Tori Collins
CHRONIC STRESS, SENSORY
HYPERSENSITIVITY, ANXIETYINDUCED HYPERALGESIA.
Pain and Stress
 Chronic pain is an inescapable stress
 Many patients with chronic pain suffer from
depression
 Depressed patients have an altered
perception of pain
 Biggest risk factor for depression is chronic
stress
 Blackburn-Munros & Blackburn-Munro 2001
Pain integration
 Descending control of nociception plays a
role in how we experience acute and chronic
pain
 Nociceptive input is prioritized relative to
other homeostatic needs
 Descending control can be stimulatory or
inhibitory
 Can depend on behavioral, emotional and
pathological states
Pain integration
 Descending inhibition: intense stress and fear
are associated with hypoalgesia
 Descending facilitation: inflammation, nerve
injury, sickness, chronic opioid exposure are
associated with hyperalgesia
Pain integration
 The RVM can produce both analgesia and
hyperalgesia
 Opiods, OFF-cells: analgesia
 CCK, ON-cells: hyperalgesia
Chronic stress induces transient
spinal neuroinflammation,
triggering sensory
hypersensitivity and longlasting anxiety-induced
hyperalgesia
Rivat C et. al.
Intro
 After repetitive and sustained stress
adaptation is impaired
 Hypercortisolism
 Hypertension
 Neuropsychiatric disorders
 Immune system can be affected
 Increased inflammatory response
 Excess of COX-2 leads to neuronal damage
Intro
 Social defeat is a model for psychological
chronic stress
 Animals display anxiety/depression-like
behaviors
Methods
 Intruders (male Sprague-Dawley rats 300-
325g)
 Residents (male Long-Evans rats, 700-800g)
 Rats were divided into defeated intruders and
non-defeated intruders each receiving either
vehicle or drug
Social defeat
 Intruders were placed into resident’s cage for
45 min periods on 4 consecutive days
 Period 1: no physical contact
 Period 2: either intruder was defeated by resident
or resident was removed and intruder allowed to
explore freely (non-defeated group)
Experimental design
Elevated plus maze
Methods
 Nociceptive sensitivity was assessed with von
Frey and Randall-Selitto tests
Methods
 Formalin was injected under the skin on the
dorsal surface of the hindpaw and pain
responses were recorded for 70 min
 Pain is assessed on a 5 level scale according
to posture
 Ex. 0 = normal posture, 4 = shaking, licking or
biting of paw
Figure 1
Figure 2
Figure 3
Figure 3
Figure 4
Figure 5
Figure 5
Figure 6
Figure 7 7
Figure 7 7
Discussion
 Psychological stress produced a transient
plastic change in the spinal cord
 Spinal inflammation was correlated with
mechanical sensory hypersensitivity
 RVM-CCK dependent descending pathways
 Distinct mechanisms for sensory hypersensitivity
and formalin-induced hyperalgesia
Discussion
 Spinal neuroinflammation was related to
sensory hypersensitivity mediated by iNOS
and COX-2 but not to anxiety
 The inflammation was linked to the stress
itself, not the anxiety state produced by the
stress
Discussion
 The decrease in pain threshold in the rats
exposed to social defeat was related to CCKdependent facilitatory pathways from the
RVM
 A CCK-2 receptor antagonist may provide pain
relief in the context of anxiety-induced
hyperalgesia
FIGHT THE POWER
 http://www.youtube.com/watch?v=WmBrEQ
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