Respiratory-Gated Vagal Nerve Stimulation for Chronic Pain
Condition: Chronic Pain
MeSH terms: Chronic Pain
Study type: Interventional

Summary: 
      Vagus Nerve Stimulation (VNS) is a validated and FDA-approved therapy that has improved the
      lives of many individuals with epilepsy and depression and has shown promise for treating
      chronic pain. However, there is moderate morbidity associated with the surgical procedure and
      maintenance of VNS. The study team has developed a novel, non-invasive procedure based on the
      neurobiology of VNS treatment which is termed Respiratory-gated Auricular Vagal Afferent
      Nerve Stimulation (RAVANS). The investigators hope to maximize efficacy and better understand
      applicability of RAVANS by applying this to chronic pain patients with a range of psychiatric
      and psychological comorbidity. This high-distress subpopulation of chronic pain patients has
      been notoriously difficult to treat and is in need of new, innovative therapies. The
      investigators propose applying electrical stimulation of the somatosensory vagal afferent
      receptors in the ear using transcutaneous-VNS (t-VNS) during the exhalation phase of
      breathing in order to augment the clinical efficacy of t-VNS.

      This proposal includes a single blinded, controlled design for testing the impact of RAVANS
      therapy on pain and mood fro chronic pain. Patients will complete 2 in-person visits, one
      with RAVANS therapy and one with non-RAVANS stimulation. During each session, participants
      will complete questionnaires, quantitative sensory testing (QST), and receive either real or
      sham RAVANS stimulation.
    

Detailed description: 
      Testing will occur over the course of 2 2-3 hour study visits. After completing consent
      forms, participants will complete questionnaires and undergo baseline Quantitative Sensory
      Testing (QST). After baseline sensory testing and completion of measures, participants will
      complete a 30-minute rest period during which time they are instructed to relax and regulate
      their breathing. After the rest, they will receive a 30-minute RAVANS or non-RAVANS
      stimulation. Following the RAVANS stimulation, participants will again undergo QST testing.
      Throughout the session, subjects will rate pain and mood using numeric rating scales and
      physiological monitoring will occur as described below.

      RAVANS stimulation Electrodes will be placed in the auricle of the left ear. Electrical
      stimulation to these electrodes will be provided by a current-constant stimulator (Urostim,
      Schwa-Medico). Stimulation will be gated, with 1-second delay, after peak inhalation (i.e.
      during exhalation). Respiratory gating for stimulation will require real-time evaluation of
      the respiratory cycle. The study will use a belt system constructed in-house, and similar to
      the system used in several previous studies. A pneumatic belt will be placed around the
      subject's lower thorax. Once electrodes are set up, subjects will be asked to rate
      stimulation intensity on a NRS of 0 to 10 (0: no sensation, 10: pain detection threshold).
      Current intensity will be set to achieve moderate to strong (but not painful) sensation, and
      this current intensity will be used on subsequent stimulation runs.

      Non-RAVANS stimulation For sessions randomized to sham stimulation, the electrodes in the ear
      will remain as described above, but the leads will be disconnected from the stimulator.
      Subjects will be instructed that for this session they may or may not feel pulsing in their
      ear, and that the goal is to ensure that the stimulus was not painful.

      Physiological Monitoring In addition to respiration, which by necessity will be monitored
      with the pneumatic belt as part of the RAVANS procedure, the investigators will also collect
      ECG data. The ECG signal will also be acquired by a laptop device system, temporally locked
      to the respiratory signal. The ECG can be used to quantify heart rate and heart rate
      variability.

      Sensory Tests to be Completed at Baseline and After Experimental Condition:

      These procedures are similar to those used in ongoing QST studies (e.g., IRB protocols
      2009P001020, 2010P000978, 2015P002373).

      Mechanical pain: Responses to punctate mechanical stimuli will be measured using a standard
      set of weighted probes that provide estimates of pain threshold and mechanical temporal
      summation. Series of 10 stimuli (with 1-second inter-stimulus intervals) will be used to
      assess the temporal summation of pain that occurs with rapid administration of identical
      stimuli. A Somedic pressure algometer will be utilized to assess responses to pressure
      stimulation at several anatomical sites. Pain pressure thresholds (PPT) will be determined
      twice at the knee, trapezius, and thumb. Mechanical pressure will be applied using a 0.5-cm2
      probe covered with 1mm polypropylene pressure-transducing material; pressure is increased at
      a steady rate of 30 kPA/s until the subject indicates that the pressure has become painful.
      Finally, the study will use cuff algometry to assess responses to sustained mechanical
      pressure. A Hokanson rapid cuff inflator will be used to inflate a standard blood pressure
      cuff around the gastrocnemius muscle to a moderately painful level for up to 2 minutes.
      Participants will indicate when the pressure first becomes painful (i.e., pain threshold) and
      will provide pain ratings every 30 seconds. As with each of these psychophysical testing
      procedures, participants are informed that they may terminate the procedure at any time.
    

Intervention name(s): RAVANS
Intervention type(s): Device
Intervention description(s): Electrical stimulation of somatosensory vagal afferent receptors in the ear modulated by respiration.
Other intervention name(s): Respiratory-gated Auricular Vagal Afferent Nerve Stimulation
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: vagus nerve stimulation