Miranda Varella Pereira et al. have conducted a systematic review of randomised placebo-controlled drug treatments of vulvodynia. And they conclude: evidence of a strong placebo effect. (1)
However, both treatments and placebo treatments in the five studies, that have met the criteria in the review, contain Sodium.
In two of them NaCl-solution is the placebo treatment (2)(3). In three of them various creams have been used as placebo treatment. (4)(5)(6). Creams always (/most often?) contain Sodium: Sodium Benzoate, Sodium Hydroxide, Sodium Dehydroacetate, Sodium Bicarbonate, Sodium Hyaluronate or others.
Therefore, the strong effect found in the five studies, could be ascribed to Sodium rather than to placebo effect.
Why Sodium has an effect on vulvodynia
Neuropathic pain is assoaciated with increased Calcium inside the nerve cells. This is the very downstream cause of the pain. (7)
The sodium-calcium exchanger NCX is a bidirectional transporter that catalyzes the electrogenic exchange of 3 Na(+) for 1 Ca(2+), depending on the electrochemical gradient of the substrate ions.(8)
Thus, the NCX will pump out Calcium from the nerve-cells, when it is presented with increased Sodium concentration at the exterior of the nerve cells. And the pain stops or is reduced.
References:
1) Miranda Varella Pereira G, Soriano Marcolino M, Silveira Nogueira Reis Z, Vale de Castro Monteiro M. A systematic review of drug treatment of vulvodynia: evidence of a strong placebo effect. BJOG. 2018 Sep;125(10):1216-1224. doi: 10.1111/1471-0528.15223. Epub 2018 Apr 15.
2) Petersen CD, Giraldi A, Lundvall L, Kristensen E. Botulinum toxin type A-a novel treatment for provoked vestibulodynia? Results from a randomized, placebo controlled, double blinded study. J Sex Med. 2009 Sep;6(9):2523-37. doi: 10.1111/j.1743-6109.2009.01378.x. Epub 2009 Jul 10.
3) Farajun Y, Zarfati D, Abramov L, Livoff A, Bornstein J.: Enoxaparin treatment for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2012 Sep;120(3):565-72. doi: 10.1097/AOG.0b013e3182657de6.
4) Bornstein J, Tuma R, Farajun Y, Azran A, Zarfati D. Topical nifedipine for the treatment of localized provoked vulvodynia: a placebo-controlled study. J Pain. 2010 Dec;11(12):1403-9. doi: 10.1016/j.jpain.2010.03.016. Epub 2010 May 26.
5) Donders GG and Bellen G. Cream with cutaneous fibroblast lysate for the treatment of provoked vestibulodynia: a double-blind randomized placebo-controlled crossover study. J Low Genit Tract Dis. 2012 Oct;16(4):427-36. doi: 10.1097/LGT.0b013e31825a2274.
6) Foster DC, Kotok MB, Huang LS, Watts A, Oakes D, Howard FM, Poleshuck EL, Stodgell CJ, Dworkin RH.: Oral desipramine and topical lidocaine for vulvodynia: a randomized controlled trial. Obstet Gynecol. 2010 Sep;116(3):583-93. doi: 10.1097/AOG.0b013e3181e9e0ab.
7) Fernyhough P and Calcutt NA: Abnormal calcium homeostasis in peripheral neuropathies. Cell Calcium. 2010 Feb; 47(2): 130–139. Published online 2009 Dec 24. doi: 10.1016/j.ceca.2009.11.008
8) Kuroda H, Sobhan U, Sato M, Tsumura M, Ichinohe T, Tazaki M, Shibukawa Y.: Sodium-calcium exchangers in rat trigeminal ganglion neurons. Mol Pain. 2013 Apr 29;9(1):22. doi: 10.1186/1744-8069-9-22.
Article Early outlined interdisciplinary theoretical explanation of ...
At the surface of Schwann cells could the described NCX-effect of Sodium prevent degradation of myelin and/or shift the Schwann cells into a myelinating mode.
Demyelination is caused by increased Calcium concentration in the cytosol of Schwann cells.
Gonzalez S, Berthelot J, Jiner J, Perrin-Tricaud C, Fernando R, Chrast R, Lenaers G, Tricaud N. Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies. J Clin Invest. 2016 Mar 1;126(3):1023-38. doi: 10.1172/JCI84505. Epub 2016 Feb 15.
Saline infusion is often used in the treatment of severe burn wounds, where the patients - like vulvodynia patients - have a strong burning sensation.
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