When using noxious heat as a stimulus, some unpredictable things happen.
Hess et al have reported in the Eur J Pain that events associated with central pain are more related to OUTPUT signal tnan INPUT signal. This is very surprising and shows clearly that central pain is coming from central brain structures. It is emanating.
The scientists used BOLD imaging, which stands for blood oxygen dependent levels used for imaging. This can refer to techniques related to PET scans or more commonly with functional MRI (fMRI). fMRI is not widely available. Probably none of you have had it. It remains experimental.
The rats were studied under isoflurane anesthesia. This pretty much rules out the placebo factor, malingering, psychological phenomena and the like. What it rules in is pain, the type we tell our doctors we have, but they have a hard time accepting. The pain was of a peripheral nerve injury model (zymosan injection into the hindpaw), and nerve hypersensitization, but the signal studied was all brain.
The authors reported that “Cingulate, retrosplenial, sensory-motor and insular cortex, medial and lateral posterior thalamic nuclei, pretectal area, hypothalamus and periaqueductal gray were the most consistently, often bilaterally activated regions.” All these areas have been traditionally associated with pain and are not surprising. That this response took place in anesthesthitized rats is, however, a bit unexpected. The pain is operating when the rat is not even conscious. This is a powerful undercutting of the psychological crowd who love to talk of placebo, so much so that they never get around to studying pain chemistry.
Imaging of hyperalgesia in rats by functional MRI.
Hess A, Sergejeva M, Budinsky L, Zeilhofer HU, Brune K.
Department of Experimental and Clinical Pharmacology and Toxicology, Institute for Pharmacology and Toxicology, Fahrstrasse 17, D-91054 Erlangen, Germany.
Cerebral activation in response to sequences of temperature boosts at the hindpaw was observed in functional magnetic resonance imaging (fMRI) experiments in isoflurane anesthetized rats. Cingulate, retrosplenial, sensory-motor and insular cortex, medial and lateral posterior thalamic nuclei, pretectal area, hypothalamus and periaqueductal gray were the most consistently, often bilaterally activated regions. With the same experimental paradigm, activity changes in the brain following subcutaneous zymosan injection into one hindpaw were detected. These changes developed over time (up to 4h) in parallel with the temporal development of hyperalgesia shown by a modified Hargreaves test, thus reflecting processes of peripheral and central sensitization. When the heat stimuli were applied to the inflamed paw, the hyperalgesia manifested itself as a volume increase of the activated areas and/or an enhanced functional blood oxygenation level dependent (BOLD) signal in all the above-mentioned brain regions. Enhanced BOLD signals were also observed in response to stimulation of the contralateral non-injected paw. They were significant in higher associative regions and . This indicates additional sensitization processes in the brain, which we named cerebral sensitization. Long lasting zymosan-induced hyperalgesia could be monitored with high resolution fMRI in rats under isoflurane anaesthesia. This technique may provide an effective method for testing new analgesics and studying structure specific pain processing.
What really shocked us was the finding that the volume increase and stronger BOLD signal were “more pronounced in output-related than in input-related brain structures. This is really central pain, with areas sensitized in the brain, as above mentioned, generating signal which undoubtedly modulates incoming messages from the peripherae. Central pain is an active dynamic process, not merely the failure of some parts of the brain to get involved.
