Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (p. 83-92).

No description available.

No description available.

Ph.D.

Cattle lameness is the biggest disease problem facing dairy farmers in the United Kingdom at this time. Current figures show that over 50 per cent of dairy cattle become clinically lame each year. In addition to the loss of productivity associated with lameness the question of whether the animals welfare is compromised through pain and suffering associated with lameness needs to be addressed. Also how relief from such suffering can be approached using the resources available to the modem dairy farmer and veterinary surgeon. Many diseases of the claws and lower limbs of cattle with differing aetiology and pathogenesis are brought together under the heading of lower limb lameness. Fifteen different lesions are commonly seen with many more occurring sporadically. The lameness ranges from acute to chronically persistent often with similar lesions seen in repeated lactations. During an episode of lameness the cow is frequently expected to continue to compete for nutrition and lying space within the herd environment and, during the summer months, to walk long distances to and from pasture. This is a management approach which is likely to decrease the welfare and increase the suffering of a lame dairy cow. The aim of the study was to evaluate the changes in behaviour of dairy cattle which are associated with lameness by locomotion and lameness scoring, the observation of spontaneous behaviours and changes in demeanour. To then relate these changes to parameters such as nociceptive threshold, lesion type and claw pathology, endocrine response and changes in weight bearing. Also, to study the effects of analgesics on these behaviours and objective parameters. In so doing to build up a picture of the animal's perception of the pain associated with lameness. The results showed that parturition represented a period of high risk for the appearance of claw lesions and the onset of lameness in dairy heifers. Clinical lameness in lactating dairy cows was associated with a decrease in mechanical nociceptive thresholds indicating the presence of hyperalgesia in these animals. The hyperalgesia persisted in cattle with chronic claw diseases up to 28 days after the lesion was treated and behavioural signs of lameness were no longer present but was not later detected in those individuals with acute digital tissue infections. The administration of a Non-Steroidal Anti-inflammatory Drug with analgesic properties to cattle with a hind limb lameness resulted in a significant modulation in the level of hyperalgesia over a 28 day period. This modulation was not observed in lame cattle who were given a control treatment of Sterile Saline in association with a programme of conventional treatment. Postural changes associated with lameness were ameliorated through a conventional treatment programme while the demeanour of the lame animals was seen to improve when offered analgesia concurrently with treatment. In summary, chronically lame cattle were found to be in a persistent hyperalgesic state indicative of pain. Further evidence of suffering was provided by behavioural observation and the evidence of some, but not total, relief from pain through the administration of analgesia. It could therefore be concluded that there is pain associated with lameness which is likely to cause the animal suffering. In the future a more integrated approach to the treatment, management and analgesia of lame cattle is required to provide relief from this suffering

ABSTRACT The aim of my thesis is to further investigate the mechanisms underlying inflammatory muscle pain. Despite numerous studies investigating the mechanisms of inflammatory hyperalgesia, little is known of the mechanisms underlying inflammatory muscle hyperalgesia. Using rats as experimental animals, I investigated inflammatory hyperalgesia in muscle and compared it to that of inflamed cutaneous tissue. I injected carrageenan, a plant-origin polysaccharide, into leg muscle and into the hind paw of rats, and measured the behavioural response, as well as cytokine changes, in both plasma and inflamed tissue. Carrageenan induced inflammatory hyperalgesia but the cytokine cascade was not the same in muscle and cutaneous tissue. At no time following carrageenan injection was muscle tumour necrosis factor alpha (TNF-&) concentration elevated above that of muscle injected with saline. TNF-& is a key inflammatory mediator in cutaneous tissue, but apparently not in muscle. Interleukin-1) (IL-1)) and interleukin-6 concentrations also were different during muscle inflammation compared to those of cutaneous inflammation. IL-1) and IL- 6 concentrations, following carrageenan injection, were elevated later in muscle compared to in cutaneous tissue. IL-1) is a potent sensitizer of nociceptors in cutaneous tissue, and also may play an important role in sustaining muscle pain, but it is unlikely to be an initiator of the inflammatory muscle hyperalgesia. In the course of comparing muscle hyperalgesia and cutaneous hyperalgesia, I aimed to identify whether these differences in cytokine concentrations were unique to muscle tissue or if similar differences in cytokine concentrations existed between the hind paw and other cutaneous sites. To explore an alternative cutaneous tissue site, I injected carrageenan into the rat tail and measured the behavioural response, changes in cytokine concentrations and histological changes. Elevations 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 and cutaneous inflammatory hyperalgesia, regardless of the site used to investigate cutaneous inflammation. One of the consequences of the poor understanding of muscle pain is the lack of a reliable regimen for treating human muscle pain, including delayedonset muscle soreness (DOMS). DOMS, which has a partial inflammatory pathogenesis, is not relieved by non-selective cyclo-oxygenase inhibitors. This phenomenon may be that prostaglandins are not produced peripherally or centrally, when muscle tissue is damaged. I investigated the effect of inhibiting cyclo-oxygenase-2, the isoform released during inflammation, on DOMS in human volunteers. I found that rofecoxib, a cyclo-oxygenase-2 inhibitor, did not attenuate DOMS and nor did tramadol, a central-acting analgesic. The neurochemical pathway underlying DOMS therefore appears to be distinct from the pathways which underlie pain and hyperalgesia in other syndromes. Future research should include investigations into the central mechanisms of muscle pain and blocking the action of IL-1) and CINC-1 both peripherally and centrally may prove a beneficial target for the treatment of clinical muscle pain.

No description available.

No description available.

The primary aim of this study was to determine the effect of high frequency Transcutaneous Electrical Nerve Stimulation (TENS) on cold sensory function following topical application of menthol. Quantitative sensory testing was used to determine cold sensation and cold pain thresholds before and after topical application of a 40% menthol solution in 9 male and 11 female subjects. In a separate session the effect of TENS (100 HZ, constant pulse, 100µs, 20 minutes) was determined on menthol-induced cold sensation. Menthol produced a distinct cold hyperalgesia which was significantly reduced during the application of high frequency TENS. The analgesic effect of TENS persisted beyond the application period for at least 20 minutes. Menthol also reduced cold detection thresholds but TENS had no effect on this aspect of cold sensation. These data support the use of TENS as a means of treating cold hyperalgesia such as that found in neuropathic pain states.