Thermal, But Not Mechanical, Nociceptive Behavior is Altered in the Zucker Diabetic Fatty Rat and Is Independent of Glycemic Status

Piercy, Valerie; Banner, S.E.; Bhattacharyya, Amit; Parsons, Andrew A.; Sanger, Gareth J.; Smith, Stephen A.; Bingham, Sharon

doi:10.1016/s1056-8727(99)00034-3

Cited by 28 publications

(27 citation statements)

References 20 publications

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“…When compared to control heterozygotes or wild-types, only ZDF rats homozygous for the fatty (fa/fa) leptin receptor mutation develop cardinal symptoms of glucose-intolerant diabetes 13 including hyperphagia 69,83 , hyperinsulinemia 51, 65, 92 , obesity 69 , hyperglycemia 69, 73, 101 , elevated HbA1c 51, 92 , and increased MG-AGE 89 . In the first experiment we characterized the progression of hyperglycemia and pain-like behavior in diabetic ZDF and control ZL rats.…”

Section: Resultsmentioning

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: Resultsmentioning

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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show abstract

“…However, Piercy et al 29 as well as Oltman et al 30 included a treatment group with rosiglitazone, another PPARg agonist, and did not observe any difference between treated and untreated obese ZDF rats with respect to sensory thresholds. While Oltman et al initiated rosiglitazone treatment after diabetes manifestation and so could not improve the glycaemic state of the ZDF rats, Piercy et al started treatment at eight weeks of age in a prediabetic state, keeping the rats euglycaemic throughout the study period.…”

Section: Discussionmentioning

confidence: 97%

Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications

Hempe

Elvert

et al. 2012

Lab Anim

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Male obese Zucker Diabetic Fatty (ZDF) rats develop type 2 diabetes around eight weeks of age, and are widely used as a model for human diabetes and its complications. The objective of the study was to test whether the complications manifested in the kidney and nerves of ZDF rats really correspond to human diabetic complications in their being related to the hyperglycaemic state. Four groups of ZDF rats were used. One lean (Fa/?) and one obese (fa/fa) untreated group served as non-diabetic and diabetic controls. In two further groups of obese (fa/fa) rats, diabetes was prevented by pioglitazone or delayed by food restriction. All rats were monitored up to 35 weeks of age with respect to their blood glucose, HbA1c and insulin levels, their kidney function (urinary glucose excretion, renal glucose filtration, glomerular filtration rate, albumin/creatinine ratio), and their nerve function (tactile and thermal sensory threshold and nerve conduction velocity). Pioglitazone prevented the development of diabetes, while food restriction delayed its onset for 8-10 weeks. Accordingly, kidney function parameters were similar to lean non-diabetic rats in pioglitazone-treated rats and significantly improved in food-restricted rats compared with obese controls. Kidney histology paralleled the functional results. By contrast, nerve functional evaluations did not mirror the differing blood glucose levels. We conclude that the ZDF rat is a good model for diabetic nephropathy, while alterations in nerve functions were not diabetes-related.

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“…Earlier studies demonstrated that female obese Zucker rats with fasting normoglycaemia, aged 17-21 weeks, developed thermal hyperalgesia as indicated by a decreased TFL [34]. In addition, in ZDF rats, thermal hyperalgesia, as indicated by a decrease in paw fanning or licking latency to a noxious thermal (hot plate) stimulus, occurred by 9 weeks of age and was not prevented by the insulin sensitizer rosiglitazone which maintained normoglycaemia [35]. Collectively, these findings suggest that early nociceptive dysfunction is characterized by thermal hyperalgesia and is independent of chronic hyperglycaemia in rat models of IR.…”

Section: Discussionmentioning

confidence: 99%

Time course of pain sensation in rat models of insulin resistance, type 2 diabetes, and exogenous hyperinsulinaemia

Sugimoto

Rashid

Kojima

et al. 2008

Diabetes Metabolism Res

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Thermal, But Not Mechanical, Nociceptive Behavior is Altered in the Zucker Diabetic Fatty Rat and Is Independent of Glycemic Status

Cited by 28 publications

References 20 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

Appropriateness of the Zucker Diabetic Fatty rat as a model for diabetic microvascular late complications

Time course of pain sensation in rat models of insulin resistance, type 2 diabetes, and exogenous hyperinsulinaemia

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