Pain Plasticity

what are nociceptors

receptors that terminate free nerve endings and respond to noxious stimulus and generate nerve impulses that the brain perceive as pain signals

what do nociceptors respond to

noxious stimulus

what do nociceptors generate

nerve impulses that the brain perceive as pain signals

what stimuli do nociceptors respond to

thermal-mechanical and chemical

what are the 4 neural steps in the processing of pain signals

transduction, transmission, modulation, and perception

transduction

noxious stimuli are converted to electrical signals in sensory nerve endings

transmission

neural events which relay the information from the periphery to the cortex

modulation

the nervous system can selectively inhibit the transmission of pain signals

perception

subjective interpretation by the cortex of the noxious stimulus

what are the 2 components of perception

sensory component and affective component

what is the therapeutic goal for pain

eliminate abnormal pain without interfering with normal - protective pain

nociceptive pain processing

Noxious stimuli (Heat, cold, intense mechanical force, chemical irritants) -> nociceptor -> spinal cord -> adaptive, high-threshold pain early warning system (protective)

what is the response to nociceptive pain

autonomic response withdrawal reflex

inflammatory pain processing

peripheral inflammation & tissue damage -> spinal cord -> adaptive, low-threshold pain; tenderness promotes reapari (protection)

what are the 4 potential

macrophage, mast cell, neutrophil, and Granulocyte

name the 2 paths for pathological pain processing

neuropathic pain and dysfunctional pain

neuropathic pain pathway

neural lesion, positive and negative symptoms -> peripheral nerve damage -> abnormal central spinal processing -> stroke
OR
-> maladaptive , low-threshold pain disease state of nervous system

dysfunctional pain pathway

no neural lesion, no inflammation, positive symptoms -> normal peripheral tissue and nerves -> abnormal central spinal processing -> maladaptive, low-threshold pain disease state of nervous system

what kind types of pain and their central processing goes with spontaneous pain & pain hypersensitivity

inflammatory and pathological pain

what is familial erythromelalgia

autosomal-dominant condition with painful spontaneous burning pain of feet and/or hands, increased skin temp

what mutation causes Erythema

mutations in SCN9A - encoding a sodium channel alpha subunit

characteristics of Aß-fibers

Myelinated Non-nociceptive; Vary Fast conduction; convey light touch and vibration; may become nociceptive after nerve injury

what do Aß-fibers convey

light touch and vibration

what can afferent nerve fiber can become nociceptive after injury

Aß-fibers

characteristics of Aδ-fibers

Myelinated Nociceptors; fast conduction; convey fast "picking" pain, punctate stimuli, cold, thermal

what do Aδ-fibers convey

fast "picking" pain, punctate stimuli, cold, thermal

Characteristics of Nociceptive C-fibers

UNmyelinated nociceptors; slow conduction; convey slow "burning" and "aching" pain - polymodal (high-threshold mechanical, thermal, cold)

what afferent nerve fibers are nociceptors

Aδ-fibers and C-fibers

what do Nociceptive C-fibers convey

slow "burning" and "aching" pain - polymodal (high-threshold mechanical, thermal, cold)

TRP channels (transient receptor potential)

respond to a number of strong stimuli

what does TRPM8 stimulated by

cool temperature and menthol

what happens when TRPM8 is stimulated by menthol

since TRPM8 responds to both cool temp and menthol - response is same as cold temp

what does TRPV1 stimulated by

capsaicin and noxious heat

what happens when TRPV1 is stimulated by capsaicin

a noxious heat is felt

what kind of surface receptors can nociceptors also express? and what does it lead to

GPCRs and Try receptors - sensitization of the nerve endings

what is allodynia

perception of pain from a normally non-painful stimulus

what is hyperalgesia

exaggerated perception of pain from a normally painful stimulus

where is the Dorsal Root Ganglion (DRG)

spinal cord

ascending pain system

transmits information from nerve endings to the brain (peripheral -> CNS)

Descending pain system

allows the brain to modulate incoming information by sending projections down to the spinal cord (CNS -> peripheral)

what are opioids

Highly effective analgesics

what do presynaptic opioids do

block Ca++ influx; open K+ channels - K+ efflux (leave cell making more negative); decrease excitatory neurotransmitter release

what do postsynaptic opioids do

open K+ channels; hyper polarize 2 degree - order neuron; inhibit action potential generation

what does Acetaminophen do

inhibits COX, But different from NSAIDss

side effects of Acetaminophen overdose

kidney and liver failure

what do NSAIDs do

inhibit COX1 and COX2

what does inhibiting COX enzymes do

stop the process of converting Archidonic acid to Prostaglandins

some notable NSAIDs

aspirin, diclofenac, ibuprofen, naproxen, ketorolac, celecoxib, ketoprofen, and indomethacin

side effects of NSAIDs over usage

nausea, vomiting, diarrhea/constipation, rash, ULCERS, kidney failure, liver failure, and prolonged bleeding

what can aspirin in children and teenagers with chickenpox or influenza do

develop Reye's syndrome - acute pressure in the brain and massive accumulations of fat on the liver

What are the 3 types of opioid receptors

Mu, Delta, and Kappa

Morphine

Mu opined agonist (codeine is less potent morphine)

fentanyl

100 times more potent than morphine

methadone

orally available, long half life

buprenorphine

partial Mu opioid agonist

Pentazocine

Kappa and Mu opioid agonist