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Title: Obesity, inflammation and pathological pain
Author: Iannitti, Tommaso
ISNI:       0000 0004 2724 9471
Awarding Body: Glasgow Caledonian University
Current Institution: Glasgow Caledonian University
Date of Award: 2011
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Obesity has become a concern of epidemic proportion and is associated with an increased incidence in chronic pain but the underlying mechanism is not known. Obesity is associated with a low-grade inflammation of white adipose tissue due to a dysregulation in cytokines and adipokines, some of which, including turnor necrosis factor-α and interleukin-1β, have been linked to inflammatory pain. Other adipokines such as adiponectin, display anti- inflammatory properties but their role in modulating inflammatory pain has not been investigated. The aim of this project was to characterise inflammatory pain in the Zucker fatty rat (fa/fa) model of obesity and identify a role for adipokines in mediating this process. It is hypothesised that adipokines, particularly adiponectin, which is lowered on the onset of obesity and possesses anti-inflammatory properties, may account for the differences in pain occurring with obesity. Body weights, blood glucose, plasma lipoproteins and serum triacylglycerol, cholesterol, phospholipids and insulin were measured in adult male lean and obese Zucker rats. Hindpaw withdrawal latency (secs) to thermal stimulation and response threshold (grams) to mechanical stimulation were measured before and after intraplantar injection of carrageenan, capsaicin or hindpaw-incision, and treatment with morphine in lean and obese rats. The effects of recombinant adiponectin or drug-vehicle administered intrathecally or intraplantarly on carrageenan-induced pain and inflammation were also measured in adult male Wistar rats. Expression of adiponectin, adiponectin receptor 1, adiponectin receptor 2, resistin, tumor necrosis factor-a, interleukin-Iβ mRNA in spinal cord, brain and adipose tissues and blood was compared in lean and obese rats and in response to intraplantar injection of carrageenan/saline, using polymerase chain reaction methodologies. Obese Zucker rats had increased body weight, serum cholesterol, phospholipid and insulin levels compared to lean rats. No differences in serum triglyceride levels were observed. Following carrageenan-induced inflammation, obese rats were more sensitive to mechanical and thermal stimulation of the inflamed paw, and displayed greater paw oedema compared to lean rats. No difference in capsaicin- or paw-incision induced-mechanical and thermal hyperalgesia or in morphine-induced analgesia was observed. Adiponectin, resistin, adiponectin receptor 1 and adiponectin receptor 2, tumor necrosis factor-a and interleukin-l P mRNA were all found to be constitutively expressed in spinal cord, brain, adipose tissue and blood. In obese rats adiponectin mRNA was down-regulated in spinal cord compared to lean rats, while an increase was observed in brain tissue. A decrease in adiponectin was also observed in paw tissue from carrageenan-treated Wistar rats compared to saline-treated rats. Intrathecal but not intraplantar injection of recombinant adiponectin inhibited mechanical allodynia and carrageenan-induced peripheral inflammation of the paw. The present study confmns that the Zucker fatty rat is a reliable model of obesity with well defined metabolic characteristics. The increase pain sensitivity and inflammatory response in these rats supports the evidence that obesity is a chronic low-grade inflammatory disorder where further inflammatory challenge leads to an augmented inflammatory and nociceptive response. The results strongly suggest that alterations in adipokine-mediated signalling, in particular involving adiponectin, may account for changes in inflammatory pain occurring with obesity making it a valuable target for pain management in these individuals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available