Chronic stress, sensory hypersensitivity, anxiety-induced hyperalgesia.

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Chronic stress, sensory hypersensitivity,
anxiety-induced hyperalgesia.

• Tori Collins

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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

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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

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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

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Pain integration

• The RVM can produce both analgesia and
  hyperalgesia
• Opiods, OFF-cells analgesia
• CCK, ON-cells hyperalgesia

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Chronic stress induces transient spinal
neuroinflammation, triggering sensory
hypersensitivity and long-lasting anxiety-induced
hyperalgesia

• Rivat C et. al.

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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

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Intro

• Social defeat is a model for psychological
  chronic stress
• Animals display anxiety/depression-like behaviors

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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

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Social defeat

• Intruders were placed into residents 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)

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Experimental design
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Elevated plus maze
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Methods

• Nociceptive sensitivity was assessed with von
  Frey and Randall-Selitto tests

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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

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Figure 1
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Figure 3
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Figure 4
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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

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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

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Discussion

• The decrease in pain threshold in the rats
  exposed to social defeat was related to
  CCK-dependent 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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FIGHT THE POWER

• http//www.youtube.com/watch?vWmBrEQ6Kh9o