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New Translational Research Reveals a Useful Model for Studying Chronic Stress-Induced Hypersensitivity to Pain

Results from a new study offers insight into the brain’s circuitry involved in stress-induced hyperalgesia (SIH),


which may help lead to a better understanding of the development and maintenance of chronic pain states in patients suffering with conditions such as post traumatic stress disorder (PTSD), fibromyalgia and neuropathic pain. This study was presented today at the American Academy of Pain Medicine’s 27th Annual Meeting.

Edward Bilsky, PhD, a Professor in the College of Osteopathic Medicine and Director of the Center for Excellence in the Neurosciences at the University of New England (UNE), presented results from a study today that examined the role of the rostral ventromedial medulla in a rat model* of stress-induced hypersensitivy to pain. The study was co-authored by fellow UNE colleagues, Ian D. Meng, PhD, and second year medical student Jacques Reynolds.

The rostral ventromedial medulla (RVM) is a brainstem structure that sends signals down to the spinal cord region and modulates sensory information coming into the central nervous system from the body. Dr. Meng referred to the RVM as “an amplifier, regulating the volume of the pain signals coming into the brain.” It has been well documented that the pain inhibitory systems descending from the brainstem to the spinal cord and medullary dorsal horn underlie stress-induced analgesia (SIA), the phenomenon of pain suppression upon exposure to unconditioned or conditioned stressful stimuli.

This study examined the opposite of SIA, stress-induced hyperalgesia (SIH), which activates a very selective kind of neuron in the RVM region that is involved in turning the pain signal up. The role of the RVM in SIH remains relatively unknown, however, it is known that in chronic pain conditions these neurons in the RVM become active and increase the pain signals coming from the spinal column. The researchers set out to examine the effect of chronic low-level stress and how it may actually increase one’s pain signals to the brain.

The researchers used a rat model to investigate the involvement of the rostral ventromedial medulla (RVM) in tactile hypersensitivity induced by repeated bouts of experimentally provoked defensive, aggressive, and hypervigilant behavior. A subset of animals received RVM microinjections of the toxin conjugate, dermorphin-saporin or its control, saporin, 14 days prior to each behavioral run. Repeated stimulation of the whisker pad resulted in an agitated rat including a very aggressive response to additional presentation of the stimuli.

Stressed animals showed increased mechanical sensitivity as compared to controls. However, the onset of hypersensitivity was prevented by RVM microinjections of dermorphin-saporin, but not saporin. Taken together, these results suggest a novel model for the study of stress-induced hypersensitivity. Additionally, descending facilitation from the RVM plays a critical role in producing SIH.

One of the things observed in rats was a hypervigilant state, where after a number of exposures to these filaments the rats were on guard and ready. “This may model aspects of what soldiers experience in the battlefield in places like Afghanistan and Iraq where soldiers are on guard 24-7, never knowing when the enemy will attack. This type of stress is unremitting and more of a man-made type of stress event. Physiologically, our systems are not well prepared to handle that kind of a stressor, and that may be contributing to some of these chronic pain states, especially in conditions such as PTSD,” Dr. Bilsky states.

The researchers hope to define what types of stressors lead to greater amounts of pain and understand the circuitry involved in SIH. “There appears to be relationships between the circuitry that we are studying in the rats and certain types of stressors and clinical conditions. Understanding this relationship could lead to the development of better treatments and have positive clinical implications,” Dr. Bilsky concludes.

*All protocols were approved by the Institutional Animal Care and Use Committee (IACUC) at the University of New England and adhered to the guidelines of the “Principles of laboratory animal care.”

For more information: www.painmed.org/press

News source: The American Academy of Pain Medicine

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