Neurogenic factors in the impaired healing of diabetic foot ulcers.
BACKGROUND
We hypothesize that the reduced innervation of skin can be observed both in clinically neuropathic and non-neuropathic diabetic foot ulcers and can contribute to low inflammatory cell infiltration.


METHODS
Twenty patients with type 2 diabetes and active foot ulcers, without clinical evidence of peripheral sensory neuropathy (n = 12) and with sensory neuropathy (n = 8) were involved in this study. Biopsies from ulcer margin were examined immunohistochemically.


RESULTS
Studies revealed presence of protein gene product 9.5 (PGP9.5)+ nerve endings only in reticular dermis in 3 of 12 non-neuropathic subjects, however, regenerating GAP-43+ endings were seen in dermis of almost all specimens. Lack of substance P+ nerve endings was characteristic for both groups. The reduced distribution of calcitonin gene-related peptide+ nerves in epidermis and dermis was seen mainly in neuropathic group. In neo-epidermis lack of nerve growth factor expression was observed in both groups, whereas neurotrophin 3 immunostaining was characteristic for neuropathic specimens (P < 0.03). Expression of trkA and trkC receptors did not differ significantly between groups. Low inflammatory cell infiltration and moderate presence of fibroblasts was characteristic for all studied specimens.


CONCLUSIONS
The observed reduction of foot skin innervation and neurogenic factors expression can be correlated with low inflammatory cell accumulation and subsequently leads to the observed chronicity of diabetic foot ulcer healing process in both neuropathic and non-neuropathic patients.
Department of Surgical Research and Transplantology, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland. hgalk@cmdik.pan.pl
Hanna
H
Galkowska
Waldemar L
WL
Olszewski
Urszula
U
Wojewodzka
Grzegorz
G
Rosinski
Waldemar
W
Karnafel
D000368:Aged; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017719:Diabetic Foot / Q000473:pathology* / Q000503:physiopathology*; D004817:Epidermis / Q000737:chemistry / Q000294:innervation; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009411:Nerve Endings / Q000737:chemistry; D020933:Neurotrophin 3 / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000294:innervation*; D013373:Substance P / Q000032:analysis; D043222:Ubiquitin Thiolesterase / Q000032:analysis
D019922:GAP-43 Protein; D020933:Neurotrophin 3; C482860:UCHL1 protein, human; D013373:Substance P; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide