Abstract
Diabetic neuropathy pain (DNP), a spontaneous pain with hyperalgesia and allodynia, greatly compromises patients' quality of life. Our previous study suggested that dexmedetomidine (DEX) can relieve hyperalgesia in rats by inhibiting inflammation and apoptosis at the level of the spinal cord. In the present study, we aimed to evaluate the role of Wnt 10a/β-catenin signaling in DEX-induced alleviation of DNP in rats. Forty-eight rats were randomly allocated to four groups (n=12/group): control, DNP, DEX, and yohimbine groups. The DNP model was established by streptozotocin (STZ) injection. The effects of DEX with or without the α2 adrenergic antagonist yohimbine were assessed by behavior tests (mechanical withdrawal threshold and thermal withdrawal latency). Spinal cord tissue was evaluated by immunofluorescence staining of astrocytes as well as for Wnt 10a and β-catenin expression, western blot analysis of Wnt 10a and β-catenin expression, and enzyme-linked immunosorbent assay measurement of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Rats with STZ-induced DNP had a decreased pain threshold, activated astrocytes, increased expression of Wnt 10a and β-catenin, and increased levels of proinflammatory cytokines compared to the control group, and these effects were ameliorated by treatment with DEX. Yohimbine administration partly abolished the protective effects of DEX in the DNP model rats. In conclusion, DEX alleviated DNP in rats by inhibiting inflammation and astrocyte activation, which may be attributed to downregulation of the Wnt 10a/β-catenin signaling pathway.
Highlights
Many diabetes patients suffer from a common chronic complication known as diabetic neuropathy pain (DNP) [1]
Body weight and blood glucose did not differ significantly among the three treatment groups (Figure 1), which indicates that the changes in these values after model establishment were not influenced by blood glucose only
The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values were significantly lower in the DNP group than in the control group at all-time points
Summary
Many diabetes patients suffer from a common chronic complication known as diabetic neuropathy pain (DNP) [1]. Astrocytes, a type of glial cells, are extensively activated in chronic neuropathy pain and release a large amount of inflammatory mediators that regulate the transmission of pain information [2, 3]. Astrocytes play an important role in the later stage, known as the maintenance stage, of chronic pain. During this stage, inhibiting the activation of astrocytes can effectively relieve the pain [4]. Wnt 10a mediates the activation of classical β-catenin signaling, accounting for pain occurrence [6]. It is unclear whether the Wnt 10a/β-catenin signaling pathway is involved in DNP treatment
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