Tori Collins - USD Biology
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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
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