Optimization of static magnetic fields for therapeutical purposes

1
Optimization of static magnetic fields for
therapeutical purposes

• presentation for
• Entre per le Nuove
• Tecnologie, lEnergia e lAmbiente (ENEA),
• Centro Ricerche Casaccia,
• January 18, 2008
• János László, PhD (http//e-comers.net)

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• Preliminaries
• Results
• Tasks

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Power lines, mobile telephones and MR have become
part of our everyday life, the estimate of their
adverse (and beneficial ?) health-effects has got
extreme importance during the past some
decades. WHO initiated a program called
Environmental Health Criteria in 1973. The most
recent experiences were collected and published
in 2006. The authoring group admitted that they
lacked reproducible, evidence-based experimental
data in many subfields.
4
In Cooperation, Theme 1, Health of the Work
Programme 2007 of FP7 of the European Union, it
reads Emphasis will be put on translational
research (translation of basic discoveries into
clinical applications including scientific
validation of experimental results), the
development and validation of new therapies,
methods for health promotion and prevention
including promotion of child health, healthy
ageing, diagnostic tools and medical
technologies, as well as sustainable and
efficient health care systems. (underlining by
JL)
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magnet matrices
brake trigger
rails
140 mm
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• Preliminaries
• Results
• Tasks

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1st question Does static magnetic field have an
antinociceptic/analgesic effect at all? i) The
experimental assay is the writhing test in mice,
the pain is elicited by ip acetic acid
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Effect of static magnetic field (SMF) and
optimized static magnetic field (oSMF) on the
average writhing number of mice, if pain is
induced by 0.6 ip acetic acid
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2nd question Is acetic acid the sole
responsible, or other irritating chemicals, e.g.,
epsom salt (MgSO4 7H2O) can do the same?
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The effect of oSMF on the average writhing number
of mice (n12, 6 resp.), if pain is induced by
ip epsom salt
plt0.002
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3rd question What is the definition of the
antinociceptive activity/analgesic effect?
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Antinociceptive activity/analgesic effect of SMF
and oSMF in mice, if the irritant is either
acetic acid, or epsom salt
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Antinociceptive activity/analgesic effect of oSMF
in mice, if the irritant is acetic acid, as
compared to different NSAIDs in the same test
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4th question How does the effect depend on the
parameters of the SMF (generator)?
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Antinociceptive activity/analgesic effect of
different SMF generators in mice
oSMF
SMF
1 T hom.
one-sided
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5th question Does the sc injection of saline
make a difference in the effect?
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The effect of SMF and oSMF on the average
writhing number of mice, if pain is induced by ip
acetic acid and saline is injected sc in the mice
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6th question What is responsible for the effect?
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endogenous cannabinoid system?
CB1 KO mice
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endogenous opioid system?
naloxone 1 mg/kg sc
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endogenous opioid system?
naloxone 1 mg/kg sc
µ-opioid receptors?
naloxone 0.2 mg/kg sc
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endogenous opioid system?
naloxone 1 mg/kg sc
d-opioid receptors?
µ-opioid receptors?
naltrindole sc
naloxone 0.2 mg/kg sc
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endogenous opioid system?
naloxone 1 mg/kg sc
?-opioid receptors?
µ-opioid receptors?
d-opioid receptors?
naltrindole sc
norbinal- torphymine sc
naloxone 0.2 mg/kg sc
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capsaicine- sensitive fibers?
mechanical allodynia, formaline assay with
resiniferatoxin desensibilitation
mechanical allodynia, formaline assay
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7th question What is the place of action?
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The effect of SMF on the average writhing number
of mice, that got icv non-selective opioid
receptor antagonist naloxone (NX)
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The effect of SMF on the average writhing number
of mice, that got sc non-selective, peripheral
acting opioid receptor antagonist naloxone methyl
iodide (NX-mi)
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8th question Is there any retard effect? What
are the dynamics?
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The effect of oSMF on the average writhing number
of mice, that got ip acetic acid when it is shown
by the arrow and were exposed to different
durations
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• Remember the 1st question?
• Does static magnetic field have an
  antinociceptic/analgesic effect at all?
• The experimental assay is the writhing test in
  mice, the pain is elicited by ip acetic acid

