Patterns of Nerve Fibre Impairments and Neuronal Activation in Male Diabetic Rats With and Without Mechanical Allodynia: A Comparative Study

Abstract

BackgroundIt is still clinically difficult to definitively distinguish between painful and nonpainful diabetic peripheral neuropathy (DPN). In this study, pain patterns were further categorized; diabetic rats were grouped according to the presence or absence of mechanical allodynia (MA), which is a hallmark of neuropathic pain, and comparisons were made between diabetic rats with and without MA. MethodsDiabetes was established in rats by a single intraperitoneal streptozotocin injection, and vehicle injection was administered in the control group. Pain behaviour tests for MA and thermal hyperalgesia were performed every week. At week 4, the diabetic group with thermal hyperalgesia was further grouped by the presence of MA. Morphometric analysis of sciatic nerves and myelin basic protein quantification were conducted. The numbers of c-Fos–immunoreactive neurons in both the dorsal root ganglion (DRG) and the spinal dorsal horn (SDH) were determined. ResultsDiabetic rats with MA had more severe impairment of myelinated nerve fibres than those without MA (p<0.001). Higher percentages of NF-200–positive neurons in the DRG were c-Fos immunoreactive in the DPN-with-MA group than in the DNP-without-MA group (p=0.014). The numbers of c-Fos–immunoreactive neurons in both the superficial (I–II) and deeper (III–V) laminae of the SDH in the DPN-with-MA group were larger than those in the subgroups without MA (p<0.001). ConclusionsThe impairment of primary myelinated fibres and the pattern of neuronal activation in both the DRG and the SDH are specific features that differentiate diabetic rats with MA from those without MA.