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Int J Physiol Pathophysiol Pharmacol 2013;5(1):43-51

Original Article
Alteration of neuronal activity after digit amputation in rat anterior cingulate cortex

Jianguo Li, Minfan Wu, Min Zhuo, Zao C Xu

Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Physiology,
Faculty of Medicine and Centre for the Study of Pain, University of Toronto, Toronto, Ontario, Canada M5S 1A8; Current address:
Department of Physiology, Shanxi Medical University, China; Current address: Department of Physiology, Shenyang Medical College,

Received January 25, 2013; Accepted February 20, 2013; Epub March 8, 2013; Published March 18, 2013

Abstract: Phantom limb pain is experienced by nearly 50 - 80% of the patients following limb amputation. The anterior cingulate cortex
(ACC) is a part of the limbic system that is an essential component in mediating the affective and emotional component of pain
responses. To explore the role of ACC in the phantom limb pain, we recorded evoked excitatory postsynaptic potentials (EPSPs),
cortical network activity and electrophysiological properties of pyramid neurons in adult rat ACC before and after a third hind paw digit
amputation using in vivo intracellular or extracellular recording and staining techniques. The recorded neurons were morphologically
identified as pyramidal neurons in the ACC region. The spontaneous activity of ACC neurons significantly reduced with a more
percentage of down state after amputation, this is correlated with a decrease in spontaneous spikes in medial thalamus. However, the
amplitude of the evoked EPSPs was increased significantly shortly after amputation and lasted for up to 7 days. This potentiation is
associated with an increase of paired-pulse facilitation (PPF), suggesting the involvement of presynaptic component in this process.
No significant difference in membrane properties was observed after amputation. On the other hand, administration of Complete
Freund’s Adjuvant (CFA) into the hind paw, a model of inflammatory pain, induced the potentiation of EPSPs in ACC neurons at 7 days
after injection. These results demonstrate that digit amputation induced a long-lasting potentiation of synaptic transmission and
decrease of cortical network activity in ACC in rats, which might contribute to the phantom limb pain. (IJPPP1301005)

Keywords: Phantom pain, cortex, pyramidal neurons, EPSPs, in vivo, intracellular recording

Address correspondence to: Dr. Zao C Xu, Department of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill
Drive, Indianapolis IN 46202, USA. Tel: 317-274-0547; Fax: 317-278-2040; E-mail: zcxu@iupui.edu