Chronic stress, sensory hypersensitivity, anxiety-induced hyperalgesia .

Tori Collins

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

Rivat C et. al.

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

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

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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

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 CCK-dependent facilitatory pathways from the RVM A CCK-2 receptor antagonist may

provide pain relief in the context of anxiety-induced hyperalgesia

FIGHT THE POWER

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