Role of Functional Brain Imaging in Understanding Rheumatic Pain

Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are common and debilitating chronic pain syndromes. Recently, human functional neuroimaging, for example EEG, fMRI, and PET has begun to reveal some of the crucial central nervous system mechanisms underlying these diseases. The purpose of this review is to summarise current knowledge on the brain mechanisms of rheumatic pain revealed by functional neuroimaging techniques. The evidence suggests that two mechanisms may be largely responsible for the clinical pain associated with these rheumatic diseases: abnormalities in the medial pain system and/or central nervous system sensitisation and inhibition. If we can understand how functioning of the central nociceptive system becomes altered, even in the absence of peripheral nociceptive input, by using functional neuroimaging techniques, in the future we may be able to develop improved, more effective treatments for patients with chronic rheumatic pain.     

EFFECT OF CHRONIC EXPOSURE TO GASEOUS AMMONIA ON THE NASAL TURBINATES OF GNOTOBIOTIC PIGS

Pigs reared in and stock persons working in intensive production systems are continuously exposed to ammonia released by microbial degradation of animal excrement. Experimental studies have shown that exposure to this gas, at concentrations comparable to those encountered in buildings used for the intensive rearing of swine, increases the severity of the clinical disease progressive atrophic rhinitis in pigs by facilitating colonization of the upper respiratory tract by toxigenic Pasteurella multocida. During the course of these studies it was observed that mild turbinate atrophy also occurred in pigs from control groups exposed to ammonia but maintained free from P. multocida and Bordetella bronchiseptica. To determine whether exposure to ammonia is detrimental to the normal anatomical development of the mammalian nasal cavity, a study was conducted using gnotobiotic piglets. Twenty-one gnotobiotic piglets were derived from two sows by hysterectomy. Each litter was split into two groups, and the four groups were accommodated separately in sterile positive-pressure isolators supplied with high-efficiency particulate air (HEPA) filtered air. From 1 wk of age onward the air in the isolators housing one of the groups from each litter was modified by the addition of ammonia at a concentration of 9.1 and 15.7 ppm. The air supply to the isolators housing the littermate groups was not modified. At 6 wk of age all the pigs were euthanatized. The effect of ammonia exposure on the morphology of the nasal cavity of the pig was assessed by image analysis of a cross section of the pig's snout. Pigs exposed to ammonia were found to have a mild but statistically significant level of turbinate atrophy when compared to nonexposed lit termates. Histological examination revealed that prolonged ammonia exposure evoked changes to the mucous membranes lining the nasal cavity, characterized by epithelial hyperplasia with micro-abscess formation, goblet-cell hypoplasia, and inflammatory cell infiltration. Mild degenerative changes within the bony core of the ventral turbinate were also apparent, with a decline in the population of osteoblasts and simultaneous osteoclast proliferation. Group analysis revealed a correlation between the severity of turbinate atrophy and the increase in the number of osteoclasts per unit area of bony core (p<.05). These findings could explain why mild turbinate atrophy is seen on some pig units deemed free from pathogenic bacteria associated with the clinical disease atrophic rhinitis.