Chronic stress, sensory hypersensitivity, anxiety-induced hyperalgesia .

1. Tori Collins Chronic stress, sensory hypersensitivity, anxiety-induced hyperalgesia.

2. 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

3. 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

5. 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

6. Pain integration • The RVM can produce both analgesia and hyperalgesia • Opiods, OFF-cells: analgesia • CCK, ON-cells: hyperalgesia

7. Chronic stress induces transient spinal neuroinflammation, triggering sensory hypersensitivity and long-lasting anxiety-induced hyperalgesia Rivat C et. al.

8. 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

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

10. 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

11. 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)

12. Experimental design

13. Elevated plus maze

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

15. 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

16. Figure 1

17. Figure 2

18. Figure 3

19. Figure 3

21. Figure 4

22. Figure 5

23. Figure 5

24. Figure 6

25. Figure 7 7

26. Figure 7 7

27. 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

28. 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

29. 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

30. FIGHT THE POWER • http://www.youtube.com/watch?v=WmBrEQ6Kh9o