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. • • • 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 • …