Transcript Occipital Nerve Stimulation Suppresses Nociception

Occipital Nerve Stimulation
Suppresses Nociception
Michael Oshinsky, PhD*
Harumitsu Hirata, PhD *
Christopher Poletto, PhD¥
* Thomas Jefferson University
¥ Medtronic Neuromodulation
Occipital Nerve Stimulation
• ONS is an emerging therapy for chronic
daily headache (e.g. chronic migraine)
• Migraine pain may result from sensitization
of the trigeminal nucleus caudalis
• This study quantifies the effects of ONS on
these neurons in a rat model of central
trigeminal sensitization
Migraine/ONS Anatomy
Rodent MOA Study
•
Objective: Measure the effects of ONS on the sensitization of second
order sensory neurons in the trigeminal nucleus caudalis (TNC) in a rat
model of migraine.
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Study Design and Scope:
Record from WDR neurons in the TNC
Receptive fields include face and dura
– Phase I – 20 Rats
• Determine the stimulus parameters to stimulate only A-beta fibers.
• Measure effect of ONS on evoked sensory responses in WDR neurons in the TNC
– Brush
– Pinch
– Phase II – 16 Rats
• Test the effect of ONS on same neurons following the application of
nociceptive/sensitizing stimulus (capsaicin) on the dura.
• Saline control group to blind investigators to the presence of the stimulus.
Phase I
Record here
TNC
GON
Tactile stim. here
Electrical stim. here
Results: Fiber Selectivity
T.2 ms
3T.2 ms
3T2.5 ms
A
C
Phase I Results
• Fiber selectivity was possible
– 0.2 ms pulses
• ONS had no effect on normal evoked
responses
– No increase or decrease in action potentials
evoked by:
• Brush
• Nociceptive pinch
Phase II
Capsaicin here
Record here
TNC
GON
Tactile stim. here
Electrical stim. here
Capsaisin Caused Sensitization
but
ONS Reduced Nociception
in the presence of Sensitization
ONS Reduced Nociception
p = 0.006
N=6
N=6
N=6
N=6
Conclusions
• ONS has no effect on evoked responses
when there is no sensitization
– Consistent with no facial numbness
• ONS suppresses nociception when there
is sensitization
– Consistent with reduced headache pain
Many Questions Remain
• How is nociception supressed?
– Neurotransmitters involved?
• GABA, Serotonin, Dopamine, norepinephrine?
– Pathways involved?
• Local segmental suppression?
• Descending modulation?
• Combination?
• Are there also direct effects upstream (e.g. thalamus)?
• What stimulation parameters improve suppression?
– Frequency
– On/Off cycle
– Nerve target
• …