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Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity.

Abstract：

:This study investigated whether sensitivity to nociceptive stimuli is altered in obese rats using established models of inflammatory pain, and using real-time PCR, profiled alterations in expression of key adipokine and inflammatory mediator mRNA (adiponectin, tumor necrosis factor-α, interleukin-1β, cyclooxygenase-2, inducible nitric oxide synthase (iNOS)) in spinal cord with obesity. Responses to thermal and mechanical stimulation of the hindpaw and paw oedema were assessed in adult male Zucker fatty rats (fa/fa) and their lean littermates (fa/-; n = 6-9 per group) in the absence of inflammation (acute nociception), then in response to intradermal hindpaw injection of carrageenan (3%; 50 μl) or capsaicin (10 μg; 50 μl) or hindpaw incision. The analgesic potency of morphine (1, 2.5 or 5 mg kg(-1) or vehicle; s.c.) was also assessed. Acute nociception was unaltered in obese animals, but following carrageenan-induced inflammation the obese rats were significantly more sensitive to mechanical and thermal stimulation of the inflamed paw, and displayed greater paw oedema. No difference in the capsaicin- or paw-incision-induced pain sensitivity or in the analgesic potency of morphine was observed between groups. Levels of adiponectin and inducible nitric oxide synthase mRNA were downregulated in spinal cord from obese rats, whereas tumour necrosis factor-α mRNA was upregulated; interleukin-1β and cyclo-oxygenase were unchanged. The increased pain sensitivity and inflammatory response together with changes in spinal adipokine expression in obese rats fit well with the hypothesis that obesity is a chronic low-grade inflammatory disorder, producing a state where responses to subsequent inflammatory challenge are potentiated.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Iannitti T,Graham A,Dolan S

doi

10.1113/expphysiol.2011.064220

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

1236-45

issue

eissn

0958-0670

issn

1469-445X

pii

expphysiol.2011.064220

journal_volume

pub_type

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Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity.