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Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.

ABSTRACT: Provoked vestibulodynia, the most common form of vulvodynia (unexplained pain of the vulva), is a prevalent, idiopathic pain disorder associated with a history of recurrent candidiasis (yeast infections). It is characterized by vulvar allodynia (painful hypersensitivity to touch) and hyperinnervation. We tested whether repeated, localized exposure of the vulva to a common fungal pathogen can lead to the development of chronic pain. A subset of female mice subjected to recurrent Candida albicans infection developed mechanical allodynia localized to the vulva. The mice with allodynia also exhibited hyperinnervation with peptidergic nociceptor and sympathetic fibers (as indicated by increased protein gene product 9.5, calcitonin gene-related peptide, and vesicular monoamine transporter 2 immunoreactivity in the vaginal epithelium). Long-lasting behavioral allodynia in a subset of mice was also observed after a single, extended Candida infection, as well as after repeated vulvar (but not hind paw) inflammation induced with zymosan, a mixture of fungal antigens. The hypersensitivity and hyperinnervation were both present at least 3 weeks after the resolution of infection and inflammation. Our data show that infection can cause persistent pain long after its resolution and that recurrent yeast infection replicates important features of human provoked vulvodynia in the mouse.

SUBMITTER: Farmer MA

PROVIDER: S-EPMC3243907 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.

Farmer Melissa A MA Taylor Anna M AM Bailey Andrea L AL Tuttle Alexander H AH MacIntyre Leigh C LC Milagrosa Zarah E ZE Crissman Halley P HP Bennett Gary J GJ Ribeiro-da-Silva Alfredo A Binik Yitzchak M YM Mogil Jeffrey S JS

Science translational medicine 20110901 101

Provoked vestibulodynia, the most common form of vulvodynia (unexplained pain of the vulva), is a prevalent, idiopathic pain disorder associated with a history of recurrent candidiasis (yeast infections). It is characterized by vulvar allodynia (painful hypersensitivity to touch) and hyperinnervation. We tested whether repeated, localized exposure of the vulva to a common fungal pathogen can lead to the development of chronic pain. A subset of female mice subjected to recurrent Candida albicans ...[more]

PMID: 21937756

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Project description:Patients with chronic overlapping pain conditions have decreased levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Consistent with clinical syndromes, we previously demonstrated that COMT inhibition in rodents produces persistent pain and heightened immune responses. Here, we sought to determine the efficacy of manual acupuncture in resolving persistent pain and neuroinflammation in the classic inbred C57BL/6 strain and the rapid-wound healing MRL/MpJ strain. Mice received subcutaneous osmotic minipumps to deliver the COMT inhibitor OR486 or vehicle for 13 days. On day 7 after pump implantation, acupuncture was performed at the Zusanli (ST36) point or a non-acupoint for 6 consecutive days. Behavioral responses to mechanical stimuli were measured throughout the experiment. Immunohistochemical analysis of spinal phosphorylated p38 mitogen-activated protein kinase, a marker of inflammation, and glial fibrillary acidic protein, a marker of astrogliosis, was performed on day 13. Results demonstrated that ST36, but not sham, acupuncture resolved mechanical hypersensitivity and reduced OR486-dependent increases in phosphorylated p38 and glial fibrillary acidic protein in both strains. The magnitude of the analgesic response was greater in MRL/MpJ mice. These findings indicate acupuncture as an effective treatment for persistent pain linked to abnormalities in catecholamine signaling and, furthermore, that analgesic efficacy may be influenced by genetic differences. PERSPECTIVE: Chronic overlapping pain conditions remain ineffectively managed by conventional pharmacotherapies. Here, we demonstrate that acupuncture alleviates persistent pain and neuroinflammation linked to heightened catecholaminergic tone. Mice with superior healing capacity exhibit greater analgesic efficacy. Findings indicate acupuncture as an effective treatment for chronic overlapping pain conditions and provide insight into treatment response variability.

Project description:IntroductionVulvodynia, vulvar pain syndrome, is defined as vulvar pain of at least a 3-month duration without a clear identifiable cause, which may have associated factor and the etiology and treatment of this challenging disease is still unclear. Dyspareunia is a relevant symptom of patients with vulvodynia. Vaginal microbiome has known an important role in local immune-inflammatory responses and it may be important pathogenic mechanism in vulvodynia.AimThe objective of this study was to investigate the association of vaginal microbiome and vulvodynia.MethodsWe analyzed the microbial compositions of the vestibule and vagina among women with clinically diagnosed vulvodynia (n = 22) and age-matched healthy controls (n = 22) without vulvodynia. The compositions of bacterial microbiomes were compared by pyrosequencing of the 16S rRNA.Main outcome measureVaginal microbiome alpha and beta diversity were assessed using the Shannon diversity index and Heat map. Linear discriminant analysis effect size was used to find out marker for vulvodynia.ResultsThere were no significant differences in the age, duration of marriage, history of gynecologic surgery, parity, and menopause status between cases and controls. A total of 1,661,934 high-quality pyrosequencing reads was obtained to evaluate bacterial diversity, and 50,246 unique sequences represented all phylotypes. The type and mean number of the genera were not different between cases and controls. However, the most predominant phyla of bacteria were significantly different between cases and controls. 3 phyla (Firmicutes, Actinobacteria, and Tenericutes) and 11 genera including Gardnerella, Ureaplasma, Achromobacter, Mycoplasma, and Bifidobacteria were significantly more prevalent in cases than in controls (P < .05). Linear discriminant analysis effect size analysis suggest the Bifidobacterium, Mycoplasma, and Fenollaria species can be potential markers for vulvodynia.ConclusionOur results suggest the differences in vaginal microbiome can be associated with the vulvodynia. Park SY, Lee ES, Lee SR, et al. Vaginal Microbiome Is Associated With Vulvodynia, Vulvar Pain Syndrome: A Case-Control Study. Sex Med 2021;9:100314.

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Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.

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Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia.

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