Lecture 8 - Debra Artim Lec Notes- Touch PDF

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Debra Artim Lec Notes- Touch...

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I.

II.

Pain, temp and Itch A. Pain is called nociception 1. Comes from nocere- to hurt 2. Literally means reception to hurting Pain A. Different than Somatosensory system 1. Somatosensory- different kinds of receptor with highly specialized ending for particular signal 2. Pain receptors= free nerve endings a) Have no specializations B. Separated into two broad categories

1. Nociception a) Happening at physiological level b) Happening at the skin going up to brain c) All of the encoding/processing of the pain signal itself d) Transferring of a pain stimulus into an electrical signal and sending that towards the brain 2. Pain

a) b) c) d) e)

Cognitive interpretation of ^that signal Unpleasant Produced negative emotional perception Requires processing at the level of the cortex Associated with real damage or potential damage, requires a higher level of brain processing to get higher level of interpretation 3. Analgesia a) Relief of pain

III.

Noxious Stimulus A. Any stimulus that is damaging to tissue or potentially damaging to tissue B. Can cause damage even if it does not necessarily cause damage in that moment C. When we have damage to our tissue it can hurt directly because of mechanoreceptor on pain neurons that are activated 1. Also when we damage our tissue it results in release of a lot of different chemical mediators a) These chemical mediators also act on pain neurons to send signals b) When we have tissue damage there are a lot of different ways that the tissue damage can result in pain 2. Damage to skin and muscle causes pain mechanically and through recruitment of immune cells and release of chemicals 3. Visceral damage-damage to your organs- will often cause pain but not necessarily D. Noxious stimuli are detected by pain neurons called Nociceptors

1. Free nerve ending branch and form a receptor field like somatosensory

neurons and are pseudounipolar (no dendrites, axon branches at the skin) a) Cell bodies reside in the dorsal root ganglia (1) In dorsal root ganglia have cell bodies of touch cells and pain/ temp which continue to project into the spinal cord b) First order/primary (1) Something has to infringe upon neuron, the first neuron that brings the info into your body (a) Goes from skin and into the spinal cord c) Second order/ secondary (1) The second neuron in the pathway (2) Neuron that has cell body in the spinal cord and has to take that info up the spinal cord towards the brain IV.

Nociceptors A. Have nerve endings that innervate our target B. Broken up into 2 groups 1. A delta fibers a) 2. C fibers C. The receptors are ion channels that are sensitive to mechanical, chemical and/or thermal stimulation 1. Ion channels are called TRP channels (transient receptor potential)

a) b) c) d) e)

Have graded potential coming through receptor Transient bc do not last for very long All TRP channels work the same way Permeable to Na+ and K+ Some express GPCR

V.

D. Two groups 1. Responsible for first pain and second pain a) First pain is the initial sharp intense pain right when you injure yourself (1) Transduced by A delta fibers (a) A delta fibers are myelinated (b) Fast pain b) Second pain dull ache that lasts a while- delayed after injury (1) Transduced by C fibers (a) C fiber is not myelinated (b) Slower throbbing pain Pain Categories- Nociceptive

A. Pain that is is mediated through pain receptors is called nociceptive pain 1. Pain that is transduced through A delta and C fibers through trp channels B. Nociceptive pain can come either from our somatosensory system or from

VI.

visceral organs 1. Visceral pain is less localized= more diffuse a) Because it has sparser innervation, not that many pain neurons so not as able to localize than somatosensory which is more densely innervated b) Visceral system is mostly mechanical pain receptors c) Gives rise to referred pain 2. Somatic pain a) More densely innervated Injury and Pain: Inflammation A. Tissue damage it can increase how sensitive we are to a painful stimulus close to the site of the injury 1. Called hyperalgesia

a) If you're already hurt it is easier to hurt that area again b) More sensitive to painful stimuli c) Due to inflammation

(1) Release of inflammatory mediators that sensitize our nociceptors making them easier to activate (2) aspirin/ acetylcholine are non steroidal inflammatory drugs (a) The reason they are effective is bc they are relieving inflammatory pain by blocking inflammatory response (3) Chemicals that are released due to tissue damage is called inflammatory soup- bc there is a lot of stuff that is put out into the extracellular fluid (a) Histamine, serotonin, ATP (b) All of these are released by proinflammatory molecules that lead to inflammatory pain (c) Each of these have receptors on nociceptive afferents

VII.

