lect fin fall 2020

pain.md

@@ -3,11 +3,15 @@
 * Submodality of the sense of touch, warns of injury and things that should be avoided
 * More subjective than the other senses. The same stimulus can produce different responses in different individuals, or in the same individual in different circumstances
 
+
 <!-- <div style="width:430px; float:left;"><iframe src="https://www.youtube.com/embed/s28fCIQKJTA" width="420" height="315"></iframe><figcaption>Congenital insensitivity to pain</figcaption></div> -->
 
 
 Note:
 
+nociceptive  
+: of or related to pain arising from stimulation of nerve fibers  
+
 Congenital insensitivity to pain
 
 [from: http://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain](http://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain)
@@ -53,8 +57,8 @@ Note:
 
 ## Heat gated ion channels
 
-* Capsaicin receptors are nonselective cation channels opened by heat, low pH, and capsaicin (the hot in hot peppers)
-* Mice without TRPV1 (VR1) have impaired sensitivity to pain. Can drink capsaicin as if it were water
+* Capsaicin receptors are nonselective cation channels opened by heat, low pH, and capsaicin (the hot in hot peppers)[^Caterina1997]
+* Mice without TRPV1 (VR1) have impaired sensitivity to pain. Can drink capsaicin as if it were water[^Caterina2000]
 
 <div><img src="figs/Neuroscience5e-Box-10A-1R_76f8dec.jpg" height="200px"><figcaption>Neuroscience 5e Box10A</figcaption></div>
 <div><img src="figs/Neuroscience5e-Box-10A-4R_b4cd22c.jpg" height="300px"><figcaption>Neuroscience 5e Box10A</figcaption></div>
@@ -62,6 +66,10 @@ Note:
 
 Note:
 
+[^Caterina1997]: Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997 Oct 23;389(6653):816-24. doi: 10.1038/39807. PMID: 9349813.
+
+[^Caterina2000]: Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000 Apr 14;288(5464):306-13. doi: 10.1126/science.288.5464.306. PMID: 10764638.
+
 transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor or the vanilloid receptor 1 (VR1)
 
 function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception).
@@ -128,7 +136,7 @@ Note:
 ## Hyperalgesia
 
 * Enhanced sensitivity and response to stimulation of the area around the damaged tissue. Stimuli that would not ordinarily be perceived as pain now is. For example after a sunburn a normal shower now feels painful
-* Due to the release of stuff from the damaged cells, such as prostaglandins, bradykinin, histamine, serotonin, ATP, can increase the sensitivity of nociceptors by interacting with the channel (directly or indirectly) and making it open easier, or by interacting with other receptors on nociceptive fibers to potentiate activity of TRP channels
+* Due to the release of substances from the damaged cells (e.g. prostaglandins, bradykinin, histamine, serotonin, ATP) that increase sensitivity by interacting with the nociceptor ion channels (directly or indirectly). and making it open easier, or by interacting with other receptors on nociceptive fibers to potentiate activity of TRP channels
 * Aspirin and ibuprofen inhibit cyclooxygenases (COX-2 inhibitors), necessary for prostaglandin synthesis
 * Shows that pain and injury are inter-related
 
@@ -148,7 +156,7 @@ central sensitization (pain memories)-- is a CNS disease, not a symptom of other
 
 Sensory discriminative (SI and SII) and affective motivational (limbic system activated, including cortical areas anterior cingulate gyrus, insular cortex (between parietal and temporal lobes ventral to S1)) dimensions of the pain experience. (MC Bushnell, Basbaum lecture).   **Anterior cingulate gyrus positively correlates with unpleasant experience**
 
-More fMRI brain activation (amplitude and size of actiation) in parts of brain with same painful stimulus for females vs males. Pain threshold almost the same (45degs hot) between the sexes but is a little bit lower for women. But pain tolerance is much higher in women. (Casey et al, Basbaum lecture). Who can tolerate delivering a baby.
+More fMRI brain activation (amplitude and size of activation) in parts of brain with same painful stimulus for females vs males. Pain threshold almost the same (45degs hot) between the sexes but is a little bit lower for women. But pain tolerance is much higher in women. (Casey et al, Basbaum lecture). Who can tolerate delivering a baby.
 
