Limits...
Neuronal mechanism for neuropathic pain.

Zhuo M - Mol Pain (2007)

Bottom Line: Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking.I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we may have to wait for a long time before we fully understand how brain encode, store, and retrieve painful information after the injury.I propose that neuropathic pain as a major brain disease, rather being a clinic problem due to peripheral injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the study of Pain, University of Toronto, Toronto, Ontario, Canada. min.zhuo@utoronto.ca

ABSTRACT
Among different forms of persistent pain, neuropathic pain presents as a most difficult task for basic researchers and clinicians. Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking. Here, I will review the basic neuronal mechanisms that maybe involved in neuropathic pain. I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we may have to wait for a long time before we fully understand how brain encode, store, and retrieve painful information after the injury. I propose that neuropathic pain as a major brain disease, rather being a clinic problem due to peripheral injury.

Show MeSH

Related in: MedlinePlus

Long-term potentiation of sensory excitatory synapses in adult mouse ACC. A. Current-clamp recordings to identify pyramidal neurons (upper) and interneurons (bottom) by current injections of -100, 0, and 100 pA. A labeled pyramid-like neuron was shown on the top right. RP: resting membrane potential. B. LTP was induced in pyramidal neurons (n = 15) in adult ACC by the pairing training protocol (indicated by an arrow). The insets show averages of 6 EPSCs 5 min before and 25 min after the pairing training (arrow). The dashed line indicates the mean basal synaptic responses. C. An example showing the long-lasting synaptic potentiation. Pairing training is indicated by an arrow. D. Basic synaptic transmission showing no change during recording without applying pairing training. The insets show averages of 6 EPSCs at the time points of 5 (pre) and 35 (post) min during the recording [Modified from 15].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1904186&req=5

Figure 3: Long-term potentiation of sensory excitatory synapses in adult mouse ACC. A. Current-clamp recordings to identify pyramidal neurons (upper) and interneurons (bottom) by current injections of -100, 0, and 100 pA. A labeled pyramid-like neuron was shown on the top right. RP: resting membrane potential. B. LTP was induced in pyramidal neurons (n = 15) in adult ACC by the pairing training protocol (indicated by an arrow). The insets show averages of 6 EPSCs 5 min before and 25 min after the pairing training (arrow). The dashed line indicates the mean basal synaptic responses. C. An example showing the long-lasting synaptic potentiation. Pairing training is indicated by an arrow. D. Basic synaptic transmission showing no change during recording without applying pairing training. The insets show averages of 6 EPSCs at the time points of 5 (pre) and 35 (post) min during the recording [Modified from 15].

Mentions: In the ACC, the induction of LTP by different protocols is mostly NMDA receptor dependent. NMDA receptor containing NR2A or NR2B subunits contribute to most of NMDA receptor currents [15]. Bath application of a NR2A antagonist NVP-AAM077 and NR2B antagonist ifenprodil/Ro compounds produce almost completely blockade of NMDA receptor mediated EPSCs. Application of NR2A or NR2B antagonist reduces LTP, without complete abolishment of LTP. LTP is only abolished after the co-application of both inhibitors [15]. It is noted that LTP induced by spike-timing protocol seems to more sensitive to NMDA NR2B blockade as compared with effects on LTP induced by pairing training protocol [15]. In addition to NMDA receptors, L-type voltage gated calcium channels (L-VDCCs) are required for inducing LTP [46] when LTP is induced by theta-burst stimulation (TBS) in field recording conditions. Therefore, it is likely that ACC LTP induced by different protocols may mimic different physiological/pathological conditions by distinct signaling pathways (see fig 3).


Neuronal mechanism for neuropathic pain.

Zhuo M - Mol Pain (2007)

Long-term potentiation of sensory excitatory synapses in adult mouse ACC. A. Current-clamp recordings to identify pyramidal neurons (upper) and interneurons (bottom) by current injections of -100, 0, and 100 pA. A labeled pyramid-like neuron was shown on the top right. RP: resting membrane potential. B. LTP was induced in pyramidal neurons (n = 15) in adult ACC by the pairing training protocol (indicated by an arrow). The insets show averages of 6 EPSCs 5 min before and 25 min after the pairing training (arrow). The dashed line indicates the mean basal synaptic responses. C. An example showing the long-lasting synaptic potentiation. Pairing training is indicated by an arrow. D. Basic synaptic transmission showing no change during recording without applying pairing training. The insets show averages of 6 EPSCs at the time points of 5 (pre) and 35 (post) min during the recording [Modified from 15].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1904186&req=5

Figure 3: Long-term potentiation of sensory excitatory synapses in adult mouse ACC. A. Current-clamp recordings to identify pyramidal neurons (upper) and interneurons (bottom) by current injections of -100, 0, and 100 pA. A labeled pyramid-like neuron was shown on the top right. RP: resting membrane potential. B. LTP was induced in pyramidal neurons (n = 15) in adult ACC by the pairing training protocol (indicated by an arrow). The insets show averages of 6 EPSCs 5 min before and 25 min after the pairing training (arrow). The dashed line indicates the mean basal synaptic responses. C. An example showing the long-lasting synaptic potentiation. Pairing training is indicated by an arrow. D. Basic synaptic transmission showing no change during recording without applying pairing training. The insets show averages of 6 EPSCs at the time points of 5 (pre) and 35 (post) min during the recording [Modified from 15].
Mentions: In the ACC, the induction of LTP by different protocols is mostly NMDA receptor dependent. NMDA receptor containing NR2A or NR2B subunits contribute to most of NMDA receptor currents [15]. Bath application of a NR2A antagonist NVP-AAM077 and NR2B antagonist ifenprodil/Ro compounds produce almost completely blockade of NMDA receptor mediated EPSCs. Application of NR2A or NR2B antagonist reduces LTP, without complete abolishment of LTP. LTP is only abolished after the co-application of both inhibitors [15]. It is noted that LTP induced by spike-timing protocol seems to more sensitive to NMDA NR2B blockade as compared with effects on LTP induced by pairing training protocol [15]. In addition to NMDA receptors, L-type voltage gated calcium channels (L-VDCCs) are required for inducing LTP [46] when LTP is induced by theta-burst stimulation (TBS) in field recording conditions. Therefore, it is likely that ACC LTP induced by different protocols may mimic different physiological/pathological conditions by distinct signaling pathways (see fig 3).

Bottom Line: Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking.I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we may have to wait for a long time before we fully understand how brain encode, store, and retrieve painful information after the injury.I propose that neuropathic pain as a major brain disease, rather being a clinic problem due to peripheral injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Faculty of Medicine, University of Toronto Centre for the study of Pain, University of Toronto, Toronto, Ontario, Canada. min.zhuo@utoronto.ca

ABSTRACT
Among different forms of persistent pain, neuropathic pain presents as a most difficult task for basic researchers and clinicians. Despite recent rapid development of neuroscience and modern techniques related to drug discovery, effective drugs based on clear basic mechanisms are still lacking. Here, I will review the basic neuronal mechanisms that maybe involved in neuropathic pain. I will present the problem of neuropathic pain as a rather difficult task for neuroscientists, and we may have to wait for a long time before we fully understand how brain encode, store, and retrieve painful information after the injury. I propose that neuropathic pain as a major brain disease, rather being a clinic problem due to peripheral injury.

Show MeSH
Related in: MedlinePlus