Highlights
- •Peripheral nociception induced gain of spatial and temporal plasticity in the primary somatosensory cortex.
- •Excitatory transmission was enhanced with both presynaptic and postsynaptic ingredients.
- •Inhibitory transmission was reduced with loss of gamma-amino butyric acid-A function.
- •The excitatory/inhibitory imbalance may contribute to the plastic changes in the primary somatosensory cortex.
Abstract
There is substantial evidence supporting the notion that the primary somatosensory
(S1) cortex is an important structure involved in the perceptional component of pain.
However, investigations have mainly focused on other pain-related formations, and
few reports have been provided to investigate the synaptic plasticity in the S1 cortex
in response to persistent pain. In the present study, we report that bee venom (BV)
injection triggered an imbalance between excitatory and inhibitory synaptic transmission
in the S1 cortex in rats. Using a multi-electrode array recording, we found that BV-induced
persistent inflammatory pain led to temporal and spatial enhancement of synaptic plasticity.
Moreover, slice patch clamp recordings on identified pyramidal neurons demonstrated
that BV injection increased presynaptic and postsynaptic transmission in excitatory
synapses and decreased postsynaptic transmission in inhibitory synapses in the layer
II/III neurons within the S1 cortex. In immunohistochemistry and Western blot sections,
the distribution and expression of total AMPA receptor subunits and gamma-amino butyric
acid-A (GABAA) were unaffected, although the membrane fractions of GluR2 and GABAA were decreased, and their cytosolic fractions were increased in contrast. The change
of GluR1 was opposite to that of GluR2, and GluR3 did not change significantly. Our
studies, therefore, provide direct evidence for both presynaptic and postsynaptic
changes in synapses within the S1 cortex in persistent nociception, which are probably
related to the membrane trafficking of GluR1, GluR2, and GABAA.
Perspective: Increased synaptic plasticity was detected in S1 after peripheral nociception,
with enhanced excitatory and decreased inhibitory synaptic transmissions. Increased
GluR1, and decreased GABAAα1 and GluR2 membrane trafficking were detected. Therefore,
the disrupted excitatory/inhibitory balance in transmissions is involved in nociception
processing, and S1 can be a potential antinociceptive site.
Key words
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References
- Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: Are they effective or relevant?.Exp Neurol. 2007; 204: 1-13
- The concept of long term potentiation of transmission at synapses.Prog Neurobiol. 2000; 60: 109-137
- Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neurones.J Physiol. 2005; 564: 907-921
- A synaptic model of memory: Long-term potentiation in the hippocampus.Nature. 1993; 361: 31-39
- Regulation of hippocampal transmitter release during development and long-term potentiation.Science. 1995; 269: 1730-1734
- Forebrain mechanisms of nociception and pain: Analysis through imaging.Proc Natl Acad Sci U S A. 1999; 96: 7668-7674
- Spatiotemporal characteristics of pain-associated neuronal activities in primary somatosensory cortex induced by peripheral persistent nociception.Neurosci Lett. 2008; 448: 134-138
- Secondary heat, but not mechanical, hyperalgesia induced by subcutaneous injection of bee venom in the conscious rat: Effect of systemic MK-801, a non-competitive NMDA receptor antagonist.Eur J Pain. 2000; 4: 389-401
- The nociceptive and anti-nociceptive effects of bee venom injection and therapy: A double-edged sword.Prog Neurobiol. 2010; 92: 151-183
- Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-range neurons induced by subcutaneous bee venom injection in the cat.Brain Res. 1999; 844: 98-105
- The contribution of spinal neuronal changes to development of prolonged, tonic nociceptive responses of the cat induced by subcutaneous bee venom injection.Eur J Pain. 1998; 2: 359-376
- Regulatory mechanisms of AMPA receptors in synaptic plasticity.Nat Rev Neurosci. 2007; 8: 101-113
- Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms.Neuroimage. 2007; 37: S71-S79
- Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.PloS One. 2014; 9: e95491
- Enhanced excitatory and reduced inhibitory synaptic transmission contribute to persistent pain-induced neuronal hyper-responsiveness in anterior cingulate cortex.Neuroscience. 2010; 171: 1314-1325
- AMPA receptor biogenesis and trafficking.Curr Opin Neurobiol. 2007; 17: 289-297
- Critical role of calcitonin gene-related peptide 1 receptors in the amygdala in synaptic plasticity and pain behavior.J Neurosci. 2005; 25: 10717-10728
- The molecular biology of memory storage: A dialogue between genes and synapses.Science. 2001; 294: 1030-1038