 Expectancy can alter pain (sawamoto 2000 interesting fMRI study, after Basbaum lecture 51:07). Imaging the brain of an empathetic spouse (female) reveals activity patterns characteristic of a spouse that is in pain (no citation someone from germany, Basbaum lecture 52:27)
 
@@ -167,10 +175,10 @@ Most interact directly with the receptors or ion channels of the nociceptive fib
 
 **Prostaglandins reduce the threshold depolarization needed for AP generation by phosphorylation of special TTX resistant Na+ channels expressed in nociceptor afferents and also incr levels of cAMP.**
 
-Cells that contribute to this inflammatory soup include mast cells, patelets, basophils, macrophages, neutrophils, endothelial cells, keratinocytes, and fibroblasts. Cells are responsible for releasing protons (lowering the pH), arachidonic acid, bradykinini, histamine, serotonini, prostaglandins, neucleotides, NGF, cytkines (interleukin 1beta, and TNF-alpha).  COX2 inhibitors, NSAIDs -- or nonsteroidal anti-inflammatory drugs block Cox-1 and Cox-2 enzymes so that prostaglandins can't be made.
+Cells that contribute to this inflammatory soup include mast cells, patelets, basophils, macrophages, neutrophils, endothelial cells, keratinocytes, and fibroblasts. Cells are responsible for releasing protons (lowering the pH), arachidonic acid, bradykinini, histamine, serotonin, prostaglandins, neucleotides, NGF, cytokines (interleukin 1beta, and TNF-alpha).  COX2 inhibitors, NSAIDs -- or nonsteroidal anti-inflammatory drugs block Cox-1 and Cox-2 enzymes so that prostaglandins can't be made.
 
 
->a peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to fall
+<!-- >a peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to fall -->
 
 nociceptive  
 : of or related to pain arising from stimulation of nerve fibers  
@@ -181,8 +189,9 @@ nociceptive
 
 * Spinothalamic tract
 * Cell bodies found in the most lateral parts of the dorsal root ganglia, but not discretely localized.
-* Innervate neurons in the dorsal horn of the spinal cord.  Some of these neurons project within the spinal cord.  These are important for reflex behaviors.
-* Others project axons cross the midline in the same segment and then go up to the brain.
+* Innervate neurons in the dorsal horn of the spinal cord.
+    - Some of these neurons project within the spinal cord.  These are important for reflex behaviors.
+    - Others project axons that cross the midline in the same segment and then go up to the brain.
 
 Note:
 
@@ -313,13 +322,14 @@ Innervation of same neuron in the dorsal horn of the spinal cord.
 
 ## Pain perception is subjective
 
-* Rubbing the site of injury can make pain less severe. Soldiers wounded in battle feel less pain than if one gets the same injury at home
 * Pain can be subjective. Depends on context.
-* There is a descending pain pathway that can impinge on the dorsal horn to quiet neurons
+    - Rubbing the site of injury can make pain less severe. 
+    - Soldiers wounded in battle feel less pain than if one gets the same injury at home
+* Why? There is a descending pain pathway that can impinge on the dorsal horn to quiet neurons
 
 Note:
 
-e.g. prostaglandins lower threshold for  phosphorylation of TTX resistant sodium channels. 
+e.g. prostaglandins lower threshold by phosphorylation of TTX resistant sodium channels. 
 
 TrPV1 receptor potentiations. 
 
@@ -424,15 +434,27 @@ endogenous opioids
 Note:
 
 - mind separate from body. No– this highlights something that neuroscientists already widely accept, that you cannot separate the mind from the body, the mind is body and vice versa
-- what is or is not reality philosophers
+- what is or is not reality-- philosophers
 - highlights descending control and higher order processing of pain
 - endogenous opioids
 
-- children are not placebo reactors less than 10 yr old. acupuncture works likely as a placebo (needle can be stuck anywhere). Hypnosis can alter perception (reduce activity in anterior cingulate) without sensory discrimination (Rainville Science 1997). But not sensitive to naloxone, so not through opiate system.
+- children are not placebo reactors less than 10 yr old. 
+- acupuncture works likely as a placebo (needle can be stuck anywhere). 
 
-- hypnosis (80% of people can be hypnotized)
-- 35% of people are placebo reactors
+Placebo (wn -over)  
+: an innocuous or inert medication; given as a pacifier or to the control group in experiments on the efficacy of a drug
 
+Placebo  
+: not well defined, especially trying to test therapeutic effects of non-pharmacological treatments (acupuncture)   
+: part of *every* treatment. Human touch, interaction, care compared with isolation and pain  
+
+Musial Front Neurosci 2019: https://doi.org/10.3389/fnins.2019.01110
+Vincent and Lewith J R Soc Med. 1995: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1295163/
+
+<!-- - Hypnosis can alter perception (reduce activity in anterior cingulate) without sensory discrimination (Rainville Science 1997). But not sensitive to naloxone, so not through opiate system. -->
+
+<!-- - hypnosis (80% of people can be hypnotized) -->
+<!-- - 35% of people are placebo reactors -->
 
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 ## Phantom limbs and phantom pain