High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes

Ren, Pengcheng; Zhang, Yong; Zhang, Xudong; An, Lifeng; Lv, Haigang; He, J.; Gao, Changjun; Sun, Xude

doi:10.1016/j.brainresbull.2012.03.002

Cited by 60 publications

(48 citation statements)

References 28 publications

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“…Alternatively, non-PPARγ mechanisms can be proposed for the antihyperalgesic effects of pioglitazone in PDN. Pioglitazone inhibits HMGB1-RAGE signaling in spinal neurons 104 and reduces plasma RAGE 34 , both of which are implicated in the pathogenesis of neuropathic pain in models of traumatic nerve injury 24 and PDN 33, 77 . Whether pioglitazone reduces the contribution of spinal gliosis and/or HMGB1-RAGE signaling to PDN remains an important direction of future studies.…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesized that spinal cord plasticity contributes to pain in type 2 diabetes because: (1) hyperalgesic db/db mice exhibit dorsal horn increases in both phosphorylated extracellular signal-regulated kinase (pERK) 16, 109 , a marker of nociresponsive neuron activation 26 in the spinal dorsal horn 37, 63, 114 , and the astrocyte activation marker GFAP 16, 52, 77, 109 ; (2) intrathecal injection of either the ERK phosphorylation inhibitor U0216 109 or the astrocyte toxin L-α-aminoadipate 52 reverses hyperalgesia; and (3) augmented NMDA and AMPA receptor expression and function in the spinal cord 50 may contribute to hyperalgesia in ob/ob mice 44 . A recent report indicated that spinal neurons in ZDF exhibit central sensitization in response to non-noxious hindpaw stimulation 87 .…”

Section: Introductionmentioning

confidence: 99%

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Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Griggs

Donahue

Adkins

et al. 2016

The Journal of Pain

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Thiazolidinedione drugs (TZDs) such as pioglitazone are FDA-approved for the treatment of insulin resistance in type 2 diabetes. However, whether TZDs reduce painful diabetic neuropathy (PDN) remains unknown. Therefore we tested the hypothesis that chronic administration of pioglitazone would reduce PDN in Zucker Diabetic Fatty (ZDFfa/fa) rats. Compared to Zucker Lean (ZLfa/+) controls, ZDF developed: (1) elevated blood glucose, HbA1c, methylglyoxal and insulin; (2) mechanical and thermal hyperalgesia at the hindpaw; (3) increased avoidance of noxious mechanical probes in a mechanical conflict avoidance behavioral assay, the first report of a measure of affective-motivational pain-like behavior in ZDF; and (4) exaggerated lumbar dorsal horn immunohistochemical expression of pressure-evoked phosphorylated extracellular signal-regulated kinase (pERK). Seven weeks of pioglitazone (30 mg · kg−1 · d−1 in food) reduced blood glucose, HbA1c, hyperalgesia, and pERK expression in ZDF. This is the first report to reveal hyperalgesia and spinal sensitization in the same ZDF animals, both evoked by a noxious mechanical stimulus that reflects pressure pain frequently associated with clinical PDN. As pioglitazone provides the combined benefit of reducing hyperglycemia, hyperalgesia, and central sensitization, we suggest that TZDs represent an attractive pharmacotherapy in patients with type 2 diabetes-associated pain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Griggs

Donahue

Adkins

et al. 2016

The Journal of Pain

View full text Add to dashboard Cite

show abstract

“…For example, the upregulation of HMGB1 in the spinal cord has been shown in different models of chronic pain, including bone cancer (Tong et al, 2010), diabetic painful neuropathy (Ren et al, 2012) and rheumatoid arthritis (Agalave et al, 2014). Similarly, the upregulation of S100β in the spinal cord has also been demonstrated in peripheral pathological conditions, including peripheral nerve injury (Tanga et al, 2006), complete Freund's adjuvant (CFA)-induced paw inflammation ,…”

Section: Involvement Of Glial Cells In Central Sensitizationmentioning

confidence: 97%

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

Kato

Agalave

Svensson

2016

European Journal of Pharmacology

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“…HMGB1 is involved in pathophysiological pain from cancer (Tong et al, 2010), acute appendicitis (Albayrak et al, 2011), type 2 diabetes (Ren et al, 2012), bladder pain (Tanaka et al, 2014), and neuropathic pain (Maeda et al, 2013). Neuropathic pain is caused by nervous system injury and persistent alterations in pain sensitivity.…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

801

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes

Cited by 60 publications

References 28 publications

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Pattern recognition receptors in chronic pain: Mechanisms and therapeutic implications

HMGB1 in health and disease

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