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Toyoda. Neuroimmunol Neuroinflammation 2018;5:40 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.48 Neuroinflammation

Review Open Access

Presynaptic mechanisms at prefrontal synapses
involved in persistent pain

Hiroki Toyoda

Department of Oral Physiology, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan.
Correspondence to: Hiroki Toyoda, Department of Oral Physiology, Osaka University Graduate School of Dentistry, Osaka 565-0871,
Japan. E-mail: toyoda@dent.osaka-u.ac.jp
How to cite this article: Toyoda H. Presynaptic mechanisms at prefrontal synapses involved in persistent pain. Neuroimmunol
Neuroinflammation 2018;5:40. http://dx.doi.org/10.20517/2347-8659.2018.48

Received: 18 Aug 2018 First Decision: 5 Sep 2018 Revised: 9 Sep 2018 Accepted: 10 Sep 2018 Published: 29 Sep 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

ABSTRACT
The cumulative evidence from animal and human studies revealed that the anterior cingulate cortex (ACC)
plays essential roles in pain sensation and persistent pain. It has been evident in the ACC synapses of animals
that changes in both the presynaptic and postsynaptic function are caused by peripheral nerve injury. Thus far,
postsynaptic changes in the ACC following nerve injury have been primarily studied to understand the mechanisms
of chronic pain. In recent years, studies focusing on the presynaptic mechanisms in chronic pain have been
progressively increased. In this review, I will discuss molecular mechanisms associated with chronic pain and
presynaptic form of long-term potentiation. I will also discuss evidence for presynaptic changes in the ACC caused
by disease-related pain.

Keywords: Presynaptic mechanism, chronic pain, anterior cingulate cortex

INTRODUCTION
The anterior cingulate cortex (ACC) plays critical roles in the processing of pain information in patients
[1-8]
and is involved in behavioral responses to tissue damages that cause pain in animals . The ACC also
contributes to various cognitive processes including decision-making, attention and working memory [9,10] .
Humans and animals with persistent pain displayed poor performance in decision-making cognitive
tasks [11-13] . Therefore, the understanding of the cellular and molecular mechanisms of chronic pain is very
important in ameliorating the cognitive impairments.

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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