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First published online on December 14, 2001.
 Copyright © 2001 by The Physiological Society
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Received August 8, 2001
Accepted after revision October 24, 2001

Hypocretin-2 (OREXIN-B) modulation of superficial dorsal horn activity in rat

Timothy J. Grudt1, Anthony N. van den Pol2, and Edward R. Perl1*

1 Department of Cell and Molecular Physiology, University of North Carolina - Chapel Hill, Chapel Hill, NC 27599, USA
2 Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA

* To whom correspondence should be addressed. E-mail: erp{at}med.unc.edu.

The hypothalamic peptides hypocretin-1 (orexin A) and hypocretin-2 (Hcrt-2; orexin B) are important in modulating behaviours demanding arousal, including sleep and appetite. Fibres containing hypocretin project from the hypothalamus to the superficial dorsal horn (SDH) of the spinal cord (laminae I and II); however, the effects produced by hypocretins on SDH neurones are unknown. To study the action of Hcrt-2 on individual SDH neurones, tight-seal, whole-cell recordings were made with biocytin-filled electrodes from rat lumbar spinal cord slices. In 19 of 63 neurones, Hcrt-2 (30 nM to 1 µM) evoked an inward (excitatory) current accompanied by an increase in baseline noise. The inward current and noise were unaffected by TTX but were blocked by the P2X purinergic receptor antagonist suramin (300-500 µM). Hcrt-2 (30 nM to 1 µM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in the majority of neurones. The sIPSC increase was blocked by strychnine (1 µM) and by TTX (1 µM), suggesting that the increased sIPSC frequency was glycine and action potential dependent. Hcrt-2 increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in a few neurones but had no effect on dorsal root-evoked EPSCs in these or in other neurones. Neurones located in outer lamina II, particularly radial and vertical cells, were most likely to respond to Hcrt-2. We conclude that Hcrt-2 has excitatory effects on certain SDH neurones, some of which exert inhibitory influences on other cells of the region, consistent with the perspective that hypocretin has a role in orchestrating reactions related to arousal, including nociception, pain and temperature sense.




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