Association of myelinated primary afferents impairment with mechanical allodynia in diabetic peripheral neuropathy: an experimental study in rats

Abstract

To investigate the mechanisms underlying the efficacy of surgical treatment for painful diabetic peripheral neuropathy. Rats were initially divided into 3 groups (I, control rats, II, streptozotocin-induced diabetic rats, III, streptozotocin-induced diabetic rats with latex tube encircling the sciatic nerve without compression). When mechanical allodynia (MA) became stable in the third week, one third of group III rats were sacrificed and the remainder were further divided into subgroups depending on whether the latex tube was removed. Except for some rats in group III, all rats were sacrificed in the fifth week. Morphometric analysis of nerve fibers was performed. Expression level of GABAB receptor protein in spinal dorsal horn was determined. Changes of GABAB receptor within areas of primary afferents central terminal were identified. Chronic nerve compression caused by the interaction of diabetic nerves swelling and the encircling latex tube increased the incidence of MA in diabetic rats, and nerve decompression could ameliorate MA. In diabetic rats with MA, demyelination of myelinated fibers was noted and reduction of GABAB receptor was mainly detected in the area of myelinated afferent central terminals. MA in DPN should be partially attributed to compression impairment of myelinated afferents, supporting the rationale for surgical decompression.

Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression

“…21 However, hyperglycemia and DPN was induced well, with the rats remaining otherwise relatively healthy according to our experience. 22 In the present study, both mechanical allodynia and thermal hyperalgesia were observed to manifest in both STZ-induced diabetic groups. In accordance with previous literature, a high incidence of thermal hyperalgesia (90.0%) and a moderate incidence (57.1%) of mechanical allodynia by STZ-injection were observed.…”

Triple-nerve decompression surgery for the treatment of painful diabetic peripheral neuropathy in lower extremities: A study protocol for a randomized controlled trial

“…Numerous mainstream academic groups, including American Diabetes Association, are strongly advocating for clinical trials with high-level evidence to determine whether surgical decompression is beneficial ( 25 , 26 , 46 ). The present trial is conducted based on our previous clinical and translational studies, in which we investigated the factors associated with a favorable surgical outcome and explored the pathological mechanisms underlying painful DPN ( 17 , 35 , 47 , 48 ). According to our previous clinical practice, diabetic patients with higher VAS are more likely to seek surgical consultants than those with lower VAS.…”