Term
| What are the 4 categories of pain? |
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Definition
- Physiologic pain - 'ouch' pain, an early warning sign. Also called nociceptive
- Inflammatory pain - due to lowered pain threshold from prostaglandins. Hyperalgesia/allodynia - painful stimuli that doesn't normally cause pain.
- Neuropathic pain - pathological, persistant pain due to nerve damage
- Dysfunctional pain - abnormal nerve function such as fibromyalgia |
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Term
| What is the difference between physiologic, acute, and chronic pain? |
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Definition
- Physiologic - Absence of tissue damage --> protective
- Acute - injury occurs, activation of nociceptive receptors. Healing occurs
- Chronic - Triggered by injury or disease, perpetuated by other factors. |
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Term
| What is the difference between nociceptive pain and neuropathic pain? |
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Definition
- Nociceptive - tissue damage occurs. Can be superficial, deep, or visceral.
- Neuropathic - Damage to or dysfunction of nerves - peripheral or central, fault signals |
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Term
| What are 3 potential targets for drug therapy? |
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Definition
- Interfere with the response of primary sensory neurons
- Interfere with the relay of algesic information
- Interfere with the perception of a painful response. |
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Term
| What are the 4 processes in pain signalling? |
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Definition
- Transductions/Nociception - primary afferent nerve fiber from periphery to spinal cord
- Transmission - First order neuron synapses w/ second order
- Perception - to the thalamus. 2nd order synapses w/ 3rd order
- Modulation - reception from 3rd order = PAIN |
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Term
| How does transduction take place in pain signalling? |
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Definition
| The first step, transduction, starts with a first order neuron. Neuron has receptors for thermal, mechanical, or chemical stimuli. An influx of Ca/Na --> depolarization and propagation of signal |
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Term
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Definition
- Sensory organs that respond to damaging stimuli. Usually TYPE C (unmyelinated) and a type of type A fiber which is thinly myelinated.
Are polymodal (Can receive different stimuli)
- receptors must be depolarized by GPCRs or Ion channels (faster) |
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Term
| What are different receptors for different stimuli? |
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Definition
- Thermal - TRPV for heat, TRPA/PM for cold
- Mechanical - TRPA, a pin prick or pinch
- Chemical - GPCRs or TRPAs, usually inflammation receptors |
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Term
| What is peripheral sensitization? |
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Definition
Increased responsiveness by lowering threshold for activation --> hyperalgesia or allodynia.
- Hyperalgesia - increased response by increased mediators/inflammation
- Allodynia - Pain to a stimuli that normally does not provoke pain
- Increased pain vs. pain where there is usually not pain. |
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Term
| How does Hyperalgesia occur? |
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Definition
- Enhanced influx of sodium or potassium. A stimuli results in increased NA/Ca influx and membrane depolarization through TRP channel
- Reduction in activation threshold - Adenylyl cyclase --> PKA phosphorylates NA channel --> decr in activation threshold, increase in ion influx
- Neurogenic inflammation increases mediator release --> BK or prostaglandins increase Na/Ca influx through TRP |
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Term
| What is orthodromic and antidromic? |
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Definition
Orthodromic - Conduction of an impulse towards the spinal cord
Antidromic -opposite direction, drives release of Substance P --> releases other mediators. |
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Term
| How does Transmission occur? |
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Definition
Depolarization of specific sodium channels on a first order neuron. Sensitizing agents (BK, prostaglandins) allow a decr in activation threshold.
- Type Adelta fibers are myelinated, use glutamate
- Type C fibers are unmyelinated, use substance P (slow)
- Transmission from a type A or C fiber to the dorsal horn, laminae 1, 2, and 5 receive impulse. HERE synapses with 2nd order neuron
- 2 tracts: neospinothalamic tract (fast sharp pain) and paleospinothalamic tract (slow response) |
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Term
| What is the difference between a fast response and a slow response in the dorsal horn? |
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Definition
-Fast - Type A fibers use glutamate. Ionotroptic AMPA/NMDA receptors
-Slow - Type C fibers use Substance P. Calcium N-channel (where prialt and Neurontin work) releases Sub P --> binds to NK1, a GPCR
- Anything that interferes with calcium transmission is analgesic - direct or indirect blockage. |
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Term
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Definition
PAG allows perception of pain, where a 2nd order neuron can synapse - destination of paleospinothalamic tract (slow pain)
3rd order neurons leave this site. |
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Term
| How does perception of pain work? |
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Definition
Thalamus relays sensory impulses to cerebral cortex.
- Hypothalamus sends efferents to PAG and LC
- LC - Projects efferents to dorsal horn to release NE
- Raphe magnus - inhibits pain by serotonin release |
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Term
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Definition
Via descending pathways back to dorsal horn using NE from locus coerulus and serotonin from raphe magnus
4 sites in the brain: hypothalamus, PAG, RM, LC
1 in the periphery: Dorsal horn |
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Term
| What neurotransmitters work to inhibit pain? |
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Definition
- GABA - increases chlorine to hyperpolerize a neuron - INHIBITORY
- Glycine - no drug action here
- Serotonin - releases from raphe nuclei to be inhibitory. post-synaptically inhibits depolarization
- NE - releases from locus coeruleus to be inhibitory. Alpha 2 receptor stimulation inhibits N-channel calcium influx - nerve can't depolarize. Post-synaptically, K efflux |
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Term
| How does Enkaphalin work? |
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Definition
An endogenous opioid
Release (via serotonin) inhibits glutamate and Sub P |
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Term
Do opioids work in neuropathic pain?
What is neuropathic pain? |
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Definition
No! No damaged tissue
Nerve damage causes inflammation and an UPREGULATION of sodium channels - increased nerve excitability
- enhanced influx, reduced threshold, inflammation, ectopic pacemakers, upregulation of NMDA receptors (ketamine), decreased endogenous analgesia |
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Term
| What cranial nerve can be involved in neuropathic pain? |
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Definition
| Trigeminal nerve (5) due to vascular compression |
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