[Abstract Title]. - Society for Neuroscience

MH45361
Title: Increase in antinociception caused by microinjection of hypocretin-1 (hcrt-1) into the
pontine reticular nucleus, oral part (PnO) of Sprague Dawley rat is blocked by the hcrt receptor-1
(hcrt-r1) antagonist SB-334867
Authors: *S. L. WATSON, A. S. BATTERSBY, C. J. WATSON, H. A. BAGHDOYAN, R.
LYDIC;
Dept Anesthesiol, Univ. Michigan, Ann Arbor, MI
Abstract: Sleep disruption is a common side effect of pain, but the mechanisms by which pain
inhibits sleep are not understood. Hcrt-1 is a hypothalamic peptide that enhances wakefulness
(reviewed in The Orexin/Hypocretin System: Physiology and Pathophysiology, edited by Nishino
and Sakurai, 2005), and microinjection of hcrt-1 into rat posterior hypothalamus (Pain 109:367,
2004) or PnO (J Pain 9 Suppl. 2:7, 2008) decreases responses to nociceptive input. This study is
testing the hypothesis that PnO microinjection of the hcrt-r1 antagonist SB-334867 blocks the
increase in antinociception caused by PnO microinjection of hcrt-1. Adult male rats (n=11) were
implanted with microinjection guide tubes. Paw withdrawal latency (PWL) was quantified using
an IITC Model 336T Paw Stimulator Analgesia Meter with a focused beam of light providing the
thermal, nociceptive stimulus. In separate experiments, the PnO was microinjected with 100 nL
of saline (control), hcrt-1 (35.6 ng; 0.1 mM), SB-334867 (0.34 ng; 0.01 mM), and hcrt-1 plus
SB-334867 (35.6 ng and 0.34 ng, respectively). Post-injection measurements of PWL (s) were
taken at 10, 20, 30, 60, 90, and 120 min. The PWL measurements were expressed as percent
maximum possible effect (%MPE) to account for individual animal differences and the thermal
stimulus cutoff time. Upon completion of testing, all microinjection sites were histologically
confirmed to be within the PnO. ANOVA for repeated measures indicated a significant drug
effect on %MPE (F=4.38; df=3, 33; p=0.0114). Tukey/Kramer post hoc comparisons test
revealed that hcrt-1 significantly (p