Hypoalgesic effects of millimeter wave therapy
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HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY. PHYSICS OF ELECTROMAGNETIC WAVES.

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HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY

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Hypoalgesic effects of millimeter wave therapy

HYPOALGESIC EFFECTS OF MILLIMETER WAVE THERAPY


Physics of electromagnetic waves

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.


Electromagnetic waves spectrum

ELECTROMAGNETIC WAVES SPECTRUM

MW therapy

range


Millimeter waves applications

Millimeter waves applications


Partial list of diseases claimed to be successfully treated with mw

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


Reported therapeutic potentials of mw

Reported therapeutic potentials of mw

  • Sedative and analgesic effects

  • Anti-inflammatory and Immune system modulation

  • Repair-stimulating action


Why is the western medicine skeptical

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


Human volunteer study cold pressor test

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


Types of pain and their experimental equivalents in our experiments

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


Experimental setup

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


Experimental setup exposure to mw

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


Acute pain

Acute pain

Hot water tail-flick test

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


Chronic pain

Chronic pain

*

*

*

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


Heating during mwt

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


Specificity of mwt

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


What parameters of mwt are most effective

What parameters of MWT are most effective?

cTFT: MW Frequency

*

*

*

x

*

x

*

x


What parameters of mwt are most effective1

What parameters of MWT are most effective?

cTFT: MW Power

*

*

M.Rojavin et al, 2000; Int.J.Radiat.Biol., 76, p.575-579


What parameters of mwt are most effective2

What parameters of MWT are most effective?

cTFT: Duration of exposure


What parameters of mwt are most effective3

What parameters of MWT are most effective?

cTFT: Area of exposure

*

*

A.Radzievsky et al, 2000; Life Sci., 66, p.2101-2111


What parameters of mwt are most effective4

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


What parameters of mwt are most effective5

What parameters of MWT are most effective?

cTFT: Area of exposure

*

A.Radzievsky et al, 2001; Life Sci., 68, p.1143-1151


Types of pain and their experimental equivalents in our experiments1

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


Experimental model of neuropathic pain in mice

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


Experimental model of neuropathic pain in mice1

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


Wire surface test

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.


Time schedule of the experiment

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


Hypoalgesic effect of mwt in the murine model of neuropathic pain

Hypoalgesic effect of MWT in the murine model of neuropathic pain

*

*

Radzievsky A.et all, IEEE Trans Plasma Sci. 2004 ;32, pp. 1634-1643.


Endogenous opioids in the mwt induced hypoalgesia

Endogenous opioids in the MWT-induced hypoalgesia

cTFT: Pretreatment with Naloxone

*


Endogenous opioids in the mwt induced hypoalgesia1

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


Endogenous opioids in the mwt induced hypoalgesia2

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


    Endogenous opioids in the mwt induced hypoalgesia3

    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


    Endogenous opioids in the mwt induced hypoalgesia4

    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.


    Endogenous opioids in the mwt induced hypoalgesia5

    Endogenous opioids in the MWT-induced hypoalgesia

    cTFT: Pretreatment with Delta OR blocker NTI

    A.Radzievsky at al, Bioelectromagnetics, 2008 ;29(4):284-95.


    Endogenous opioids in the mwt induced hypoalgesia6

    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.


    Endogenous opioids in the mwt induced hypoalgesia7

    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.


    Endogenous opioids in the mwt induced hypoalgesia8

    Endogenous opioids in the MWT-induced hypoalgesia

    MWT

    MOR

    DOR

    KOR

    ?

    ?

    hypoalgesia

    dysphoria

    reward

    dependence


    Mwt induced hypoalgesia conclusions

    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


    Possible clinical application of mwt in patients with neuropathic pain

    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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