Can Wound Exudate from Venous Leg Ulcers Measure Wound Pain Status?: A Pilot Study

<div><p>We investigated the associations between the self-evaluated pain status and two pain biomarker candidates, nerve growth factor and S100A8/A9, in exudate from venous leg ulcer to finally develop an objective pain evaluation method. Patients with venous leg ulcer participated in this cross-sectional observational study conducted between April and October 2014 at two medical facilities. During routine wound care, each participant self-evaluated their pain status at each examination using the 10-point numerical rating scale (present pain intensity) and the short-form McGill Pain Questionnaire 2 (continuous pain, intermittent pain, neuropathic pain, affective descriptors, and total score). Venous leg ulcer exudate sample was collected after wound cleansing. The nerve growth factor and S100A8/A9 concentrations in the venous leg ulcer exudate were measured by enzyme-linked immunosorbent assay and standardized according to the wound area. The association between each pain status and the two standardized protein concentrations was evaluated using Spearman’s correlation coefficient. In 30 sample collected from 13 participants, the standardized nerve growth factor concentration was negatively correlated with continuous pain (<i>ρ</i> = -0.47, <i>P</i> = 0.01), intermittent pain (<i>ρ</i> = -0.48, <i>P</i> = 0.01), neuropathic pain (<i>ρ</i> = -0.51, <i>P</i> = 0.01), and total score (<i>ρ</i> = -0.46, <i>P</i> = 0.01). The standardized S100A8/A9 concentration was positively correlated with present pain intensity (<i>ρ</i> = 0.46, <i>P</i> = 0.03) and continuous pain (<i>ρ</i> = 0.48, <i>P</i> = 0.03). Thus, these two proteins may be useful for objective evaluation of wound pain in venous leg ulcer patients.</p></div

Changes in continuous pain intensity and standardized protein concentrations in ID “G”.

<p>The protein concentrations were standardized according to the wound area, and then the standardized S100A8/A9 concentration was multiplied 10-fold for clarity. The horizontal axis indicates the duration in weeks from the first examination. Numbers of NGF data were 9, and of S100A8/A9 were 7 in spite of 10 time points because NGF was not detected in one sample from observation number 8, and S100A8/A9 was not detected in samples from observation numbers 10, 12, and 16. NGF = nerve growth factor.</p

Participant characteristics (n = 13).

<p>Participant characteristics (n = 13).</p

Associations between pain intensity and standardized NGF and S100A8/A9 concentrations.

<p>Associations between pain intensity and standardized NGF and S100A8/A9 concentrations.</p

Self-evaluated pain intensity (N = 30).

<p>Self-evaluated pain intensity (N = 30).</p

Wound and pain characteristics during each examination.

<p>Wound and pain characteristics during each examination.</p