Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin

@article{Suzuki2005SpinalsupraspinalSC,
  title={Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin},
  author={Rie Suzuki and Wahida Rahman and Lars J{\o}rgen Rygh and Mark Webber and Stephen P Hunt and Anthony Henry Dickenson},
  journal={Pain},
  year={2005},
  volume={117},
  pages={292-303}
}

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References

SHOWING 1-10 OF 65 REFERENCES
Upregulation of Dorsal Root Ganglion α2δ Calcium Channel Subunit and Its Correlation with Allodynia in Spinal Nerve-Injured Rats
TLDR
Using a rat neuropathic pain model in which gabapentin-sensitive tactile allodynia develops after tight ligation of the left fifth and sixth lumbar spinal nerves, a >17-fold, time-dependent increase in α2δ subunit expression in DRGs ipsilateral to the nerve injury is found, suggesting that DRG α2 δ regulation may play an unique role in neuroplasticity after peripheral nerve injury.
Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways
TLDR
It is concluded that NK1-positive spinal projection neurons, activated by primary afferent input, project to higher brain areas that control spinal excitability—and therefore pain sensitivity—primarily through descending pathways from the brainstem.
Spinal Neurons that Possess the Substance P Receptor Are Required for the Development of Central Sensitization
TLDR
Results demonstrate that SPR-expressing neurons located in the dorsal horn are a pivotal component of the spinal circuits involved in triggering central sensitization and hyperalgesia and it appears that this relatively small population of neurons can regulate the physiological properties of other nociceptive neurons and drive central sensitized.
Transmission of chronic nociception by spinal neurons expressing the substance P receptor.
TLDR
It is suggested that the small population of SPR-expressing neurons in the dorsal horn of the spinal cord plays a pivotal role in the generation and maintenance of chronic neuropathic and inflammatory pain.
Supraspinal contributions to hyperalgesia.
  • M. UrbanG. Gebhart
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
TLDR
Data suggest a prominent role for the RVM in mediating the sensitization of spinal neurons and development of secondary hyperalgesia, and results to date suggest that peripheral injury and persistent input engage spinobulbospinal mechanisms that may be the prepotent contributors to central sensitization and development.
Role of descending noradrenergic system and spinal α2‐adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse
TLDR
It was concluded that the antihyperalgesic and antiallodynic effects of gabapentin are mediated substantially by the descending noradrenergic system, resulting in the activation of spinal α2‐adrenerential receptors.
Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor.
Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein
...
...