title: Supraspinal metabolic activity changes in the rat during adjuvant monoarthritis.
abstract: Pain is a multi-dimensional experience including sensory-discriminative and affective-motivational components. The attribution of such components to a corresponding cerebral neuronal substrate in the brain refers to conclusions drawn from electrical brain stimulation, lesion studies, topographic mappings and metabolic imaging. Increases in neuronal metabolic activity in supraspinal brain regions, suggested to be involved in the central processing of pain, have previously been shown in various animal studies. The present investigation is the first to describe supraspinal structures which show increased metabolic activity during ongoing monoarthritic pain at multiple time-points. Experimental chronic monoarthritis of a hindlimb induced by complete Freund's adjuvant is one of the most used models in studies of neuronal plasticity associated with chronic pain. Such animals show typical symptoms of hyperalgesia and allodynia for a prolonged period. Metabolic activity changes in supraspinal brain regions during monoarthritis were assessed using the quantitative [14C]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats which were mechanically stimulated by repeated extensions of the inflamed joint. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal levels, and compared with saline-injected controls. At two and 14 days of monoarthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, limbic and cortical regions. Within the brainstem, animals with 14-day monoarthritis showed a higher number of regions with increased metabolic activity compared with two days. No differences between ipsi- and contralateral sides were detected in any of the experimental groups. Average increases ranged from 20 to 40% compared with controls and maximum values were detected in specific brain regions, such as the anterior pretectal nucleus, the anterior cingulate cortex and the nucleus accumbens. Interestingly, at four days of monoarthritis, the glucose utilization values were in the control range in almost all regions studied. Moreover, in monoarthritic rats receiving an additional noxious mechanical stimulation, the rates of glucose utilization were also comparable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cord, described in the accompanying report. The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful monoarthritis, with a non-linear profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input arising from the monoarthritis and accompanying its development.
authors.affiliation: Institute of Histology and Embryology and IBMC, Faculty of Medicine of Oporto, Porto, Portugal.
authors.forename: F L
authors.initials: FL
authors.lastname: Neto
authors.forename: J
authors.initials: J
authors.lastname: Schadrack
authors.forename: A
authors.initials: A
authors.lastname: Ableitner
authors.forename: J M
authors.initials: JM
authors.lastname: Castro-Lopes
authors.forename: P
authors.initials: P
authors.lastname: Bartenstein
authors.forename: W
authors.initials: W
authors.lastname: Zieglgänsberger
authors.forename: T R
authors.initials: TR
authors.lastname: Tölle
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000503:physiopathology; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003847:Deoxyglucose / Q000493:pharmacokinetics*; D008297:Male; D015999:Multivariate Analysis; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D003847:Deoxyglucose