Functional relationship between peripheral Aδ-fiber, C-fiber and Aβ-fibers in painful diabetic neuropathy

Abstract

　Background: Diabetic neuropathy ( DN ) has two different phenotypes, painful DN ( PDN ) and painless DN ( PLDN ) . Although the mechanism of pain production in PDN is unclear, peripheral small fiber damage may take part in it. There are two types of small fibers, unmyelinated C-fibers and myelinated Aδ-fibers, and their role in PDN are not clear.　
　Subjects and Methods: We evaluated electrochemical skin conductance ( ESC ) by SUDOSCAN^® and pain threshold of intraepidermal nerve terminal ( PINT ) in 140 patients with diabetes. Simultaneously we scaled abnormality of nerve conduction study by the BDC-index from sural SNAP, tibial CMAP and minimal F-wave latency.　
　Results: ESC, PINT, and BDC-index showed positive correlation with correlation coefficient between 0.67 and 0.77. Among the cases with abnormal ESC and PINT, 20% of the subjects of BDC-0 and -1 groups complained pain, while 40% of the BDC-2, -3, and -4 groups ( p<0.05 ) did it. Among the BDC-0 and -1 patients with abnormal ESC and/or PINT, PDN showed sural SNAP of 6.9±1.2μV, which was lower than 10.6±4.1μV of PLDN ( p<0.01 ) .　
　Interpretation: Abnormal ESC and PINT values represent peripheral C-fiber and Aδ-fiber dysfunction, respectively, while sural SNAP amplitude and BDC-index are determined by large Aβ-fiber density. The two facts that the PDN patients with C- and/or Aδ-dysfunction are more likely in the high BDC group than in the low BDC group, and that SNAP amplitude was lower in PDN than in PLDN among low BDC-patients suggest that spontaneous pain impulses from the impaired C- and Aδ-fibers are suppressed, when input from the Aβ-fibers to the dorsal horn of the spinal cord is sufficient. It is then concluded that Aβ-input reduction to the spinal cord might increases pain-impulse transmission toward the thalamus, which finally produces PDN.