SRI International Research Sheds Light on Fight-or-Flight Response

MENLO PARK, CA–(EMWNews – July 16, 2008) – SRI International researchers have found

that the direct interaction between two neuropeptide systems —

hypocretins/orexins (Hcrt) and nociceptin/orphanin FQ (N/OFQ) — is

responsible for stress-induced blockage of pain. Stress-induced analgesia

(SIA) is a key component of the body’s defensive behavioral

“fight-or-flight” response. When individuals find themselves in

life-threatening or other highly stressful situations, they are often able

to ignore physical pain to accomplish tasks that might not otherwise seem

possible. While the roles of certain neural substrates have been studied in

the regulation of SIA, the neural pathways have been poorly understood

until now. These new findings provide a better understanding of the

critical role of these neuropeptides in SIA.

This ongoing research is a collaboration between two groups at SRI whose

leaders were originally involved in the discovery of these neuropeptides:

Thomas Kilduff, Ph.D. (co-discoverer of Hcrt in 1998 while at the Scripps

Research Institute, La Jolla, Calif.) and Lawrence Toll, Ph.D.

(co-discoverer of N/OFQ in 1995 while at the Centre National de la

Recherche Scientifique, Toulouse, France). The SRI research team, which

includes Drs. Xinmin Xie, Toll, and Kilduff, proposes that Hcrt neurons can

have a potent neuromodulatory effect on a variety of physiological systems

in the central nervous system (CNS). The team’s findings were recently

published in the Journal of Clinical Investigation (JCI) 2008 July 1;

118(7): 2471-2481, available online at www.jci.org.

“Stress-induced analgesia is critical to performance in a fight-or-flight

situation, but if prolonged it can be detrimental to physical and mental

health,” said Dr. Kilduff, SRI senior director of neurobiology and a

consulting professor at the Stanford University School of Medicine. “This

research helps us better understand the process of regulating SIA by

demonstrating the critical roles of Hcrt and N/OFQ.”

“N/OFQ may influence a variety of Hcrt-mediated actions beyond SIA,

including sleep, wakefulness, stress and addiction,” said Lawrence Toll,

SRI senior director of neuropharmacology. “This research opens doors to

study the interaction between these systems in other stress-related medical

conditions such as anxiety, drug abuse and post-traumatic stress disorder.”

The team’s paper in JCI is titled “Hypocretin/orexin and

nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of

stress-induced analgesia.” The research was conducted by Xinmin Xie (SRI

International and AfaSci, Inc.), Jonathan P. Wisor (SRI International),

Junko Hara (SRI International), Tara L. Crowder (SRI International), Robin

LeWinter (SRI International), Taline V. Khroyan (SRI International),

Akihiro Yamanaka (University of Tsukuba, Japan), Sabrina Diano (Yale

University School of Medicine), Tamas L. Horvath (Yale University School of

Medicine), Takeshi Sakurai (University of Tsukuba), Lawrence Toll (SRI

International) and Thomas S. Kilduff (SRI International and Stanford

University School of Medicine).

About SRI International

Silicon Valley-based SRI International (www.sri.com) is one of the world’s

leading independent research and technology development organizations.

Founded as Stanford Research Institute in 1946, SRI has been meeting the

strategic needs of clients and partners for more than 60 years. The

nonprofit research institute performs sponsored research and development

for government agencies, businesses, and foundations. In addition to

conducting contract R&D, SRI licenses its technologies, forms strategic

partnerships, and creates spin-off companies.