“SIN Syndrome” – A new mechanism for mesh inguinodynia R. Bendavid & V. Iakovlev Shouldice Hospotal, Richmond Hill, Canada Department of Pathology, St. Michael’s Hospital and Keenan research Centre of the Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Canada

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Background Surgical polypropylene meshes were introduced in late 1950’s Applications spread to non-hernia sites, presently annual worldwide use is several million devices Depending on site 2-8% are excised for complications (infection, pain, hernia recurrence, mucosal erosion, transmigration) – abundant material to study Many (likely >50%) of explanted meshes are not examined microscopically. * Even if they are pathologists are not aware of mesh related issues. Paradoxically, with the availability of abundant material from humans most conclusions are based on animal studies * Smith T.M., Smith S.C., Delancey J.O., Fenner D.E., Schimpf M.O., Roh M.H., Morgan D.M., “Pathologic evaluation of explanted vaginal mesh: interdisciplinary experience from a referral center,” Female Pelvic Med Reconstr Surg., vol. 19,no. 4, pp. 238-41, Jul. 2013.

Appearance of mesh in histological sections Mesh is encased in scar tissue, on the outside and within the pores and folds. Bendavid, R. , Lou, W. , Koch, A., Iakovlev, V. Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain. International Journal of Clinical Medicine, 2014, 5:799-810

reinnervation and neoinnervation Is scar within mesh innervated? Nerve structures of any caliber (nerves, nerve twigs, individual nerve fibers) can grow into the mesh in the process of reinnervation and neoinnervation S100 stain, nerve branches are stained brown Cross-sectioned mesh filaments are filled yellow in the pictures

Does mesh affect nerve growth into the scar? 3 groups of samples: 10 virgin tissue at primary repair 10 scar sample at revision after non-mesh repair 10 biopsied mesh samples at surgery for recurrence Bendavid, R. , Lou, W. , Koch, A., Iakovlev, V. Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain. International Journal of Clinical Medicine, 2014, 5:799-810

Significance of mesh and nerves interaction Innervated tissue is exposed to all regular pain mechanisms: Direct mechanical irritation Inflammation Compression due to edema Ischemia Migrating mesh stretched a nerve Bendavid, R. , Lou, W. , Koch, A., Iakovlev, V. Mesh-Related SIN Syndrome. A Surreptitious Irreversible Neuralgia and Its Morphologic Background in the Etiology of Post-Herniorrhaphy Pain. International Journal of Clinical Medicine, 2014, 5:799-810

Nerve ingrowth with entrapment Possible pain mechanisms Nerve ingrowth with entrapment

Nerve ingrowth with entrapment Possible pain mechanisms Nerve ingrowth with entrapment

Possible/contributing pain mechanisms Inflammation

Mesh hardening, shrinking, attachment to tissues Possible/contributing pain mechanisms Mesh hardening, shrinking, attachment to tissues

Possible/contributing pain mechanisms Edema within mesh compartments Mini-compartment syndrome?

Ischemic pain or ischemia driven scar expansion? Possible/contributing pain mechanisms Ischemic pain or ischemia driven scar expansion?

Interposition with striated muscle Possible/contributing pain mechanisms Interposition with striated muscle

Mesh migration into organs and tissue deformation Possible/contributing pain mechanisms Mesh migration into organs and tissue deformation

Mesh migration into organs and tissue deformation Possible/contributing pain mechanisms Mesh migration into organs and tissue deformation

Conclusions Innervated tissue is exposed to all regular pain mechanisms Density of ingrown nerves is higher in hernia meshes removed for reasons of pain than in meshes removed for recurrence Nerve entrapment appears to be one of the main mechanisms of pain for these patients Other possible or contributing factors are: Inflammation Mesh hardening, shrinking and attachment to tissues Edema within mesh compartments Muscle interposition Ischemia Important to answer these questions to guide future technical development and treatment strategies

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