Evoked pain analgesia in chronic pelvic pain patients using respiratory-gated auricular vagal afferent nerve stimulation

Abstract

Objective: Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS.

Design: Counterbalanced, crossover study.

Patients: Patients with chronic pelvic pain (CPP) due to endometriosis in a specialty pain clinic. INTERVENTIONS/OUTCOMES: We evaluated evoked pain analgesia for respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) compared with nonvagal auricular stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least 1 week apart. Outcome measures included deep-tissue pain intensity, temporal summation of pain, and anxiety ratings, which were assessed at baseline, during active stimulation, immediately following stimulation, and 15 minutes after stimulus cessation.

Results: RAVANS demonstrated a trend for reduced evoked pain intensity and temporal summation of mechanical pain, and significantly reduced anxiety in N = 15 CPP patients, compared with NVAS, with moderate to large effect sizes (η(2) > 0.2).

Conclusion: Chronic pain disorders such as CPP are in great need of effective, nonpharmacological options for treatment. RAVANS produced promising antinociceptive effects for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.

Wiley Periodicals, Inc.

Figures

Figure 1. Schematic of Integrative Innervation of the NTS

The nucleus tractus solitarius (NTS) in the medulla integrates afferent inputs from the cervical vagus (X, e.g. aortic arch baroreceptors, lungs), glossopharyngeal nerve (IX, e.g. carotid baroreceptors), and auricular branch of the vagus (ABV). NTS input to higher brain regions processing different aspects of pain is thought to underlie the anti-nociceptive effects of vagus nerve stimulation (VNS). N.b. SpV = trigeminal nucleus, PB = parabrachial nucleus, LC = locus ceruleus, PAG = periaqueductal gray, hyp = hypothalamus, amyg = amygdala, thal = thalamus, ins = insula, ACC = anterior cingulate cortex, PFC = prefrontal cortex, S1 = primary somatosensory cortex.

Figure 2. Schematic of the RAVANS procedure

(A) Subjects were outfitted with a thoracic belt to measure respiratory excursions. This signal was transduced and fed into a laptop controller, allowing for left t-VNS stimulation to occur only during the expiratory phase of respiration. (B) Auricular anatomy includes important regions including the cymba and cavum conchae, as well as the antihelix. (C) Auricular electrodes were placed within the cymba concha and antihelix, the two regions found to be most consistently innervated by the ABV nerve [32].

Figure 3. Response of deep pain intensity to RAVANS vs. NVAS

Evoked deep pain intensity was reduced (p

Figure 4. Response of temporal summation of pain to RAVANS vs. NVAS

Temporal summation of pain was reduced (p=0.05) during RAVANS stimulation, while a trend (p=0.07) was found for reduction immediately following RAVANS stimulation, and comparing RAVANS and NVAS during stimulation. N.b. * = p

Figure 5. Response of anxiety ratings to RAVANS vs. NVAS

Anxiety was reduced (p’s 0.3) at any time points in the NVAS session. Reductions in anxiety were significantly larger in the RAVANS than the NVAS session at each time point (p’s