Year: 2008
Type: dissertation
Abstract: ABSTRACT \nThe aim of my thesis is to further investigate the mechanisms underlying inflammatory \nmuscle pain. Despite numerous studies investigating the mechanisms of inflammatory \nhyperalgesia, little is known of the mechanisms underlying inflammatory muscle \nhyperalgesia. Using rats as experimental animals, I investigated inflammatory hyperalgesia \nin muscle and compared it to that of inflamed cutaneous tissue. I injected carrageenan, a \nplant-origin polysaccharide, into leg muscle and into the hind paw of rats, and measured \nthe behavioural response, as well as cytokine changes, in both plasma and inflamed tissue. \nCarrageenan induced inflammatory hyperalgesia but the cytokine cascade was not the same \nin muscle and cutaneous tissue. At no time following carrageenan injection was muscle \ntumour necrosis factor alpha (TNF-&) concentration elevated above that of muscle injected \nwith saline. TNF-& is a key inflammatory mediator in cutaneous tissue, but apparently not \nin muscle. Interleukin-1) (IL-1)) and interleukin-6 concentrations also were different \nduring muscle inflammation compared to those of cutaneous inflammation. IL-1) and IL- \n6 concentrations, following carrageenan injection, were elevated later in muscle compared \nto in cutaneous tissue. IL-1) is a potent sensitizer of nociceptors in cutaneous tissue, and \nalso may play an important role in sustaining muscle pain, but it is unlikely to be an initiator \nof the inflammatory muscle hyperalgesia. In the course of comparing muscle hyperalgesia \nand cutaneous hyperalgesia, I aimed to identify whether these differences in cytokine \nconcentrations were unique to muscle tissue or if similar differences in cytokine \nconcentrations existed between the hind paw and other cutaneous sites. To explore an \nalternative cutaneous tissue site, I injected carrageenan into the rat tail and measured the \nbehavioural response, changes in cytokine concentrations and histological changes. \nElevations of pro-inflammatory cytokines occurred concurrently with the infiltration of leukocytes into the inflamed tail tissue with the thermal and mechanical hyperalgesia similar to that found in the hind paw. Different mechanisms therefore appear to underlie muscle \nand cutaneous inflammatory hyperalgesia, regardless of the site used to investigate \ncutaneous inflammation. One of the consequences of the poor understanding of muscle \npain is the lack of a reliable regimen for treating human muscle pain, including delayedonset \nmuscle soreness (DOMS). DOMS, which has a partial inflammatory pathogenesis, is \nnot relieved by non-selective cyclo-oxygenase inhibitors. This phenomenon may be that \nprostaglandins are not produced peripherally or centrally, when muscle tissue is damaged. I \ninvestigated the effect of inhibiting cyclo-oxygenase-2, the isoform released during \ninflammation, on DOMS in human volunteers. I found that rofecoxib, a cyclo-oxygenase-2 \ninhibitor, did not attenuate DOMS and nor did tramadol, a central-acting analgesic. The \nneurochemical pathway underlying DOMS therefore appears to be distinct from the \npathways which underlie pain and hyperalgesia in other syndromes. Future research should \ninclude investigations into the central mechanisms of muscle pain and blocking the action \nof IL-1) and CINC-1 both peripherally and centrally may prove a beneficial target for the \ntreatment of clinical muscle pain.
Author: Lisa C. Loram
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Research Foundation
OpenAlex ID: W175633131