New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells

Journal of Pain Research, Oct 2016

New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells J M Keppel Hesselink,1 D J Kopsky,2 N Sajben3 1Institute for Neuropathic Pain, Bosch en Duin, 2Institute for Neuropathic Pain, Amsterdam, The Netherlands; 3Scripps Memorial Hospital La Jolla, La Jolla, CA, USA Abstract: Topical treatments of localized neuropathic pain syndromes in general are mostly neglected, mainly due to the fact that most pain physicians expect that a topical formulation needs to result in a transdermal delivery of the active compounds. On the basis of the practical experience, this study brings forth a new, somewhat neglected element of the vulvodynia pathogenesis: the cross talk between the nerve endings of nociceptors, the adjacent immunocompetent cells, and vaginal epithelial cells. Insight into this cross talk during a pathogenic condition supports the treatment of vulvodynia with topical (compounded) creams. Vulvodynia was successfully treated with an analgesic cream consisting of baclofen 5% together with the autacoid palmitoylethanolamide 1%, an endogenous anti-inflammatory compound. In this review, data is presented to substantiate the rationale behind developing and prescribing topical products for localized pain states such as vulvodynia. Most chronic inflammatory disorders are based on a network pathogenesis, and monotherapeutic inroads into the treatment of such disorders are obsolete. Keywords: vulva, cream, autacoid, mast cell, pain, analgesia, pathogenesis, baclofen, palmitoylethanolamide

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New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells

Journal of Pain Research New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells J M Keppel Hesselink 2 D J Kopsky 1 N Sajben 0 0 Scripps Memorial Hospital La Jolla , La Jolla, CA , USA 1 Institute for Neuropathic Pain , Amsterdam , The Netherlands 2 Institute for Neuropathic Pain , Bosch en Duin Topical treatments of localized neuropathic pain syndromes in general are mostly neglected, mainly due to the fact that most pain physicians expect that a topical formulation needs to result in a transdermal delivery of the active compounds. On the basis of the practical experience, this study brings forth a new, somewhat neglected element of the vulvodynia pathogenesis: the cross talk between the nerve endings of nociceptors, the adjacent immunocompetent cells, and vaginal epithelial cells. Insight into this cross talk during a pathogenic condition supports the treatment of vulvodynia with topical (compounded) creams. Vulvodynia was successfully treated with an analgesic cream consisting of baclofen 5% together with the autacoid palmitoylethanolamide 1%, an endogenous anti-inflammatory compound. In this review, data is presented to substantiate the rationale behind developing and prescribing topical products for localized pain states such as vulvodynia. Most chronic inflammatory disorders are based on a network pathogenesis, and monotherapeutic inroads into the treatment of such disorders are obsolete. - Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: http://youtu.be/R4pJICQIeA4 Introduction Vulvodynia is frequently present in women between 18 and 60 years, with a prevalence between 4% and 16%, though it may be underestimated due to underreporting bias. Although the International Society for the Study of Vulvovaginal Disease defines vulvodynia as “vulvar pain occurring in the absence of an underlying recognizable disease”, we think its pathogenesis can be defined within certain boundaries in such a way that rational therapy can emerge.1 Vulvodynia is differentiated into localized and generalized subtypes, although both these are probably extreme variations of one syndrome.1 Localized provoked vestibulodynia or vulvodynia (LPV) is a clinical diagnosis and is defined by a characteristic pattern of mechanical allodynia localized to the vulvar vestibule upon stimulation.2 However, the classification of this disorder is still very much in flux. In 2015, new nomenclature was developed at a vulvar pain and vulvodynia consensus conference supported by International Society for the Study of Vulvovaginal Disease, the International Society for the Study of Women’s Sexual Health, and the International Pelvic Pain Society, and this needs further consolidation. Most LPV cases can be regarded as a manifestation of a (localized) neuropathic pain disorder because vulvodynia is described by patients as burning, stinging, irritation, 8 1 0 2 l u J 3 1 n o 7 0 2 . 6 4 . 9 5 . 7 3 y b / m o c . s s rvepe l.yno and/or rawness, and thus has comparable pain characteristics as postherpetic neuralgia and complex regional pain syndrome.3 In this article, we will not differentiate between the local and the generalized variety of vulvodynia, and we will use the term vulvodynia to cover all primary and secondary or generalized varieties. The therapy of vulvodynia is still in its infancy, and many treatment options have been extrapolated from other fields, such neuropathic pain or infectious disease. Furthermore, most treatment recommendations are based on personal opinions and are based neither on an extensive understanding of the pathogenesis of this disorder nor on the results of robust methodologically sound clinical trials. One of the key players in the pathogenesis not generally recognized might be the epithelial cell, a cell in close contact with nerve endings of nociceptors in the vaginal area in such a way that cross talk occurs between these components and other components such as immune competent cells (eg, mast cells). A new putative treatment option for vulvodynia will be ./dowww lsueano doirsicnucsosemdbbiansaetidoonnwthitehaapuptaliccoaitdiosn,soufcthopaiscpaallamnaitlogyelseitahaalnoonle/ ttsp rspe amide, the latter administered either locally or systemically. : ohm roF We feel that new therapeutic options based on the combinafrd tion of specifically selected active compounds influencing the dea pathogenetic cross talk between epithelial cells, upregulated lnow vulvar nociceptors, as well as the immunocompetent cells in do this area, should be taken into consideration. rcha On the basis of our past experience in prescribing topisee cal analgesic creams containing baclofen or amitriptyline, ianR together with the autacoid palmitoylethanolamide, to women foP suffering from vulvodynia, we have identified some important lran facts. The latter compound (palmit (...truncated)


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J M Keppel Hesselink, D J Kopsky, N Sajben. New topical treatment of vulvodynia based on the pathogenetic role of cross talk between nociceptors, immunocompetent cells, and epithelial cells, Journal of Pain Research, 2016, pp. 757-762, DOI: 10.2147/JPR.S115407