Altered central sensitization in subgroups of women with vulvodynia

Abstract

Objective: To investigate the clinical correlates of central nervous system alterations among women with vulvodynia. Altered central sensitization has been linked to dysfunction in central nervous system-inhibitory pathways (e.g., γ-aminobutyric acidergic), and metrics of sensory adaptation, a centrally mediated process that is sensitive to this dysfunction, could potentially be used to identify women at risk of treatment failure using conventional approaches.

Methods: Twelve women with vulvodynia and 20 age-matched controls participated in this study, which was conducted by sensory testing of the right hand's index and middle fingers. The following sensory precepts were assessed: (1) vibrotactile detection threshold; (2) amplitude discrimination capacity (defined as the ability to detect differences in intensity of simultaneously delivered stimuli to 2 fingers); and (3) a metric of adaptation (determined by the impact that applying conditioning stimuli have on amplitude discriminative capacity).

Results: Participants did not differ on key demographic variables, vibrotactile detection threshold, and amplitude discrimination capacity. However, we found significant differences from controls in adaptation metrics in 1 subgroup of vulvodynia patients. Compared with healthy controls and women with a shorter history of pain [n=5; duration (y) = 3.4 ± 1.3], those with a longer history [n=7; duration (y) = 9.3 ± 1.4)] were found to be less likely to have adaptation metrics similar to control values.

Discussion: Chronic pain is thought to lead to altered central sensitization, and adaptation is a centrally mediated process that is sensitive to this condition. This report suggests that similar alterations exist in a subgroup of vulvodynia patients.

Fig. 1

Images of the multi-site vibrotactile stimulator. Stimulators are positioned by rotating each of the 4 independently positioned drums to maximize contact between fingers and the stimulator tips. During an experimental session, the subject was seated comfortably in a chair with the right arm resting on the arm rest attached to the head unit of the stimulator. Index and middle finger were positioned for D2 and D3 stimulation.

Fig. 2

Schematics of the protocols used in this study.

1. Vibrotactile detection threshold protocols. Left panel: 2AFC tracking protocol: In each trial, a 25 Hz vibrotactle test stimulus was delivered to either D2 or D3 for 0.5 sec, followed by a subject response interval (RI). Subject was prompted to select the skin site that perceived the stimulus. A 5 sec inter-trial interval (ITI) intervened between stimulus response and onset of the next trial. Right panel: Dynamic tracking protocol: A delay period (n sec = 0, 1.5, 2 or 3 sec) without any stimulation was applied. After the initial delay, a 25 Hz vibrotactile stimulus was delivered to either D2 or D3. The amplitude of the stimulus was initiated from zero and increased in steps of 2 μm/sec. The stimulation was terminated with subject response to the perceived stimulus.

2. Amplitude discrimination protocols. Left panel: Amplitude discrimination at baseline: Two 25 Hz vibrotactile stimuli, the standard (S) and test (T), were delivered simultaneously for 0.5 sec. Subject was asked to choose the stimulus that was perceptually larger. Right panel: Amplitude discrimination task with pre-exposure to conditioning stimulation. A 25 Hz conditioning stimulus was delivered 1 sec prior to the presentation of the test and standard stimuli.

3. Dynamic tracking with adaptation protocol: Two identical 25 Hz vibrotactile stimuli were delivered simultaneously for a fixed interval (n sec = 0, 1.5, 2, or 3 sec). After the initial constant stimulus period, the amplitude of the two stimuli were dynamically increased/decreased, in steps of 25 μm/sec. Stimulation was terminated with subject response to the location at which the most intense stimulus was delivered.

Fig. 3

Summary of group-averaged vibrotactile detection thresholds obtained with two different methods on two sub-groups of patients with vulvodynia and controls. Static threshold: No significant difference were observed on the static thresholds between any patients group and controls (Group A vs. controls: p = 0.35; Group B vs. controls: p = 0.51). Dynamic threshold: The group-averaged dynamic thresholds of patients with vulvodynia did not significantly differ from that of controls, while data from patients in Group B show a trend for lower dynamic threshold than controls.

Fig. 4

Comparison of weber’s fraction obtained with amplitude discrimination protocols (without/with pre-exposure to a single-site conditioning stimulus). In the absence of conditioning stimulus, no significant difference was observed between the performance of controls and sub-groups of vulvodynia patients. Pre-exposure to a single-site conditioning stimulation (1 sec in duration) caused a significant degradation of performance in the controls (p < 0.01) and the patients in Group B (p = 0.017). Contrary to controls and Group B, patients in Group A performed equally well under both adapted and un-adapted conditions. Under the condition with adaptation, the group-averaged performance is significantly different between controls and Group A (p = 0.036).

Fig. 5

Weber’s fraction obtained under the condition with adaptation was normalized on a subject-by-subject basis to the un-adapted condition. The 1 sec conditioning stimulus significantly impaired the subjects’ amplitude discrimination capacity by nearly 30% for both the controls and the patients in Group B, while there were much lesser effects (3%) of adaptation observed in the patients in Group A.

Fig. 6

Comparison of the group-averaged performance with dual-site adaptation at the four different durations of dual-site conditioning stimulation (0, 1.5, 2 and 3 sec) for the controls and two sub-groups of patients with vulvodynia. Increasing the duration of the conditioning stimuli led to an improvement of performance (i.e., reduced DL). As the data obtained from patients in Group B deviated very little from that of controls, DLs obtained from patients in Group A were significantly higher compared to controls and showed only little effect with adaptation.