Capsaicin as a source for painful stimulation in functional MRI

Abstract

Functional magnetic resonance imaging (fMRI) was used to examine the brain processing of capsaicin-induced painful stimulation in the alpha-chloralose anesthetized rat. Experiments were performed on a 9.4-T magnet (Magnex, UK) with Avance console (Bruker, Germany) using a surface coil tuned to 400.5 MHz centred over the rat forebrain. Gradient-echo images of two slices, with an echo time of 25 msec, repetition time of 70 msec, and 50 repetitions, were acquired per experiment. These images were analyzed using a fuzzy cluster analysis technique (EvIdent). Activation of areas of the brain known to be associated with the processing of pain, namely the anterior cingulate (bilateral), frontal cortex (bilateral), and sensory motor cortex (contralateral), was found in all animals (N = 6) following injection of 25 microl of capsaicin (128 microg/mL in 7.5% dimethylsulfoxide [DMSO]) into the dorsal forepaw. It is possible to reproduce the pain response in a given animal several times throughout the course of an experiment, provided that sufficient time is allowed between capsaicin injections. This acute phase of capsaicin-induced pain involving stimulation of C polymodal nociceptors was examined by functional imaging. There was a substantial initial increase in activation in regions of the brain associated with pain and there was a trend towards increasing activation with repeated stimulations. Treatment with morphine (3 mg/kg, intravenously) was found to substantially reduce, if not completely eliminate, the areas of functional activation associated with physiologic pain (anterior cingulate and frontal cortex) after C-nociceptor stimulation with capsaicin (N = 6). FMRI involving capsaicin-induced painful stimulation could prove to be an effective tool for the study of novel analgesics and the central nervous system processing of pain.