioid pharmacology and functions (experiments in “knockout “mice) DPDPE U50,488H Morphine deltropine MOR DOR KOR hypoalgesia dysphoria reward dependence From Kieffer & Gaveriaux-Ruff, 2002

  32. Endogenous opioids in the MWT-induced hypoalgesia cTFT: Pretreatment with Mu OR blocker β FNA A.Radzievsky at al, Bioelectromagnetics, 2008 ;29(4):284-95.

  33. Endogenous opioids in the MWT-induced hypoalgesia cTFT: Pretreatment with Delta OR blocker NTI A.Radzievsky at al, Bioelectromagnetics, 2008 ;29(4):284-95.

  34. Endogenous opioids in the MWT-induced hypoalgesia cTFT: Pretreatment with Kappa OR blocker nor-BNI A.Radzievsky at al, Bioelectromagnetics, 2008 ;29(4):284-95.

  35. Endogenous opioids in the MWT-induced hypoalgesia Enkephaline(DOR agonist) content in various parts of the murine brain following MWT A.Radzievsky at al, Bioelectromagnetics, 2008 ;29(4):284-95.

  36. Endogenous opioids in the MWT-induced hypoalgesia MWT MOR DOR KOR ? ? hypoalgesia dysphoria reward dependence

  37. Mwt-induced hypoalgesia: Conclusions • MWT-induced hypoalgesia is an objective and reproducible biological effect • The efficacy of the MWT depends on MW physical parameters and the area of the exposure • Endogenous opioids (delta and kappa opioid receptors and agonists in particular) are involved in the MWT-induced hypoalgesia • MWT is most effective in chronic types of pain

  38. Possible clinical application of mwt in patients with neuropathic pain • 50 patients (age 18-70 y.o.) with various types of neuropathic pain will be randomly divided into MWT- and Sham-MWT groups (25 patients in each) • Ten sessions of MWT (20 min each) will be conducted • Pain visual analog scale will be applied 4 times: before the treatment, after the 5th MWT (middle of the treatment); after the 10th MWT, and in 10 days after the treatment is over • Functional MRI before, during, and 10 days after the course of MWT?

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