Abstract

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.

Highlights

  • Pain and pleasure are two key factors in most parts of daily life

  • This form of potentiation is sensitive to inhibition of protein synthesis (Chen et al 2014, unpublished data; see [23] for the insular cortex), indicating that protein synthesis-dependent late-phase LTP (L-LTP) exists in the anterior cingulate cortex (ACC)

  • In cAMP response element-binding protein (CREB) overexpression mice, the increases of fragile X mental retardation protein (FMRP) triggered by activation of metabotropic glutamate receptors are significantly enhanced [6], whereas in FMRP knockout mice, activation of CREB is similar to wild-type mice. These results suggest that FMRP is likely to act downstream from CREB in ACC neurons

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Summary

Introduction

Pain and pleasure are two key factors in most parts of daily life. While we work to survive in a competitive society, and seek different forms of pleasure, we try to avoid pain when it is possible. The discovery of analgesic drugs such as opioids has greatly helped doctors to reduce the suffering of patients during and after surgery. While these drugs are effective for controlling pain which is short lasting (called acute pain), it is ineffective in controlling chronic pain. Recent integrative neuroscience studies have found that chronic pain and acute pain operate through different central mechanisms [1]. Inhibitors that reduce pain transmission do not prevent the induction of chronic pain-related synaptic potentiation (called long-term potentiation, LTP), and inhibitors that abolish potentiation do not affect acute or physiological pain [1,2]. The mechanisms of the induction and expression of pain-related LTP potentially provide new therapeutic targets for controlling chronic pain in patients. License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited

Pain and cortex
Pain perception is probably processed by a few key cortical areas
Pain-related spinal long-term potentiation and heterosynaptic facilitation
Pain-related cortical synapses are plastic
Different forms of anterior cingulate cortex long-term potentiation
Gene expression and synaptic potentiation
15. Conclusion and future directions
12. Li XY et al 2010 Alleviating neuropathic pain
Findings
29. Wang H et al 2011 Identification of an adenylyl
Full Text
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