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

Experimental physiology, 2012-11, Vol.97 (11), p.1236-1245 [Peer Reviewed Journal]

2012 The Authors. Experimental Physiology © 2012 The Physiological Society ;ISSN: 0958-0670 ;EISSN: 1469-445X ;DOI: 10.1113/expphysiol.2011.064220 ;PMID: 22523380

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Title:
Increased central and peripheral inflammation and inflammatory hyperalgesia in Zucker rat model of leptin receptor deficiency and genetic obesity
Author: Iannitti, Tommaso ; Graham, Annette ; Dolan, Sharron
Subjects: Adiponectin - genetics ; Adiponectin - metabolism ; Animals ; Capsaicin - pharmacology ; Carrageenan - pharmacology ; Down-Regulation - drug effects ; Down-Regulation - genetics ; Edema - chemically induced ; Edema - genetics ; Edema - metabolism ; Edema - pathology ; Hyperalgesia - chemically induced ; Hyperalgesia - genetics ; Hyperalgesia - metabolism ; Hyperalgesia - pathology ; Inflammation - chemically induced ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - pathology ; Interleukin-1beta - genetics ; Interleukin-1beta - metabolism ; Male ; Morphine - pharmacology ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Nociception - drug effects ; Nociception - physiology ; Obesity - genetics ; Obesity - metabolism ; Obesity - pathology ; Pain - genetics ; Pain - metabolism ; Pain - pathology ; Pain Measurement - methods ; Prostaglandin-Endoperoxide Synthases - genetics ; Prostaglandin-Endoperoxide Synthases - metabolism ; Rats ; Rats, Zucker ; Receptors, Leptin - deficiency ; Receptors, Leptin - genetics ; Receptors, Leptin - metabolism ; RNA, Messenger - genetics ; Spinal Cord - metabolism ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - metabolism ; Up-Regulation - drug effects ; Up-Regulation - genetics
Is Part Of: Experimental physiology, 2012-11, Vol.97 (11), p.1236-1245
Description: 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.
Publisher: Oxford, UK: Blackwell Publishing Ltd
Language: English
Identifier: ISSN: 0958-0670
EISSN: 1469-445X
DOI: 10.1113/expphysiol.2011.064220
PMID: 22523380
Source: Journals@Ovid Open Access Journal Collection Rolling
GFMER Free Medical Journals
MEDLINE

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

2012 The Authors. Experimental Physiology © 2012 The Physiological Society ;ISSN: 0958-0670 ;EISSN: 1469-445X ;DOI: 10.1113/expphysiol.2011.064220 ;PMID: 22523380

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