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 anti-nociceptive effects, and recent non-invasive approaches; termed transcutaneous-VNS, or 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 Non-Vagal Auricular Stimulation (NVAS). RAVANS and NVAS were evaluated in separate sessions spaced at least one 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 to NVAS, with moderate to large effect sizes (eta2>0.2). Conclusion Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS produced promising anti-nociceptive effects for 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.

Non-invasive Access to the Vagus Nerve Central Projections via Electrical Stimulation of the External Ear: fMRI Evidence in Humans

“…While the present study was conducted on a healthy population and focused on elucidating the central projections of the ABVN there are reports of cognitive and behavioral effects of t-VNS and VNS, i.e., antinociception [7,29,43,58], anti-depression [22,41,53], and anti-convulsion [10,55,57]. The mechanisms underlying these effects are unclear.…”

“…In addition to the above neuroanatomical and brain imaging studies, there is evidence that t-VNS produces cognitive and behavioral effects that are also produced by VNS [7,10,22,29,41,43,53,55,57,58]. Based on conventional neuroanatomy, VNS would be expected to activate the vagal projections beginning centrally at the NTS; therefore, it is likely that t-VNS, via the ABVN, would also activate the NTS.…”

The hippocampus and TNF: Common links between chronic pain and depression

“…Whereas electroconvulsive therapy and vagal nerve stimulation are FDA-approved for the treatment of refractory depression Rush et al, 2005), these procedures also reduce pain in patients suffering from chronic pain induced by migraines and cluster headaches (Hord et al, 2003;Multon and Schoenen, 2005) and from chronic pelvic pain (Napadow et al, 2012). Several case reports demonstrate electroconvulsive therapy effectiveness in the treatment of comorbid chronic pain and depression (Suzuki et al, 2009;Wasan et al, 2004).…”

Non-invasive Vagus Nerve Stimulation in Healthy Humans Reduces Sympathetic Nerve Activity

“…These studies also reported that the improvement in angina symptoms persisted after the cessation of tVNS treatment for up to 3 weeks. Recently, tVNS using surface electrodes has been investigated as a possible analgesic (15,36) and has also been trialled as an alternative to invasive cervical VNS in patients with refractory epilepsy (14). These studies also monitored heart rate and blood pressure and reported no significant changes.…”

“…This stimulation can be performed transcutaneously by applying surface electrodes or acupuncture needles to the external ear (tVNS). Such tVNS has been trialled in patients with coronary artery disease (12,13), epilepsy (14) and chronic pain (15), however, the outcomes investigated are varied and mostly subjective. In addition, the stimulation parameters used differ widely, therefore, little is known about the optimal parameters for tVNS.…”