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Nerve Growth Factor and Selected Cytokines in Women With and Without Vulvodynia

Reed, Barbara, D., MD, MSPH1; Plegue, Melissa, A., MA1; Sen, Ananda, PhD1,2; Haefner, Hope, K., MD3; Siddiqui, Javed, MS4; Remick, Daniel, G., MD5

Journal of Lower Genital Tract Disease: April 2018 - Volume 22 - Issue 2 - p 139–146
doi: 10.1097/LGT.0000000000000377
Original Research Articles: Vagina and Vulva

Objective The aim of the study was to assess the association between cytokines/neurokines after in vitro stimulation with Candida antigen or lipopolysaccharide (LPS) in blood samples among women with and without vulvodynia.

Materials and Methods Women with vulvodynia and asymptomatic controls at three offices at the University of Michigan were examined clinically and completed a comprehensive survey in this cross-sectional study. Cytokine/neurokine levels were determined on blood samples using established ELISA protocols. Analysis of 48 cases and 42 ethnically matched controls included descriptive statistics (median, minimal, and maximal levels of cytokines/neurokines), overall and in cases and controls. Because of left-censored measurements, interval censored survival analysis was used to assess the association between case/control status and pain characteristics with cytokine/neurokine levels.

Results Participants ranged in age from 19 to 60 years. Levels of IL1β, IL1-RA, TNFα, IL-6, and IL-8 increased substantially after LPS stimulation, whereas no response was seen on IFNγ or nerve growth factor (NGF). Each increased after Candida antigen stimulation, although responses to Candida antigen stimulation of IL1β, IL-6, and TNFα were less robust than after LPS. Only NGF was significantly increased in vulvodynia cases compared with controls (Exp β (95% CI) = 2.08 [1.08–3.98]) after 24-hour Candida antigen stimulation and persisted when controlled for age, use of oral contraceptives, or history of Candida vulvovaginitis. No association between cytokine/neurokine levels and pain characteristics was found.

Conclusions Compared with that of control women, whole blood from women with vulvodynia demonstrates an enhanced production of NGF, but not of a set of inflammation-related cytokines, in response to Candida antigen stimulation.

1University of Michigan, Department of Family Medicine, Ann Arbor, MI; 2University of Michigan, Department of Biostatistics, School of Public Health, Ann Arbor, MI; 3University of Michigan, Department of Obstetrics and Gynecology, Ann Arbor, MI; 4University of Michigan, Pathology MCTP, Ann Arbor, MI; and 5Boston University School of Medicine, Pathology & Laboratory, Boston, MA

Correspondence to: Barbara D. Reed, MD, MSPH, University of Michigan, Department of Family Medicine, 1018 Fuller Street, Ann Arbor, MI USA 48104-1213. E-mail:

The authors have declared they have no conflicts of interest.

Funding was received for this study from NICHD at the NIH (neuroimmunology/cytokine alterations in Vulvodynia HD40112).

The institutional review board status was approved by University of Michigan Medical IRB (HUM049893) on 4/18/17.

NIH had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Copyright © 2018 by the American Society for Colposcopy and Cervical Pathology