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פיסיולוגיה מורחב 08-9 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 descending pathways 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 Miczek et al. Stress-induced analgesia Morphine analgesia Response latency (sec) 20 10 0 hotplate test morphine morphine + naloxone vehicle 0 Time after injection 80 min naloxone.. μ receptor antagonist Miczek et al. Stress-induced analgesia vehicle naloxone endogenous opioids multiple pinch control (enkephalins neurotransmitter, endorphin circulation) Endogenous Opioids enkephalins (neurotransmitter) endorphin (circulation) POMC PAG (midbrain periaqueductal grey) e- stim analgesia (hp) [naloxone reversible] Liebeskind et al. 1970s hp response latency pre post PAG stim/ μinject PAG (midbrain periaqueductal grey) e- stim analgesia (hp) [naloxone reversible] …. later morphine microinjection Liebeskind et al. 1970s PAG analgesia WDR neuron during PAG stimulation Systemic morphine (and endogenous opiates) acts primarily in the brainstem to activate a descending control circuit anterograde tracer PAG RVM RVM retrograde tracer arm cut DLF PAG periaqueductal grey RVM rostro-ventromedial medulla NRM nucleus raphe’ magnus DLF dorsolateral funciculus leg there is evidence that placebo analgesia may be due to endogenous opioids ? אך למדוד את הכאב באדם no 0 pain 100 worst pain possible VAS (Visual Analog Scale) • regression to the mean • belief, expectation,conditioning אמונה טפלה placebo analgesia אינבו זמן 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 knee Moseley et NEJM 2002 "placebo effect" Drug efficacy "אפקט של הפלצבו" placebo effect ללא טיפול Advil, Neurofen טיפול פלצבו אפקט התרופה נטו net drug effect סה"כ אפקט התרופה overall drug effect טיפול תרופתי או כירורגי זמן Pain perception under hypnotic suggestion (fixed stimulus) Rainville et al. 1997 intracutaneous capsaicin then report pain intensity Benedetti et al. intracutaneous capsaicin • placebo analgesic cream then report pain intensity • placebo effect eliminated by (hidden) systemic naloxone acupuncture ? homeopathy ? magnets ? crystals ? prayer ? physiotherapy ? RCTs randomized placebo-controlled trials placebo the placebo effect post-thoracotomy pain PCA buprenorphine told: nothing, either, analgesic "בצד החיובי ,סידרת לי את כאבי הגב" primary sensory neurons 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
