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. 2023 Jan 24;14(3):364–375. doi: 10.1111/jdi.13938

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© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Sinomenine inhibits the inositol‐requiring enzyme 1 alpha (IRE1α)–X‐box binding protein 1 (XBP1s) pathway activation by downregulating prostaglandin‐endoperoxide synthase 2 (PTGS2) to relieve pain symptoms in diabetic peripheral neuropathic pain (DPNP) rats. (a) Detection of blood glucose level in DPNP rats. (b) Detection of bodyweight of DPNP rats. (c) Evaluation of the paw withdrawal threshold and paw withdrawal latency of rats before and after streptozotocin injection. (d) The expression of tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β and IL‐6 in rat spinal cord tissue measured by enzyme‐linked immunosorbent assay. (e) Microglia cell activation in the spinal cord of rats measured by immunofluorescence (scale bar: 25 μm). (f) PTGS2 expression in the spinal cord of rats determined by quantitative reverse transcription polymerase chain reaction. (g) The expression of PTGS2, IRE1α and XBP1s in the spinal cord of rats measured by enzyme‐linked immunosorbent assay. (h) PTGS2‐positive cells in the spinal cord of DPNP rats measured using immunofluorescence (scale bar: 25 μm). *P < 0.05 versus the control group. n.s. indicates that the data between the two groups are not statistically significant (n = 10 in each group). DPN, diabetic peripheral neuropathy; NC, normal control; oe, overexpression; SI, sinomenine.