scholarly journals Peripheral and central hyperexcitability: Differential signs and symptoms in persistent pain

1997 ◽  
Vol 20 (3) ◽  
pp. 404-419 ◽  
Author(s):  
Terence J. Coderre ◽  
Joel Katz
Keyword(s):  
Neuropathic Pain ◽  
Postoperative Pain ◽  
Experimental Evidence ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Signs And Symptoms ◽  
Persistent Pain ◽  
Dorsal Horn Neurons ◽  
Target Article

This target article examines the clinical and experimental evidence for a role of peripheral and central hyperexcitability in persistent pain in four key areas: cutaneous hyperalgesia, referred pain, neuropathic pain, and postoperative pain. Each suggests that persistent pain depends not only on central sensitization, but also on inputs from damaged peripheral tissue. It is instructive to think of central sensitization as comprised of both an initial central sensitization and an ongoing central sensitization driven by inputs from peripheral sources. Each of these factors, initial sensitization, ongoing central sensitization, and inputs from peripheral sources, contributes to the net activity in dorsal horn neurons and thus influences the expression of persistent pain or hyperalgesia. Since each factor, peripheral inputs and central sensitization (initial or ongoing), can contribute to both the initiation and maintenance of persistent pain, therapies should target both peripheral and central sources of pathology.

scholarly journals Dorsal Horn α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptor Trafficking in Inflammatory Pain

2010 ◽  
Vol 112 (5) ◽  
pp. 1259-1265 ◽  
Author(s):  
Yuan-Xiang Tao ◽  
David S. Warner
Keyword(s):  
Dorsal Horn ◽  
Aspartic Acid ◽  
Central Sensitization ◽  
Inflammatory Pain ◽  
Persistent Pain ◽  
Receptor Trafficking ◽  
Current Evidence ◽  
Receptor Subunit ◽  
Acid Receptor ◽  
Dorsal Horn Neurons

Activation of synaptic N-methyl-D-aspartic acid receptor and its intracellular downstream signals in dorsal horn neurons of spinal cord contribute to central sensitization, a mechanism that underlies the development and maintenance of pain hypersensitivity in persistent pain. However, the molecular process of this event is not understood completely. Recently, new studies suggest that peripheral inflammatory insults drive changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit trafficking via N-methyl-D-aspartic acid receptor-triggered activation of protein kinases in dorsal horn and raise the possibility that such changes might contribute to central sensitization in persistent pain. This review presents current evidence regarding the changes that occur in the trafficking of dorsal horn alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits GluR1 and GluR2 under persistent inflammatory pain conditions and discusses the potential mechanisms by which such changes participate in the development and maintenance of inflammatory pain.

Sirtuin 1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons

Pain ◽  
2019 ◽  
Vol 160 (5) ◽  
pp. 1082-1092 ◽  
Author(s):  
Zongqin Zhang ◽  
Xiaobao Ding ◽  
Zhiwei Zhou ◽  
Zhuang Qiu ◽  
Naihao Shi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Synaptic Plasticity ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Sirtuin 1 ◽  
Diabetic Neuropathic Pain ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

Multiple Firing Patterns in Deep Dorsal Horn Neurons of the Spinal Cord: Computational Analysis of Mechanisms and Functional Implications

2010 ◽  
Vol 104 (4) ◽  
pp. 1978-1996 ◽  
Author(s):  
Yann Le Franc ◽  
Gwendal Le Masson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Information Transfer ◽  
Network Effects ◽  
Neuronal Response ◽  
Sensory Information ◽  
Firing Patterns ◽  
Dorsal Horn Neurons ◽  
The Impact

Deep dorsal horn relay neurons (dDHNs) of the spinal cord are known to exhibit multiple firing patterns under the control of local metabotropic neuromodulation: tonic firing, plateau potential, and spontaneous oscillations. This work investigates the role of interactions between voltage-gated channels and the occurrence of different firing patterns and then correlates these two phenomena with their functional role in sensory information processing. We designed a conductance-based model using the NEURON software package, which successfully reproduced the classical features of plateau in dDHNs, including a wind-up of the neuronal response after repetitive stimulation. This modeling approach allowed us to systematically test the impact of conductance interactions on the firing patterns. We found that the expression of multiple firing patterns can be reproduced by changes in the balance between two currents (L-type calcium and potassium inward rectifier conductances). By investigating a possible generalization of the firing state switch, we found that the switch can also occur by varying the balance of any hyperpolarizing and depolarizing conductances. This result extends the control of the firing switch to neuromodulators or to network effects such as synaptic inhibition. We observed that the switch between the different firing patterns occurs as a continuous function in the model, revealing a particular intermediate state called the accelerating mode. To characterize the functional effect of a firing switch on information transfer, we used correlation analysis between a model of peripheral nociceptive afference and the dDHN model. The simulation results indicate that the accelerating mode was the optimal firing state for information transfer.

scholarly journals Activated Microglia Contribute to Convergent Nociceptive Inputs to Spinal Dorsal Horn Neurons and the Development of Neuropathic Pain

2015 ◽  
Vol 40 (5) ◽  
pp. 1000-1012 ◽  
Author(s):  
Yuya Yamamoto ◽  
Ryuji Terayama ◽  
Noriko Kishimoto ◽  
Kotaro Maruhama ◽  
Masahide Mizutani ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Activated Microglia ◽  
Dorsal Horn Neurons ◽  
Spinal Dorsal ◽  
Spinal Dorsal Horn Neurons

The original description of central sensitization

2018 ◽  
Author(s):  
Sheila Black
Keyword(s):  
Amino Acids ◽  
Dorsal Horn ◽  
Central Sensitization ◽  
Excitatory Amino Acids ◽  
Formalin Test ◽  
Tissue Injury ◽  
Original Description ◽  
Nociceptive Responses ◽  
Landmark Study

The landmark study discussed in this chapter is ‘The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury’, published by Coderre and Melzack in 1992. Previous studies in this field implicate a contribution of excitatory amino acids (EAAs), specifically l-glutamate and l-aspartate, to injury-induced sensitization of nociceptive responses in the dorsal horn of the spinal cord. Repetitive stimulation of primary afferent fibres demonstrated that l-glutamate and NMDA can produce ‘wind-up’ of neuronal dorsal horn activity, and this is blocked by application of NMDA antagonists. This study uses the formalin test as a behavioural model to investigate the mechanisms underlying central sensitization and the role of EAAs, NMDA, their receptors, and their antagonists in this process.

scholarly journals Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability

2020 ◽  
Vol 6 (8) ◽  
pp. eaax4568 ◽  
Author(s):  
Sascha R. A. Alles ◽  
Filipe Nascimento ◽  
Rafael Luján ◽  
Ana P. Luiz ◽  
Queensta Millet ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Dorsal Horn Neuron ◽  
Mutant Mice ◽  
Afferent Neuron ◽  
Null Mutant ◽  
Dorsal Horn Neurons ◽  
Afferent Nerves ◽  
Horn Neuron ◽  
Null Mutant Mice

Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse. Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an expression pattern that would not be predicted by transcriptomic analysis.

Role of cervical neurons in propriospinal inhibition of thoracic dorsal horn neurons

1992 ◽  
Vol 599 (2) ◽  
pp. 302-308 ◽  
Author(s):  
Lawrence R. Poree ◽  
Lawrence P. Schramm
Keyword(s):  
Dorsal Horn ◽  
Dorsal Horn Neurons
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