title: Venous malformation associated nerve profiles and pain: an immunohistochemical study.
abstract: BACKGROUND
  More than 90% of venous malformations (VM) are associated with pain, which is presumed related to phlebolith formation and subsequent nociceptive mediator release. Increasing evidence supports a link between angiogenesis and nerve patterning. Since vascular malformations are aberrations of angiogenesis, it was hypothesised VM pain may be due to differences in nerve profiles associated with these lesions.
  
  
  METHODS
  Immunohistochemical staining was performed on retrospective archival paraffin embedded samples of arteriovenous (AVM; n = 9), capillary (CM; n = 4), lymphatic (LM; n = 29) and VM (n = 14). Antibodies to three nerve markers, neurofilament, S100 and protein gene product 9.5 were employed. Light microscopy was used to assess the density of interstitial nerves and nervi vasorum, and assessments were validated by a second investigator. Significance testing was performed using Mann-Whitney U and Fisher's exact tests.
  
  
  RESULTS
  There was no significant difference in nerve profile between VM and AVM or CM. LM and normal control skin each exhibited a lower nerve density compared to VM (p < 0.0075). The presence of nervi vasorum was found to be lower in VM than normal cutaneous controls when immunostained with S100 antibody (p = 0.044).
  
  
  CONCLUSIONS
  VM-associated pain is unlikely to be due to simple anatomical differences in nerve structure in this condition. As the nerve profile between VM and normal cutaneous control appears to be distinct, further work may elucidate common neurogenic/angiogenic mediators in the pathogenesis of vascular malformations which could prove targets in treating these conditions. In the meantime, current regimes of compression and non-steroidal anti-inflammatory drugs should be continued.
authors: Department of Plastic Surgery at Great Ormond Street Hospital, London WC1N 3JH, UK.
authors: V J
authors: VJ
authors: Gokani
authors: L
authors: L
authors: Kangesu
authors: J
authors: J
authors: Harper
authors: N J
authors: NJ
authors: Sebire
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies; D001165:Arteriovenous Malformations / Q000473:pathology; D002196:Capillaries / Q000002:abnormalities / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D044148:Lymphatic Abnormalities / Q000473:pathology; D008297:Male; D008853:Microscopy; D008875:Middle Aged; D009437:Neuralgia / Q000209:etiology*; D016900:Neurofilament Proteins / Q000276:immunology / Q000378:metabolism; D009418:S100 Proteins / Q000276:immunology / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000276:immunology / Q000378:metabolism; D054079:Vascular Malformations / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D016900:Neurofilament Proteins; D009418:S100 Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase