Somatosensory System and Pain

1. 08-9 פיסיולוגיה מורחב Somatosensory System and Pain lecture 7: Descending control Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for research on Pain Institute of Life Sciences Hebrew University of Jerusalem

2. descending pathways

3. Beecher HK (1946) Pain in Men Wounded in Battle. Ann Surg. 123:96–105: “Three-quarters of badly wounded men, although they have received no morphine for hours... have so little pain that they do not want pain relief medication” 7th century, Battle of Handak shi,suni

4. Miczek et al. Analgesia אלחוש Stress-induced analgesia

5. Response latency (sec) 0 10 20 0 Time after injection 80 min Morphine analgesia hotplate test morphine morphine + naloxone vehicle naloxone.. μ receptor antagonist

6. Miczek et al. Analgesia אלחוש endogenous opioids (enkephalins neurotransmitter,  endorphin circulation) Stress-induced analgesia vehicle naloxone multiple pinch control

7. Endogenous Opioids enkephalins (neurotransmitter)  endorphin (circulation) POMC

8. PAG (midbrain periaqueductal grey) e- stim  analgesia (hp) [naloxone reversible] Liebeskind et al. 1970s

9. hp response latency pre post PAG stim/ μinject

10. PAG (midbrain periaqueductal grey) e- stim  analgesia (hp) [naloxone reversible] …. later morphine microinjection Liebeskind et al. 1970s

11. PAG  analgesia WDR neuron during PAG stimulation

12. anterograde tracer PAG RVM RVM retrograde tracer arm cut DLF leg Systemic morphine (and endogenous opiates) acts primarily in the brainstem to activate a descending control circuit PAG periaqueductal grey RVM rostro-ventromedial medulla NRM nucleus raphe’ magnus DLF dorsolateral funciculus

13. there is evidence that placebo analgesia may be due to endogenous opioids

14. 0 100 worst pain possible no pain VAS (Visual Analog Scale) אך למדוד את הכאב באדם ?

15. מידת הכאב זמן • regression to the mean • belief, expectation,conditioning אמונה טפלה placebo analgesia אינבו

16. internal mammary artery ligation surgery for angina pain (1940s,50s)  pain relief often >6 months "sham surgery"  identical result Arthroscopic surgery for osteoarthritis of the kneeMoseley et NEJM 2002 "placebo effect"

17. "אפקטשל הפלצבו" placebo effect ללא טיפול מידת הכאב Advil, Neurofen טיפול פלצבו טיפול תרופתי או כירורגי אפקט התרופה נטו net drug effect סה"כ אפקט התרופה overall drug effect זמן Drug efficacy

18. Pain perception under hypnotic suggestion (fixed stimulus) Rainville et al. 1997

19. intracutaneous capsaicin then report pain intensity Benedetti et al.

20. placebo analgesic cream • placebo effect eliminated • by (hidden) systemic naloxone intracutaneous capsaicin then report pain intensity

21. acupuncture ? homeopathy ? magnets ? crystals ? prayer ? physiotherapy ? RCTs randomized placebo-controlled trials

22. placebo the placebo effect VAS cummulative buprenorphine dose post-thoracotomy pain PCA buprenorphine told: nothing, either, analgesic

23. "בצד החיובי, סידרת לי את כאבי הגב"

24. primary sensory neurons

25. פיסיולוגיה מורחב Somatosensory System and Pain lecture 7: Descending control Prof. Marshall Devor, Ph.D. Dept. of Cell & Animal Biology and Center for research on Pain Institute of Life Sciences Hebrew University of Jerusalem