Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw

Abstract

We examined whether cerebral activation to two different intense and painful stimuli could be detected using functional magnetic resonance imaging (fMRI) in alpha-chloralose anesthetized rats. Experiments were performed using a 9.4 T magnet and a surface coil centered over the forebrain. A set of gradient echo images were acquired and analyzed using our software based on fuzzy cluster analysis (EvIdent). Following the injection of 50 microl of formalin (5%) into the forepaw we observed a regional increase in signal intensity in the MR images in all animals. Anterior cingulate cortex, frontal cortex and sensory-motor cortex were some of the regions that activated frequently and often bilaterally. Surprisingly, activation appeared sequentially, often occurring first in either the right or the left hemisphere with a separation of seconds to minutes between peak activations. Morphine pre-treatment (1 mg/kg, i. v.) delayed and/or reduced the intensity of the activation resulting in a decrease in the overall response. Following episodes of intense electrical stimulation, produced by two brief stimulations (15 V, 0. 3 ms, 3 Hz) of the forepaw, activation was observed consistently in the sensory-motor cortex contralateral to the stimulation. Activation also occurred frequently in the anterior cingulate cortex, ipsilateral sensory-motor cortex and frontal cortical regions. All these regions of activation were markedly reduced during nitrous oxide inhalation. Treatment with morphine resulted in an inhibition of the activation response to electrical stimulation in most regions except for sensory-motor cortex. Thus, electrical and chemical noxious stimuli activated regions that are known to be involved in the central processing of pain and morphine modified the activation observed. fMRI combined with appropriate exploratory data analysis tools could provide an effective new tool with which to study novel analgesics and their effects on the CNS processing of pain in animal models.

A New Scenario for Negative Functional Magnetic Resonance Imaging Signals: Endogenous Neurotransmission

“…This hypothesis could explain the difficulty of finding nociception-induced hemodynamic responses in the CPu in both humans and rodents (Casey, 1999;Tuor et al, 2000;Chang and Shyu, 2001;Farrell et al, 2005;Lowe et al, 2007), and a recent report of negative BOLD responses in the CPu induced by intense electrical stimulation to the rat forepaw (Zhao et al, 2008a). Moreover, consistent with our findings, Morrow et al reported that CBF was reduced during the early phase of formalin-induced pain (Morrow et al, 1998).…”

“…The noxious 60 V electrical stimulation of the rat forepaw with a pair of needle electrodes was quantified using a compound ammeter, which showed that the delivered current was ϳ15 mA. This current level is known to activate A␦ and C-fibers and induce nociception (Tuor et al, 2000;Chang and Shyu, 2001;Liu et al, 2004;Zhao et al, 2008b).…”

Hyperpolarized Xenon Brain MRI

“…Conversely, hyperpolarized 129 Xe MRI showed patterns of brain activation consistent with those obtained using 1 H fMRI, using only a single set of images (one baseline and one post stimulus image) obtained from six animals. The magnitude of the signal difference between baseline and stimulus conditions for hyperpolarized 129 Xe (13-28%) was comparable to differences typically obtained with conventional BOLD fMRI (2 to 29%) (Bock et al, 1998;Silva et al, 1999;Mandeville et al, 1999;Tuor et al, 2000) using a rat forepaw activation paradigm.…”

Functional imaging of the rat cervical spinal cord

“…fMRI experiments using electrical stimulation in rats have repeatedly shown activations in the sensory motor cortex (1-3) and regions of the brain associated with processing of painful stimulation, such as the anterior cingulate (1). We wish to show that spinal fMRI can be used to assess electrical stimulation of the forepaw as well as capsaicin-induced pain in an anesthetized animal.…”

“…THE OCCURRENCE OF BLOOD OXYGEN-LEVEL dependent (BOLD) contrast changes in the brain is well established (1)(2)(3)(4)(5)(6). Recently, the extension of functional magnetic resonance imaging (fMRI) from the brain to the spinal cord has been demonstrated (7)(8)(9)(10)(11)(12)(13).…”