Abstract
BackgroundEmerging evidence has demonstrated that inflammation is involved in the occurrence and development of diabetic neuropathic pain (DNP). The anti-inflammatory property of interleukin (IL)-35 makes it a promising candidate to block the pain perception. The present study was undertaken to investigate whether IL-35 could attenuate DNP in streptozotocin (STZ)-induced rat model and its potential mechanism.MethodsThe rat model of DNP was established by a single STZ injection followed by measurements of fasting blood glucose and insulin. Fourteen days after STZ injection, DNP rats were intrathecally injected with IL-35, c-Jun N-terminal kinase (JNK) inhibitor or activator or dimethylsulfoxide (DMSO) as vehicle control, respectively. The mechanical allodynia was assayed to evaluate the therapeutic effect of IL-35. In mechanism study, the serum and protein levels of inflammatory cytokines using ELISA and western blotting and the activation of JNK signaling were further evaluated by quantitative reverse transcription PCR (qRT-PCR). Histopathologic changes were evaluated by Nissl staining. Apoptosis was examined using TUNEL staining.ResultsDNP rats exhibited increased fasting blood glucose and insulin levels and reduced insulin sensitivity index (ISI). Intrathecal injection of IL-35 reduced accumulation of pro-inflammatory cytokines in the spinal cord of DNP rats. Furthermore, IL-35 displayed anti-inflammatory and anti-apoptotic effects via inhibition of JNK pathway.ConclusionIL-35 treatment mitigated DNP via downregulating JNK signaling pathway.
Highlights
Diabetes is a common chronic metabolic disease threatening human health
Diabetic neuropathic pain (DNP) is one of the most common chronic complications of diabetes, which is characterized by spontaneous pain, hyperalgesia, and allodynia, affecting more than 50% of patients living with diabetes [2]
Fasting plasma glucose and insulin levels were increased while insulin sensitivity index (ISI) was reduced in diabetic neuropathic pain (DNP) rats As shown in Table 1, compared to the control group, the concentration of serum glucose in DNP group was significantly elevated after 8 weeks of feeding
Summary
Diabetes is a common chronic metabolic disease threatening human health. With the improvement of people’s living standard, the aggravation of ageing population and the alteration of people’s life style, the prevalence of diabetes is gradually increasing [1]. Diabetic neuropathic pain (DNP) is one of the most common chronic complications of diabetes, which is characterized by spontaneous pain, hyperalgesia, and allodynia, affecting more than 50% of patients living with diabetes [2]. There are mainly three MAPK signaling pathways in mammalian cells, including extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38-MAPK, which are known to participate in the generation of pain hypersensitivity [5]. It is noteworthy that JNK-c-Jun signaling pathway is essential for chronic inflammatory pain [6]. Emerging evidence has demonstrated that inflammation is involved in the occurrence and development of diabetic neuropathic pain (DNP). The present study was undertaken to investigate whether IL-35 could attenuate DNP in streptozotocin (STZ)-induced rat model and its potential mechanism
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