Resolution of Inflammation by Resolvin D1 Is Essential for Peroxisome Proliferator–activated Receptor-γ–mediated Analgesia during Postincisional Pain Development in Type 2 Diabetes

Saito, Takayuki; Hasegawa-Moriyama, Maiko; Kurimoto, Tae; Yamada, T.; Inada, Eichi; Kanmura, Yuichi

doi:10.1097/aln.0000000000000892

Cited by 23 publications

(26 citation statements)

References 48 publications

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“…However, several studies suggest that pioglitazone can inhibit peripheral mechanisms of chronic pain: 1) PPARγ is expressed in sciatic nerve 110 ; 2) TZDs decreased hyperalgesia, proinflammatory cytokine expression, and macrophage infiltration in sciatic nerve after nerve injury 55, 96 ; 3) Pioglitazone reduced macrophage infiltration and pERK expression into the sciatic nerve of STZ rats 110 ; 4) Pioglitazone reduced pERK expression in sciatic nerve of db/db mice 15 ; and 5) Rosiglitazone and resolvin D1 coadministration to the site of hindpaw incision in db/db mice promotes a M2 macrophage phenotype and reduces mechanical hypersensitivity 82 . Future studies in preclinical models of type 2 PDN could investigate the effect of local TZD administration to the peripheral nerve 31, 96 on: macrophage polarization 31 ; TNFα, which is elevated in patients with PDN 74, 99 ; nerve conduction velocity, which is decreased in type 2 diabetes 6 ; and pain-like behaviors.…”

Section: Discussionmentioning

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

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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%

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

“…Similarly, M1 macrophages in the spinal cord contribute to chronic pain in rodent model of spinal cord injury (Willemen et al, 2012;Kigerl et al, 2009). Moreover, the induction of an M2 macrophage phenotype reverses or prevents the development of pain and inflammation in rodent models of paw incision and diabetes (Saito et al, 2015), acid-induced muscle pain (Leung et al, 2015), carrageenan-induced inflammation (Willemen et al, 2012) or spinal cord injury (Willemen et al, 2012;Kigerl et al, 2009). In humans (Brueckmann et al, 2004) and mice (Khallou-Laschet et al, 2010), the extended presence of M1 macrophages and a systemic inflammatory response are associated with the development of atherosclerosis and acute coronary syndrome.…”

Section: Introductionmentioning

confidence: 97%

Evaluation of a nanotechnology-based approach to induce gene-expression in human THP-1 macrophages under inflammatory conditions

et al. 2017

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Macrophages orchestrate the initiation and resolution of inflammation by producing pro- and anti-inflammatory products. An imbalance in these mediators may originate from a deficient or excessive immune response. Therefore, macrophages are valid therapeutic targets to restore homeostasis under inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle effectively induces gene expression in human macrophages under inflammatory conditions without undesirable immunogenic responses. THP-1 macrophages were challenged with lipopolysaccharide (LPS, 5μg/mL). Polyethylenimine (PEI) nanoparticles grafted with a mannose receptor ligand (Man-PEI) were used as a gene delivery method. Nanoparticle toxicity, Man-PEI cellular uptake rate and gene induction efficiency (GFP, CD14 or CD68) were studied. Potential immunogenic responses were evaluated by measuring the production of tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-10. Man-PEI did not produce cytotoxicity, and it was effectively up-taken by THP-1 macrophages (69%). This approach produced a significant expression of GFP (mRNA and protein), CD14 and CD68 (mRNA), and transiently and mildly reduced IL-6 and IL-10 levels in LPS-challenged macrophages. Our results indicate that Man-PEI is suitable for inducing an efficient gene overexpression in human macrophages under inflammatory conditions with limited immunogenic responses. Our promising results set the foundation to test this technology to induce functional anti-inflammatory genes.

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“…29,37,38,47,49,51 Resolvins have direct actions on the recruitment and migration of neutrophils and macrophages, underlying the resolution phase of inflammation 48,51–53 , and they also alter peripheral and central nervous system responses to inflammation and injury, through direct actions on neurons and glia. 65 Since the drugs that are traditionally used to treat inflammatory and post-operative pain, namely opiates and cyclo-oxygenase-2 (COX-2) inhibitors, have unwanted side effects, there is a need to find new approaches and compounds that will be more selective in their actions and have fewer adverse actions.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Chronic Post-Thoracotomy Pain in Rats By Intrathecal Resolvin D1 and D2: Effectiveness of Perioperative and Delayed Drug Delivery

Wang

Strichartz

2017

The Journal of Pain

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Thoracotomy results in a high frequency of chronic post-operative pain. Resolvins are endogenous molecules, synthesized and released by activated immune cells, effective against inflammatory and neuropathic pain. Different resolvins have differential actions on selective neuronal and glial receptors and enzymes. This paper examines the ability of intrathecal Resolvin D1 (RvD1) and Resolvin D2 (RvD2) to reduce chronic postthoracotomy pain in rats. Thoracotomy, involving intercostal incision and rib retraction, resulted in a decrease in the mechanical force threshold to induce nocifensive behavior, an enlargement of the pain-sensitive area, and an increase in the fraction of rats showing nocifensive behavior, all for at least 5 weeks. The qualitative nature of the behavioral responses to tactile stimulation changed dramatically after thoracotomy, including the appearance of vigorous behaviors, such as turning, shuddering, and squealing, all absent in naive rats. Intrathecal delivery of RvD1 (30ng/30µL), at surgery or 4 days later, halved the spread of the mechano-sensitive area, lowered by 60% the percent of rats with tactile hypersensitivity, and reduced the drop in threshold for a nocifensive response, along with a reduction in the occurrence of vigorous nocifensive responses. RvD2’s actions on threshold changes were statistically the same. These findings suggest that intrathecal resolvins, delivered pre-operatively or several days later, can prevent chronic post-operative hyperalgesia.

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Resolution of Inflammation by Resolvin D1 Is Essential for Peroxisome Proliferator–activated Receptor-γ–mediated Analgesia during Postincisional Pain Development in Type 2 Diabetes

Abstract: In diabetes, exogenous administration of RvD1 is essential for PPARγ-mediated analgesia during development of postincisional pain. Resolution of inflammation accelerated by RvD1 might promote PPARγ-mediated macrophage polarization to the M2 phenotype.

Cited by 23 publications

References 48 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

Evaluation of a nanotechnology-based approach to induce gene-expression in human THP-1 macrophages under inflammatory conditions

Prevention of Chronic Post-Thoracotomy Pain in Rats By Intrathecal Resolvin D1 and D2: Effectiveness of Perioperative and Delayed Drug Delivery

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