Article

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

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan 48109-5615, USA.
The journal of pain: official journal of the American Pain Society (Impact Factor: 4.22). 12/2009; 11(6):535-44. DOI: 10.1016/j.jpain.2009.09.010
Source: PubMed

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 A(1) receptor agonist N(6)-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.

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Available from: Christopher J Watson, Apr 02, 2014
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    • "There are several evidence indicating the involvement of orexin-A in modulation of nociceptive behavior (Yamamoto et al., 2003; Holland et al., 2005; Y.K. et al., 2005). For example, it has been reported that orexin-A microinjection could induce analgesia in different parts of the brain via affecting OX1R (Watson et al., 2010; Azhdari Zarmehri et al., 2011). Also, studies have demonstrated that OX1R is involved in the development of morphine induced analgesia and tolerance (Ranjbar-Slamloo et al., 2012; Erami et al., 2012; Azhdari-Zarmehri et al., 2013). "
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    • "In all of those models, the orexin-induced analgesic effects were suppressed by the OX1 receptor antagonist SB-334867 but not by naloxone, an opioid receptor inverse agonist, suggesting that regulation of nociception by orexin is independent of the opiate system (Figure 2). In addition to the direct projection of orexin neurons to the spinal cord (van den Pol, 1999), orexin signalling in the posterior hypothalamic area (Bartsch et al., 2004), the pontine reticular nucleus, oral part (Watson et al., 2010), and periaqueductal gray matter have been shown to be important for its antinociceptive effects. Moreover, orexin plays a significant role in the regulation of stress-induced analgesia (SIA), coordinating with the nociceptin/orphanin FQ systems (Xie et al., 2008; Gerashchenko et al., 2011). "
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