Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats

Abstract

Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor.

Keywords: Diabetic peripheral neuropathy; allodynia; glia; hyperalgesia; inflammation.

Figure 1

The severity of mechanical allodynia (MA, A) or cold allodynia (CA, B) after streptozotocin or zymosan injection. The severity of MA was divided into 4 groups: severe (<5 g), moderate (5-8 g), mild (8-15 g) and non-pain induction (non, >15 g). The severity of CA was divided into four groups: severe (>16 times), moderate (10-15 times), mild (5-10 times) and non-pain induction (non, <5 times).

Figure 2

The severity of thermal hyperalgesia (TH, A) or mechanical hyperalgesia (MH, B) after streptozotocin or zymosan injection. The severity of TH was divided into 4 groups: severe (<8 sec), moderate (8-16 sec), mild (16-20 sec) and non-pain induction (non, >20 sec). The severity of CA was divided into four groups: severe (<90 g), moderate (90-130 g), mild (130-200 g) and non-pain induction (non, >200 g).

Figure 3

The activation of microglia (CD11b-positive, A-C) and astrocytes (glial fibrillary acidic protein-positive, D-F) following vehicle (A and D), zymosan (B and E) or streptozotocin (C and F) injection. Scale bar=200 µm.