Pain Categories: Neuropathic Pain A. Pain that occurs when the pain neurons are injured and start to die

B. Can have damage to the receptors, spinal cord, brain areas that are involved in processing pain 1. Each will neuropathic pain C. Neuropathic pain is really hard to treat because it is non inflammatory so aspirins do not work 1. Due to death of neuron so there is nothing to do to restore that damage D. ex/ Shingles, pins and needles sensation, burning sensation, in the extremities, side effect of diabetes (diabetic neuropathic pain), stroke

VIII.

1. Treat using opiates but neuropathic pain is chronic E. Neuropathic pain has no purpose Sensory transduction

A. TRP channels can be activated by heat, chemicals, mechanical stimulation B. Permeable to Na+ and Ca+

IX.

1. When they open up Na+ comes in to depolarize if it is big enough to reach threshold neuron fires an action potential C. Spicy 1. Active ingredient in capsaicin which binds to TRPV1 which are activated by noxious heat 2. Why it feels hot- activates heat receptors in your mouth Pain Categories: Referred pain A. Dermatome

1. Spinal cord is organized with afferent neurons coming in and their cell bodies in the dorsal root ganglia which are synapsing on the 2nd order neurons in the spinal cord a) The dorsal root ganglion contains a lot of different somas from different pain neurons coming from different places 2. A dermatome is the area of skin that is innervated by all of the dorsal root ganglia neurons that enter in a single segment of the spinal cord a) ex/ Segment L5 look where neurons are coming from b) Receptive field for all of the neurons in the single dorsal root ganglia c) Its organization leads to referred pain B. Referred pain

X.

1. ex/ heart attack a) Symptoms: shooting pain down left arm b) Esophageal pain 2. Have primary neurons coming from the skin and coming from the heart, they are converging onto the same set of neurons in the spinal cord a) They are making multiple connections on the spinal cord but onto the same neurons b) Primaries come in synapse on the secondaries, secondaries send info to the brain (1) Carrying info that is not specific from the skin or viscera (2) So one single 2nd order neuron can be carrying pain from either one c) Brain misinterprets where info is coming from Endogenous Pain Relief

A. Nervous system has ways to produce relief of pain B. Endogenous analgesia 1. Have tissue that is bringing in the info/ tissue that is being damaged 2. Have A delta and C fibers taking this info to the spinal cord and onto the thalamus which projects onto primary somatosensory cortex so that we become aware of the pain 3. Which goes to the limbic system- emotional part- associate pain with negative emotion 4. ^^^ Ascending Pathway 5. From the cortex back down to the spinal cord, this area of the brain this is coming from is called the P.A.G (peri Aqueductal Grey) a) PAG is in the midbrain and the cortex is giving info to the PAG to say “ok i have received the pain info and we have done what we needed to do so we do not need that signal anymore so you can suppress it” b) The PAG projects down to the spinal cord and inhibits the pain signal coming down from the spinal cord (1) Body's own natural way of reducing pain signals once we do not need them anymore 6. ^^^^ Descending Pathway

C. Gate control theory of pain 1. Rubbing an area that you have hurt 2. Have C fiber comes in to the primary neuron which synapses onto the secondary neuron and sends a signal to the brain 3. There is an inhibitory interneuron within the spinal cord

a) Inhibiting second order neuron so that in the absence of any stimulus our 2nd order pain neurons are activated but when we are injured and have pain the C fiber inhibits the inhibitory interneuron b) The C fiber is doing two things: its is activating the the 2nd order pain neuron, it is turning off inhibition of that pain neuron (1) When we activate a C fiber we get a really strong pain signals in the brain c) However if the A delta fiber (which comes in the same neuron and direction as C fiber) coming from the mechanoreceptors on its way to the brain it sends off a little collateral that activates the inhibitory interneuron d) The C fiber is firing, if you also activate the mechanical receptor in the same area now this neuron is firing and action potential and can activate inhibitory neuron so the 2nd order neuron is sending a signal to the brain 4. Mechanical stimulation reduces the size of the pain signal that goes from the 2nd order neuron to the brain

