Anti-nociceptive properties of cardiopulmonary baroreceptors in patients with chronic back pain

Abstract

Introduction: Reduced pain perception following a persistent noxious stimulus during a study session (short-term habituation) is believed to be partially mediated by descending inhibitory mechanisms, although these mechanisms have not been fully elucidated. We examined the hypothesis that cardiopulmonary baroreceptor would significantly increase short-term habituation in chronic back pain (CBP) patients.

Methods: A short-term habituation protocol was utilized that involved 1-sec pulses (×10) at 105% heat pain threshold on the anterior forearm at 0.5 Hz. Cardiopulmonary baroreceptor unloading was performed via lower body negative pressure (LBNP) that reduces central venous pressure to elicit a reflex increase in sympathetic nerve activity.

Results: Short-term habituation was observed in young, healthy participants (n = 11), as indicated by a reduction in subjective pain ratings across the 10 repetitive heat pulses (-42% ± 29, P < 0.01, n = 11). Short-term habituation was also observed in CBP patients (-32% ± 30, P < 0.01, n = 12). Cardiopulmonary baroreceptor unloading via LBNP significantly reduced pain ratings across the 10 repetitive heat pulses in CBP patients compared with supine control (patient positioned in LBNP chamber but without a reduction in pressure) and upright sitting (chair), as indicated by a more negative area under the curve index (LBNP: -16.3 ± 4.1; Control: -14.4 ± 2.6; Upright sitting: -15.1 ± 4.1, P = 0.02). However, LBNP-mediated reductions in pain ratings were selective to CBP patients with more severe symptoms, i.e., neuropathic pain (LBNP: -14.7 ± 2.1; Control: -12.8 ± 1.4; Upright sitting: -12.1 ± 1.2, P = 0.04), whereas no effect of LBNP was observed in young, healthy participants (P = 0.83). In support, CBP patients with neuropathic pain exhibited significantly elevated mechanical pressure pain threshold during LBNP (P = 0.04).

Conclusions: Together, these findings demonstrate an association between cardiopulmonary baroreceptor unloading and a reduction in pain perception during repetitive noxious stimuli in CBP patients, particularly among CBP patients with greater pain severity.

Keywords: baroreflex; cardiopulmonary; chronic pain; descending inhibition; sympathetic nerve activity (SNA).

Figure 1

Short-term habituation protocol. (A) Ten repetitive heat pulses were administered at an intensity of 105% of each participant's previously determined heat pain threshold. (B) The ten repetitive heat pulses were divided into 9 subintervals using a right end point approximation for quantification of area under the curve (AUC). The initial AUC is represented by the first interval (average pain ratings of first and second heat pulses) and is divided by the total AUC to determine short-term habituation (AUC index). Example data provided in panels (B,C) are average data for patients with CBP (n = 12).

Figure 2

Reliability analysis of short-term habituation in young, healthy participants (n = 11). (A) Subjective pain ratings following ten repeated thermal stimuli at 105% threshold in the upright sitting position on separate visits within 1 week. Each participant was blinded to the intensity and was instructed that each trial would be somewhat less, more, or the same as their threshold intensity in a randomized fashion. Differences between time points and conditions were tested using a two-way repeated measures ANOVA. (B–D) Short-term habituation in each participant at visit 1 and visit 2 as determined by the area under the curve method (AUC index), last-first method, and the slope method. (E) Intraclass correlation ± 95% confidence intervals to test reliability of short-term habituation between visit 1 and visit 2 while using the AUC index method, last-first method, and the slope method.

Figure 3

Short-term habituation during baroreceptor loading and unloading in young, healthy participants (n = 7). (A) Subjective pain ratings of ten repeated thermal stimuli in the upright sitting condition, supine position (control, 0 mmHg), and supine position with lower body negative pressure (LBNP) of −10 mmHg, and (B) short-term habituation during baroreceptor loading and unloading determined using the area under the curve method (AUC index). Potential differences between time points and conditions were tested using a two-way repeated measures ANOVA (A) and differences in AUC index between conditions were tested using a one-way repeated measures ANOVA (B).

Figure 4

Short-term habituation during baroreceptor loading and unloading in patients with chronic back pain (CBP, n = 12). Subjective pain ratings of ten repeated thermal stimuli in the upright sitting condition, supine position (control, 0 mmHg), and supine position with lower body negative pressure (LBNP) of −10 mmHg in all CBP patients (A) and segregated into the CBP group with nociceptive pain components (B) (n = 6) and the CBP group with neuropathic pain components (C) (n = 6). Differences between time points and conditions were tested using a two-way repeated measures ANOVA. Short-term habituation during baroreceptor loading and unloading was determined using the area under the curve method (AUC index) in all CBP patients (D) and segregated into the CBP group with nociceptive pain components (E) and the CBP group with neuropathic pain components (F) Potential differences in AUC index between conditions were tested using a one-way repeated measures ANOVA. * P < 0.05.

Figure 5

Mechanical pressure pain threshold during baroreceptor loading and unloading. Pressure pain threshold was tested in the upright sitting condition, supine position (control, 0 mmHg), and supine position with lower body negative pressure (LBNP) of −10 mmHg in young, healthy participants (A) (n = 8), in all CBP patients (B) (n = 12) and segregated into the CBP group with nociceptive pain components (C) (n = 6) and the CBP group with neuropathic pain components (D) (n = 6). The outlier data point in panel A is equal to 578 kgf and results were not different if removed. Potential differences between conditions were tested using a one-way repeated measures ANOVA. * P < 0.05.

Figure 6

Cardiovascular responses to lower body negative pressure (LBNP). Total peripheral resistance (A), cardiac output (B), and mean arterial pressure (C) during the initial onset of LBNP, during steady state LBNP when sensory testing was performed (shaded region), and during recovery when chamber pressure reaches baseline (0 mmHg) in young, healthy participants (left panels) (n = 7) and patients with chronic back pain (CBP, right panels) (n = 12). Solid lines represent the control condition where no vacuum seal was present and chamber pressure remained at 0 mmHg, and dotted lines represent LBNP with chamber pressure of −10 mmHg (conditions were randomized). Because data were not always normally distributed, differences between timepoints and conditions were tested using Generalized Estimating Equations and pairwise comparisons were performed when significant interactions were detected. * P < 0.05 vs. control condition (0 mmHg).