Dr Sandkühler raises several relevant and interesting points regarding our review
on activity-dependent central sensitization and synaptic plasticity, and we are happy
to clarify our approach to, and understanding of, synaptic plasticity in the dorsal
horn, particularly the relationship between central sensitization and long-term potentiation
(LTP). The definition of LTP needs to be addressed, we believe, in the context of
the type of preparation (in vivo or in vitro), nature of the neurons (cerebellum,
neocortex, hippocampus, dorsal horn), the synaptic changes that occur (homo- or heterosynaptic,
pre- or postsynaptic), duration of changes (short term or persistent), molecular mechanisms
(signal transduction pathways engaged, transcription independent or dependent), and
the biological function of the circuits involved (learning, memory, or pain). For
our review,
17
we focused on the relationship between the different forms of activity-dependent
synaptic plasticity reported in the dorsal horn of the spinal cord, including those
that have been called LTP, and central sensitization. We thought it was particularly
relevant to address the phenomenon of central sensitization as a defense mechanism
specific to nociception, one that contributes to maintaining the integrity of the
organism by producing pain hypersensitivity following a conditioning nociceptive afferent
barrage, and, in this way, protecting an organism from further damage. This is an
evolutionary conserved process, with prominent central sensitization-like behavior
in Aplysia and other invertebrates;
2
,
30
and while it shares general mechanistic aspects with several forms of synaptic plasticity
in other systems, there are also, we argue, some important differences that make central
sensitization unique. At a conceptual level, for example, we believe that there is
a major difference between the input-specific synaptic potentiation that constitutes
classic LTP in cortical neurons
4
,
20
,
21
and the more generalized heightened excitability in nociceptive pathways that underlies
central sensitization.
26
,
29
Memory, which is widely considered dependent on hippocampal LTP,
4
,
19
,
20
,
21
,
23
is a convergent neural operation where the storage of defined information is the
consequence of coincident temporal and spatial association between specific stimuli.
In contrast, central sensitization represents a divergent neural operation, one where
a conditioning nociceptive input triggers diffuse changes such that other unstimulated
synaptic inputs can now generate pain. For example, nociceptive stimulation of deep
tissue, like muscle, results in an enlargement and reduction in threshold of the cutaneous
receptive field of dorsal horn neurons, to an extent and duration that is even greater
than when a nociceptive input is generated from the skin.
28
If central sensitization were entirely maintained by LTP, it would not have this
fundamental feature, which characterizes it.To read this article in full you will need to make a payment
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- Central Sensitization Versus Synaptic Long-Term Potentiation (LTP): A Critical CommentThe Journal of PainVol. 11Issue 8
- PreviewI read with interest the chapter, “Activity-Dependent Central Sensitization and Synaptic Plasticity,” in the recent review article by Latrémolière and Woolf11 in The Journal of Pain. I noticed a number of issues in that chapter which deserve some discussion. These include the concept of synaptic long-term potentiation in pain pathways and its relation to the more general phrase “central sensitization.”
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