D. The opposite can happen 1. Pain receptors can become sensitized so that they are even more sensitive to painful stimuli a) Giving a bigger stimulus 2. Called sensitization a) If you have really intense/long lasting pain b) Get increases in sensitivity of this pathway c) Easier to activate-lower threshold d) Lead to chronic pain which leads to nociceptors that are really easy to activate- pain from injury has subsided but can have chronic pain in the area 3. Have pain signal coming in and synapse be highly sensitive, have stimulus in the thalamus sensitized 4. Consequence of sensitization a) Hyperalgesia (1) Increase sensitivity to a stimulus that would have been painful anyways (a) Pinch occurs in a place that is already injured it is going to hurt more b) Aldenia (1) When something that is normally non painful becomes painful because of previous damage (2) When you are sunburnt, touching damaged sin c) Congenital insensitivity to pain (1) Rare disorder (2) Cannot feel pain (3) It occurs because they do not have a specific type of Na channel that exists in pain neurons

(a) Called Nav 1.7 (4) Function normally but none of their pain neurons can fire action potentials XI.

Pain treatment A. Clinically want to use the weakest pain relief drug that they can to get the patient sufficient pain relief

1. Start with mild and work way up B. Pharmacological Treatments 1. Prostaglandin and aleve a) All anti inflammatory b) Not blocking all the mediators just some c) Limit to how effective these drugs 2. Opioid a) Important for pain management b) For severe pain c) Work on on endogenous GPCRS called opioid receptors (1) Mu (2) Delta (3) Kappa d) Same receptors that mediate body's own natural pain relief e) Opium to oxycodone are working on these receptors f) Endogenous opioids

(1) Opioids our body naturally makes are endorphins, enkephalins g) Cannabis and morphine

(1) Relieve pain (2) Drugs work at the synapse between first order and second order neuron to reduce how much neurotransmission is happening at the synapse h) Mu, delta and kappa receptors are located both presynaptically and postsynaptically and all are GPCRs- metabotropic receptors (a) Activation in any of them leads to a decrease in neurotransmission through multiple mechanisms i) Mechanisms of opioid pain relief

XII.

(1) First order neuron coming into the spinal cord, second order neuron starting from the spinal cord and going up to the brain (2) Presynaptic receptors (a) Block Na+ current stopping neurotransmitter release (3) Postsynaptic neuron (a) Activation opens up a K+ channel and causes inhibitory PSP (4) Have presynaptic neuron release neurotransmitter on a cell that is already hyperpolarized (a) Combination of these two things reduces how much transmission that is happening at this synapse (b) Drastically reduces pain signal sent to brain (5) At the spinal cord, when the opiates activate the receptor they also decrease duration of action potential (a) Repolarizes faster (b) If AP is shorter it is going to let in less Ca+ and decrease release of neurotransmitters How signals are making it to the brain

A. Have receptors, have receiving centers in the spinal cord and the brain stem, have the integration center in the thalamus, and have perception in the cortex B. Mechanoreceptor afferents-red

1. Carrying touch, vibration, proprioception

C. Steps 1. Primary neurons enter the spinal cord and immediately starts traveling up

2. 3.

4.

5.

the spinal cord, Travels to the medulla in the brain stem where it synapses a) First order to second order synapse After it synapses it crosses over to the thalamus a) All sensory info crosses the midline the difference is where the crossing over happens b) Mechanosensory info comes in ascends and cross at the medulla Pain info comes (blue) into the spinal cord immediately synapses and crosses over a) Pain and temp info coming in is going to cross over at the same level of the spinal cord as it enters Both go to the thalamus and from the thalamus to the cortex

D. Dorsal Column-medial lemniscal pathway 1. Ascends in dorsal part of spinal cord 2. Medial lemsiculs- fibers that travel up to the thalamus E. Pain and Temp Pathway

1. Called anterolateral system a) Traveling in the anterior lateral part of the spinal cord 2. Key: enters, synapses immediately and crosses over and ascends

F. Results in different loss of function in different parts of the body depending on spinal injury 1. Touch vibration, does not cross over until reaches the brain stem

2. Pain and temp info crosses over as soon as it enters 3. If a person has damaged to the left side of the spinal cord a) What fibers are being damaged? b) Left side carries mechanical info (1) Lose pain and temp from opposite side...