Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors

Thaddeus S. Brink, Cholawat Pacharinsak, Sergey Khasabov, Al J Beitz, Donald A Simone

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The rostral ventro-medial medulla (RVM) is part of descending circuitry that modulates nociceptive processing at the level of the spinal cord. RVM output can facilitate pain transmission under certain conditions such as inflammation, and thereby contribute to hyperalgesia. Evidence suggests that substance P and activation of neurokinin-1 (NK-1) receptors in the RVM are involved in descending facilitation of nociception. We showed previously that injection of NK-1 receptor antagonists into the RVM attenuated mechanical and heat hyperalgesia produced by in-traplantar injection of capsaicin. Furthermore, intraplantar injection of capsaicin excited ON cells in the RVM and inhibited ongoing activity of OFF cells. In the present studies, we therefore examined changes in responses of RVM neurons to mechanical and heat stimuli after intraplantar injection of capsaicin and determined the role of NK-1 receptors by injecting a NK-1 receptor antagonist into the RVM prior to capsaicin. After capsaicin injection, excitatory responses of ON cells and inhibitory responses of OFF cells evoked by mechanical and heat stimuli applied to the injected, but not contralateral, paw were increased. Injection of the NK-1 antagonist L-733,060 did not alter evoked responses of ON or OFF cells but attenuated the capsaicin-evoked enhanced responses of ON cells to mechanical and heat stimuli with less of an effect on the enhanced inhibitory responses of OFF cells. These data support the notion that descending facilitation from RVM contributes to hyperalgesia and that NK-1 receptors, presumably located on ON cells, play an important role in initiating descending facilitation of nociceptive transmission.

Original languageEnglish (US)
Pages (from-to)1210-1221
Number of pages12
JournalJournal of neurophysiology
Volume107
Issue number4
DOIs
StatePublished - Feb 1 2012

Fingerprint

Neurokinin-1 Receptors
Capsaicin
Neurons
Injections
Hyperalgesia
Hot Temperature
Neurokinin-1 Receptor Antagonists
3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine
Nociception
Substance P
Spinal Cord
Inflammation
Pain

Keywords

  • Descending facilitation
  • Electrophysiology
  • Hyperalgesia
  • Nociception
  • Pain facilitation
  • Pain modulation
  • Raphe magnus
  • Substance p

Cite this

Differential modulation of neurons in the rostral ventromedial medulla by neurokinin-1 receptors. / Brink, Thaddeus S.; Pacharinsak, Cholawat; Khasabov, Sergey; Beitz, Al J; Simone, Donald A.

In: Journal of neurophysiology, Vol. 107, No. 4, 01.02.2012, p. 1210-1221.

Research output: Contribution to journalArticle

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