Cardiac-Gated Neuromodulation Increased Baroreflex Sensitivity and Reduced Pain Sensitivity in Female Fibromyalgia Patients

Abstract

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether administration of noxious and non-noxious electrical stimuli synchronized with the cardiac cycle resets BRS, reestablishing pain inhibition. A total of 30 pain-free normotensives controls (NC) and 32 normotensives fibromyalgia (FM) patients received two, ≈8 min-epochs of cardiac-gated, peripheral electrical stimuli. Non-painful and painful electrical stimuli were synchronized to the cardiac cycle as the neuromodulation experimental protocol (EP) with two control conditions (CC1, CC2). BRS, heart-rate-variability (HRV), pain threshold and tolerance, and clinical pain intensity were assessed. Reduced BRS in FM at baseline increased by 41% during two, ≈8 min-epochs of stimulation. Thresholds in FM increased significantly during the experimental protocol (all Ps < 0.001) as did HRV. FM levels of clinical pain significantly decreased by 35.52% during the experimental protocol but not during control stimulations (p < 0.001). Baroreceptor training may reduce FM pain by BRS-mediated effects on intrinsic pain regulatory systems and autonomic responses.

Keywords: baroreflex sensitivity; dmNTS; fibromyalgia; neuromodulation; pain inhibition.

Figure 1

NTS reflex arcs.

Figure 2

Design of the experiment with the EP, CC1 and CC2 protocols. CC1: control condition 1 protocol. CC2: control condition 2 protocol. EP: experimental protocol. PT: pain threshold. ST: sensory threshold. TT: tolerance threshold.

Figure 3

Changes in pain thresholds and tolerance (in %) in response to 2, ≈8 min EP, CC1, and CC2 protocols. * p < 0.05, ** p < 0.01, *** p < 0.001. CC1: control condition 1. CC2: control condition 2. EP: experimental protocol. FM: fibromyalgia patients. NC: normotensive controls.

Figure 4

Changes in clinical pain intensity in response to 2, ≈8 min EP, CC1 and CC2 protocols assessed by visual analogue scale (0–100). * p < 0.05, *** p < 0.001 comparing pre- vs. post-responses. CC1: control condition 1. CC2: control condition 2. EP: experimental protocol.

Figure 5

Mean BRS values in EP, CC1, and CC2 protocols, ** p < 0.01 comparing baseline to epoch 1st and to epoch 2nd in FM and NC. Base: baseline. BRS: baroreflex sensitivity. CC1: control condition 1. CC2: control condition 2. EP: experimental protocol. FM: fibromyalgia patients. NC: normotensive controls.

Figure 6

Vagal activity in baseline, epoch 1 and epoch 2 of EP protocol measured by HF in FM and NC. ** p < 0.01 comparing baseline to epoch 1 and to epoch 2. FM: fibromyalgia patients. HF: high frequency. NC: normotensive controls.