Supraspinal metabolic activity changes in the rat during adjuvant monoarthritis

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 conclusio ns drawn from electrical brain stimulation, lesion studies, topographic map pings and metabolic imaging. Increases in neuronal metabolic activity in su praspinal 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 i ncreased metabolic activity during ongoing monoarthritic pain at multiple t ime-points. Experimental chronic monoarthritis of a hindlimb induced by com plete Freund's adjuvant is one of the most used models in studies of neuron al plasticity associated with chronic pain. Such animals show typical sympt oms of hyperalgesia and allodynia for a prolonged period. Metabolic activit y changes in supraspinal brain regions during monoarthritis were assessed u sing the quantitative [C-14]-2deoxyglucose technique at two, four, 14 days of the disease and, furthermore, in a group of 14-day monoarthritic rats wh ich were mechanically stimulated by repeated extensions of the inflamed joi nt. Local glucose utilization was determined ipsi- and contralateral to the arthritic hindpaw in more than 50 brain regions at various supraspinal lev els, and compared with saline-injected controls. At two and 14 days of mono arthritis significant bilateral increases in glucose utilization were seen in many brain structures, including brainstem, thalamic, Limbic and cortica l regions. Within the brainstem, animals with 14-day monoarthritis showed a higher number of regions with increased metabolic activity compared with t wo 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 cor tex and the nucleus accumbens. Interestingly, at four days of monoarthritis , the glucose utilization values were in the control range in almost all re gions studied. Moreover, in monoarthritic rats receiving an additional noxi ous mechanical stimulation, the rates of glucose utilization were also comp arable to controls in all brain areas investigated. Such patterns of brain metabolic activity agreed with concomitant changes in the lumbar spinal cor d, described in the accompanying report.(112) The present data show that a large array of supraspinal structures displays elevated metabolic activity during painful monoarthritis, with a non-linea r profile for the time-points investigated. This observation most probably reflects mechanisms of transmission and modulation of nociceptive input ari sing from the monoarthritis and accompanying its development. (C) 1999 IBRO . Published by Elsevier Science Ltd.