Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation

J Low Genit Tract Dis. 2013 Apr;17(2):111-6. doi: 10.1097/LGT.0b013e3182652316.


Objective: The study aimed to assess the effect of palmitoylethanolamide + transpolydatin combination in patients with vestibulodynia undergoing transcutaneous electrical nerve stimulation (TENS) therapy and to confirm the effectiveness of TENS also in a domiciliary protocol. The study is based on the premise that palmitoylethanolamide + transpolydatin combination may contribute to a down-regulation of mast cell hyperactivity, which is believed to be responsible for the proliferation and sprouting of vestibular pain fibers and the associated hyperalgesia and allodynia.

Materials and methods: Twenty women with vestibulodynia were randomly assigned to receive oral palmitoylethanolamide (PEA) 400 mg and transpolydatin 40 mg or placebo, twice daily for 60 days. All patients underwent TENS therapy in a self-administered home protocol. Visual analogue scale (VAS), Marinoff score for dyspareunia, and current perception threshold obtained from the vulvar vestibule were assessed at baseline and at the end of treatment.

Results: The patients received a mean of 26.7 TENS sessions. All scores in the 2 groups improved significantly, although the level of improvement was similar between the groups (VAS, p < .57; dyspareunia, p < .38). Nevertheless, the analysis of regression of symptoms related to the duration of disease revealed the therapy to be more effective when PEA + transpolydatin is included in cases with more recent disease onset, as compared with the placebo group (PEA: VAS, p < .01; dyspareunia, p < .01) (placebo: VAS, p = nonsignificant; dyspareunia, p = nonsignificant).

Conclusions: This study confirms that TENS is of significant benefit in the management of vestibulodynia, also in a home environment. PEA + transpolydatin can be a value-added treatment adjunct when the onset of vestibulodynia is more recent or when the disease relapses.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Amides
  • Analgesics / administration & dosage*
  • Drug Synergism*
  • Endocannabinoids / administration & dosage*
  • Ethanolamines / administration & dosage*
  • Female
  • Glucosides / administration & dosage*
  • Humans
  • Middle Aged
  • Palmitic Acids / administration & dosage*
  • Placebos / administration & dosage
  • Stilbenes / administration & dosage*
  • Transcutaneous Electric Nerve Stimulation / methods*
  • Treatment Outcome
  • Vulvodynia / drug therapy*
  • Young Adult


  • Amides
  • Analgesics
  • Endocannabinoids
  • Ethanolamines
  • Glucosides
  • Palmitic Acids
  • Placebos
  • Stilbenes
  • palmidrol
  • polydatin