Thermal Nociception is Decreased by Hypocretin-1 and an Adenosine A1 Receptor Agonist Microinjected into the Pontine Reticular Formation of Sprague Dawley Rat

Sarah L. Watson, Christopher J. Watson, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Clinical and preclinical data concur that sleep disruption causes hyperalgesia, but the brain mechanisms through which sleep and pain interact remain poorly understood. Evidence that pontine components of the ascending reticular activating system modulate sleep and nociception encouraged the present study testing the hypothesis that hypocretin-1 (orexin-A) and an adenosine receptor agonist administered into the pontine reticular nucleus, oral part (PnO) each alter thermal nociception. Adult male rats (n = 23) were implanted with microinjection guide tubes aimed for the PnO. The PnO was microinjected with saline (control), hypocretin-1, the adenosine A1 receptor agonist N6-p-sulfophenyladenosine (SPA), the hypocretin receptor-1 antagonist N-(2-Methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl-urea (SB-334867), and hypocretin-1 plus SB-334867. As an index of antinociceptive behavior, the latency (in seconds) to paw withdrawal away from a thermal stimulus was measured following each microinjection. Compared to control, antinociception was significantly increased by hypocretin-1 and by SPA. SB-334867 increased nociceptive responsiveness, and administration of hypocretin-1 plus SB-334867 blocked the antinociception caused by hypocretin-1. These results suggest for the first time that hypocretin receptors in rat PnO modulate nociception. Perspective: Widely distributed and overlapping neural networks regulate states of sleep and pain. Specifying the brain regions and neurotransmitters through which pain and sleep interact is an essential step for developing adjunctive therapies that diminish pain without disrupting states of sleep and wakefulness.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalJournal of Pain
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Fingerprint

Adenosine A1 Receptor Agonists
Nociception
Sprague Dawley Rats
Sleep
Hot Temperature
Orexin Receptors
Pain
Microinjections
Purinergic P1 Receptor Agonists
Wakefulness
Hyperalgesia
Brain
Neurotransmitter Agents
Urea
Orexins
Pontine Tegmentum
1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Thermal Nociception is Decreased by Hypocretin-1 and an Adenosine A1 Receptor Agonist Microinjected into the Pontine Reticular Formation of Sprague Dawley Rat. / Watson, Sarah L.; Watson, Christopher J.; Baghdoyan, Helen; Lydic, Ralph.

In: Journal of Pain, Vol. 11, No. 6, 01.06.2010, p. 535-544.

Research output: Contribution to journalArticle

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