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Page 6 of 8 Toyoda. Neuroimmunol Neuroinflammation 2018;5:40 I http://dx.doi.org/10.20517/2347-8659.2018.48

CONCLUSION
Peripheral nerve injuries and peripheral inflammation can cause extensive changes in pain processing
in the central nervous system. Many in vitro and in vivo studies have proved compelling evidence that
changes in both presynaptic and postsynaptic function are responsible for chronic pain. It is believed that
the key presynaptic and postsynaptic events in chronic pain in the central nervous system are synaptic
plasticity triggered by peripheral nerve injury and ongoing unusual sensory inputs afterwards. Therefore,
understanding of molecular and cellular mechanisms underlying the pain-induced synaptic plasticity
will provide new therapeutic targets for treating persistent pain in patients. At present, little is understood
about molecular mechanisms underlying presynaptic changes in chronic pain state, compared to those
underlying postsynaptic changes. Thus, it is necessary to further elucidate the cellular and molecular
mechanisms underlying presynaptic changes in the ACC of chronic pain mice. Treatment of chronic pain is
difficult because current available drugs for chronic pain induce unwanted side effects or supply insufficient
analgesia. Thus, studies focusing on the molecular mechanisms of presynaptic changes in the ACC of
chronic pain mice could lead to the development of effective novel analgesics on treating chronic pain.
Although it has been reported that pre-LTP in the ACC synapses is involved in pain-triggered anxiety and
fear [64,65] , the molecular and cellular mechanisms for the pre-LTP are not well understood. Understanding of
these mechanisms for pre-LTP in the ACC synapses will help to develop new therapeutic strategies for pain-
triggered anxiety and fear.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Number
17K08538.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2018.

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