• The experimental assay is the formalin test in
  mice

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The effect of oSMF on the mechanonocifensive
behavior of mice, that have an ipl
formalin-induced inflammation
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• Remember the 1st question?
• Does static magnetic field have an
  antinociceptic/analgesic effect at all?
• The experimental assay is the writhing test in
  mice, the pain is elicited by ip acetic acid

• The experimental assay is the formalin test in
  mice

• The experimental assay is the resiniferatoxin test

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The effect of oSMF on the mechanical allodynia of
mice, that have an ipl resiniferatoxine-induced
inflammation
plt0.05
mechanical allodynia ()
control
oSMF
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9th question Is a muscle relaxation effect
included? Coordination and motor function test
rotarod test
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The effect of oSMF on the muscle relaxation of
mice as performed on the rotarod drum before or
after a 30 min exposure to the SMF, or control in
a sham box
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10th question Is there an effect of SMF on the
gastric tract? The gastric lesions are induced by
alcohol per os.
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The effect of SMF and oSMF on the gastric lesions
induced by alcohol per os in mice (n36, 24, 18
resp.)
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Raw optical view of the alcohol-induced gastric
ulcers in the stomach of untreated (photos to the
left) and oSMF-exposed mice (photos to the right)
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11th question Is there an effect of SMF on the
CNS? The test to prove this is an elevated plus
maze test.
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The effect of oSMF on the performance of mice in
an elevated plus maze (n 10, 10)
pmingt0.22
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• Answers
• Static magnetic fields may induce an
  antinociceptive activity/analgesic effect of up
  to 83.
• The effect of saline cannot be identified in
  comparison to control by either sc or icv
  administration.
• The endogenous opioid system is responsible for
  the effect of SMF.
• The liberalization of µ-opioid-receptors seems to
  be important.
• C-fibers also play a role in the inhibition of
  pain and inflammation.
• The effect is not related to muscle relaxation.
• The effect may be peripheral.
• The wound-healing effect is undeniable.

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• Publications (peer-reviewed)
• J László, J Reiczigel, L Székely, A Gasparics, I
  Bogár, L Bors, B Rácz, K Gyires. 2006.
  Optimization of the static magnetic field
  parameters improves analgesic effect in mice.
  Bioelectromagnetics, 28(8)615-627.
• J László, K Gyires. 2006. Static magnetic
  field-induced antinociceptive activity (analgesic
  effect) in mice may be mediated by the opioid
  system, Abstract, XVth World Congress of
  Pharmacology, Acta Pharmacologica Sinica 7(1)
  113.
• K Sándor, Z Helyes, K Gyires, J Szolcsányi, J
  László. 2006. Static magnetic field-induced
  antinociceptive effect and the involvement of
  capsaicin-sensitive sensory nerves in this
  mechanism. Life Sciences 8197-102.
• K Gyires, B Rácz, Z Zádori, J László. 2007.
  Static magnetic field induces an opioid-mediated
  analgesic action in the writhing test in mice.
  Accepted at Bioelectromagnetics.
• J László, K Gyires. 2007. 3 T MR significantly
  inhibits pain in the writhing test in mice.
  Submitted to NMR in Biomedicine.

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Publications (non peer-reviewed)

• Rácz B. 2006. Sztatikus mágneses tér (SMT) hatása
  a kísérletes fájdalomérzésre egéren, Semmelweis
  Egyetem TDK, III. díj és a Magyar Farmakológiai
  Társaság Különdíja.
• Rácz B. 2006. Sztatikus mágneses tér (SMT) hatása
  a kísérletes fájdalomérzésre egéren, eloadás,
  Farmakológiai Társaság Szimpóziuma, Pécs.
• Domokos C, Hajagos I. 2006. 3-dimenziós mágneses
  tér szimulálása, Szegedi Egyetem TDK, I. díj.
• C Domokos, I Hajagos. 2006. Computation and
  visualization of magnetic fields, in Proceedings
  of Central European Seminar on Computer Graphics
  for Students, eloadás, Castá-Papiernicka, Szlovák
  Köztársaság.

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• Preliminaries
• Results
• Tasks

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We research here
100
You research here and there
from Malmivuo J., Plonsey R Bioelectromagnetism,
Oxford University Press, New York, Oxford 1995.
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Review of SMF in in-vitro models from 1989 to 2007
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Review of SMF in in-vivo models from 1984 to 2006
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Where we cooperate
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Thanks for your attention!