- During pain-avoidance neurons activated in the macaque anterior cingulate and caudate.Neurosci Lett. 2000; 283: 17-20
- Altered pain-related behaviors and spinal neuronal responses produced by s.c injection of melittin in rats.Neuroscience. 2004; 126: 753-762
- Motor cortex stimulation for chronic pain: Systematic review and meta-analysis of the literature.Neurology. 2008; 70: 2329-2337
- Long-term potentiation of C-fiber-evoked potentials in the rat spinal dorsal horn is prevented by spinal N-methyl-D-aspartic acid receptor blockage.Neurosci Lett. 1995; 191: 43-46
- Long-term potentiation–a decade of progress?.Science. 1999; 285: 1870-1874
- Glutamate-induced long-term potentiation of the frequency of miniature synaptic currents in cultured hippocampal neurons.Nature. 1992; 357: 134-139
- AMPA receptor trafficking and synaptic plasticity.Annu Rev Neurosci. 2002; 25: 103-126
- From the gate to the neuromatrix.Pain. 1999; : S121-S126
- Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord.J Neurosci. 2002; 22: 6724-6731
- Bilateral activation of the trigeminothalamic tract by acute orofacial cutaneous and muscle pain in humans.Pain. 2010; 151: 384-393
- Contrasting properties of two forms of long-term potentiation in the hippocampus.Nature. 1995; 377: 115-118
- Synaptic plasticity at hippocampal mossy fibre synapses.Nat Rev Neurosci. 2005; 6: 863-876
- Role of spinal cord alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in complete Freund's adjuvant-induced inflammatory pain.Mol Pain. 2008; 4: 67
- The rat brain in stereotaxic coordinates.Elsevier Academic Press, San Diego, CA2005
- [Cortical representation of pain].Nervenarzt. 2004; 75: 962-969
- Induction of long-term potentiation at spinal synapses by noxious stimulation or nerve injury.Eur J Neurosci. 1998; 10: 2476-2480
- Neurophysiology and functional neuroimaging of the somatosensory system.J Clin Neurophysiol. 2000; 17: 537-538
- Separate, parallel sensory and hedonic pathways in the mammalian somatosensory system.Brain Res Bull. 2002; 58: 243-260
- The medial pain system: Neural representations of the motivational aspect of pain.Brain Res Bull. 2002; 59: 163-180
- Nociceptive neurons in area 24 of rabbit cingulate cortex.J Neurophysiol. 1992; 68: 1720-1732
- Cerebral processing of acute skin and muscle pain in humans.J Neurophysiol. 1997; 78: 450-460
- Multiple representations of pain in human cerebral cortex.Science. 1991; 251: 1355-1358
- Enhanced quantal release of excitatory transmitter in anterior cingulate cortex of adult mice with chronic pain.Mol Pain. 2009; 5: 4
- The cortical representation of pain.Pain. 1999; 79: 105-111
- Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning.Neuron. 2004; 41: 139-151
- The medial pain system, cingulate cortex, and parallel processing of nociceptive information.Prog Brain Res. 2000; 122: 223-235
- Neural circuits and temporal plasticity in hindlimb representation of rat primary somatosensory cortex: Revisited by multi-electrode array on brain slices.Neurosci Bull. 2010; 26: 175-187
- A rise in postsynaptic Ca2+ potentiates miniature excitatory postsynaptic currents and AMPA responses in hippocampal neurons.Neuron. 1994; 12: 127-138
- Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex.J Neurosci. 2008; 28: 7445-7453
- Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: Effects of modulatory receptor systems and excitatory amino acid antagonists.Pain. 1989; 37: 111-123
- Morphological and electrophysiological properties of ACCx nociceptive neurons in rats.Brain Res. 1996; 735: 83-92
- Imbalance between excitatory and inhibitory amino acids at spinal level is associated with maintenance of persistent pain-related behaviors.Pharmacol Res. 2009; 59: 290-299
- Lateralisation of nociceptive processing in the human brain: A functional magnetic resonance imaging study.Neuroimage. 2004; 23: 1068-1077
- Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn.J Neurosci. 2000; 20: 4922-4929
- Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain.J Neurosci. 2006; 26: 8923-8930
- Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: A multi-electrode array recording.Mol Pain. 2009; 5: 55
Article info
Publication history
Published online: February 08, 2019
Accepted:
November 12,
2018
Received in revised form:
August 4,
2018
Received:
January 31,
2018
Footnotes
Supported by the following funds: The National Basic Research (973) Program of China 2006CB500800, National Natural Science Foundation of China grants (30670692 and 30770668), the Natural Science Foundation of Shandong Province (ZR2015CQ015 and ZR2015HQ028), and the Growth Project of Military Medical Science and Technology Youth Training Program (16QNP063).
The authors have no conflicts of interest to declare.
Identification
Copyright
© 2019 by the American Pain Society
