Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on

experimental heat pain

Taras Usichenko

Department of Anesthesia, McMaster University, Hamilton, Canada

Klinik für Anästhesiologie und Intensivmedizin, Universitätsmedizin Greifswald

Bullet Points

• transcutaneous vagal nerve stimulation (TVNS) is a promising method in treatment of pain

• cerebral effects of experimental pain under TVNS vs. placebo were

studied using functional MRI

• TVNS reduced neuronal activation of the areas involved in emotional and cognitive pain regulation as well as the hypothalamus

• Epilepsia*

• Depression*

• Obesity

• Anxiety disorders

• Chronic pain

* FDA recommendation

George et al. Exp Rev Neurother 2007;7:63-74

Background: vagal nerve stimulation

George et al. Exp Rev Neurother 2007;7:63-74

Non-invasive transcutaneous vagal nerve stimulation (TVNS)

Device for non-invasive TVNS

http://www.cerbomed.com/

• Epilepsia*

• Depression*

• Obesity

• Anxiety disorders

• Chronic pain

* FDA recommendation

Potential mechanism of TVNS

Peuker & Filler. Clin Anatomy 2002;15:35-37

fMRI response of brainstem to electrical stimulation of cymba conchae in 12 volunteers

PAG: Periaqueductal gray PBA: parabrachial area

Frangos et al. Brain Stimul 2015;8:624-36

• nucleus solitarius • principal sensory and • spinal trigeminal nuclei

Ossipov et al. J Clin Invest 2010;120:3779-87

Descending pain modulation (green)

Descending pain inhibitory circuitry

Ascending pain pathway (red)

Noxious stimuli

Aim of the study

Ascending pain pathway (red)

To investigate: • the reaction of healthy volunteers to

experimental heat pain • and cerebral fMRI responses under TVNS

in comparison with placebo intervention

Ascending pain pathway (red)

Methods: experimental setup

3T MRI Scanner

- 20 healthy volunteers in 2 sessions: TENS and Placebo in crossover manner

Experimental heat pain stimulation

Silver wire to TENS-device

Silver electrode for electric stimulation

Block-design of heat pain stimultion with overlay of fMRI signal (S=stimulation block 16 sec. and R=resting 32 sec.)

Pain threshold measurement

before intervention

Pain threshold Measurement

after intervention

• heat pain thresholds before and after TVNS/placebo

• changes of fMRI signal (neuronal activation) in

cerebral areas of „pain matrix“

Outcome measures

Cerebral pain-processing areas: „pain matrix“

Schweinhardt & Bushnell. J Clin Invest 2010;120:3788-97

„Pain matrix“

Schweinhardt & Bushnell. J Clin Invest 2010;120:3788-97

Experimental pain

• no differences in pain thresholds TVNS vs. placebo (N=20)

fMRI signal

• increased in left anterior insula, right posterior insula, right thalamus and anterior cingulate cortex (ACC) under placebo

• decreased ACC activation in contrast analysis TVNS vs. placebo

Results

Ascending pain pathway (red)

Decreased activation in pain matrix: anterior insular cortex (AIC), nucleus caudatus (NC), medial prefrontal cortex (mPFC)

and hypothalamus (HT) in contrast TVNS vs. placebo

Results of 8 volunteers responding to TVNS with pain threshold reduction

• Noxious heat stimulation elicited changes of fMRI signal in cerebral regions that are involved in the processing of pain

• TVNS led to decreased neuronal activation in the medial pain system

• anti-nociceptive effect of TVNS was associated with decreased activation of areas involved in emotional and cognitive pain regulation (anterior insular cortex, vmPFC and the caudate nucleus) as well as the hypothalamus as a brain region releasing stress hormones

Conclusions

Rene Laqua (radiologist)

Bianca Leutzow (anesthesiologist)

Martin Lotze (neurologist)

Thank you for your attention

Project team

University Medicine of Greifswald, Germany