Neurophysiology + Pain Flashcards
(37 cards)
What is pain?
Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
What is wind-up?
Phenomenon when a repeated stimulus (with no change in strength) causes an increase in response from dorsal horn neurons mediated by the release of excitatory neuromediators
What is hyperalgesia?
Increased pain from a stimulus that normally provoke pain.
Two types - primary and secondary
What is allodynia?
Pain due to a stimulus that does not normally provoke pain; e.g light touch or cold breeze may be perceived as pain.
What is a nociceptor?
Free, unmyelinated nerve ending of a primary afferent neuron (1st order), that depolarises in response to stimuli that are associated with cellular damage and transmits the signal to the spinal cord, where it synapses with a secondary afferent neuron (2nd order)
SNS segment level
T1-L3
PNS emerges from?
CN III, VII, IX and X; and S2-4 sacral segments
Neurotransmitter at preganglionic fibre
SNS + PNS - ACh (nicotinic receptor)
Neurotransmitter at postganglionc fibre/ effector organ
SNS - NA (ACh receptor)
PNS - ACh (muscarinic receptor)
Adrenergic receptors
7 transmembrane segments, coupled to GPCR
A1 (postsynaptic) -> Gq -> activates phospholipase C -> IP3 + DAG
=> Vasoconstriction of blood vessels in skin, GIT, kidney, brain
=> Contraction of SM of ureter, urethral sphincter, vas, uterus, ciliary body
=> Glucose metabolism - gluconeogensis, glycolysis
A2 (presynaptic) -> Gi -> ↓adenyl cyclase -> ↓cAMP
=> Sedation, analgesia, ↓SNS, modulate descending pain pathways
=> Glucose - inhibits insulin release, stimulates glucagon release
=> Contraction of anal sphincter
=> Inhibits NA release
B1 (postsynpatic) -> Gs -> ↑adenyl cyclase -> ↑cAMP
=> CVS - ↑HR, ↑conduction, ↑EF
=> ↑renin release by JG cells
=> ↑hunger
B2 (postsynaptic) -> Gs -> ↑adenyl cyclase -> ↑cAMP
=> SM relaxation - bronchus, bronchiole, detrusor, uterine
=> Contraction of urethral sphincter
=> ↑renin release by JG cells
=> Glucose - inhibits insulin release, stimulate gluconeogensis, glycolysis
B3 -> Gs -> ↑adenyl cyclase -> ↑cAMP
=> Lipolysis
D1 -> Gs -> ↑adenyl cyclase -> ↑cAMP
=> CNS - modulate extrapyramidal activity
=> Vasodilator renal vessels
D2 -> Gi -> ↓adenyl cyclase -> ↓cAMP
=> ↓pituitary hormone
=> Inhibit NA release
Nicotinic ACh receptor effects
Ion channels => changes in cell electrical potential
Activate postglanglionic junctions of both SNS + PNS, + found in NMJ
Peripheral NS
- Transmit outgoing signals from presynaptic to postsynaptic cells within SNS and PSNS
- Receptors found on skeletal muscle that receive ACh for muscular contraction -> EPSP by incr Na+ and K+ permeability
Also found in autonomic ganglia and brain
Muscarinic ACh receptor effects
GPCR (similar to adrenergic receptors), 7 transmembrane configuration
M1, 3, 5 - couples to Gq -> stimulation phospholipase -> ↑IP3 -> ↑DAG -> ↑Ca2+ release from stores -> depolarisation/ ↑excitability
M2,4 - Gi -> ↓adenyl cyclase -> ↓cAMP -> ↓protein phosphorylation -> ↓Ca2+ -> presynaptic inhibitory effect
M1 + M4 - brain
M3, M4 - lung, GIT, glandular tissue
M2 - cardiac tissue
Muscarinic effects
- Bradycardia, salivation, bronchoconstriction, mitosis, incr GIT motility
GPCR - M1 to M5
○ (+) → stimulates the organ, Gq coupled receptor (-) → inhibits the organ, Gi coupled receptor
- M1 (+); M2 (-); M3 (+); M4 (-); M5 (+)
- M1, M4, M5 = CNS 🧠.
- M2 = 🫀
- M3 = everywhere else except for gastric acid secretion (← M1 effect blocked by piperizine for PUD)
Cushing’s Triad
Incr ICP, bradycardia and hypertension
Autonomic dysreflexia/ hyperreflexia
Results from chronic disruption of efferent impulses down the spinal cord, i.e in spinal cord trauma or tumour impingement. More common in lesions above T5.
Stimuli, e.g bladder distention, bowel distention or surgical stimulation -> exaggerated sympathetic response due to loss of normal inhibitory impulses from areas above the level of the lesion.
Sweat glands - receptor and stimulation? Blocked by?
Have muscarinic receptors.
Stimulated by ACh.
Blocked by muscarinic antagonists, e.g atropine or peripheral nerve block
Central control of the ANS?
Mediated in the hypothalamus and medulla oblongata
Saltatory conduction
Where AP can leap from node to node, allowing rapid conduction along axons.
Neurons
Excitable cells; receive, process, integrate and transmit signals
Action potential
Transient reversal of the membrane potential that occurs in excitable cells, including neurone, muscle cells and some endocrine cells.
- Is an ‘all or nothing’ event
Refractory Period
Time following an AP when a further AP either cannot be triggered whatever the size of the stimulus (ARP) or only with application of stimulus of increased size (RRP)
Dorsal column/ medial lemniscal pathway
- Touch, vibration and proprioception
- Ascend ipsilaterally in the dorsal columns to the medulla
=> Synapse in gracious and cuneate nucleus
=> First order neurons extremely long - Second order neuron decussate in medulla and ascend in the medial lemniscus to end in the contralateral ventral posterior lateral (VPL) nucleus
- Third order - then travel to primary somatosensory cortex
Ventrolateral spinothalamic tract
- Mediates pain and temperature
- First order neurons - fibres from nociceptors and thermoreceptors synapse on neurons in the dorsal horn of the spinal cord
- Second order - decussate in the anterior comminsure and then ascend in the ventrolateral spinothalamic tract to the thalamic ventral posterior lateral nucleus (VPL)
Third order - then travel to primary somatosensory cortex
Primary afferents for pain
A∂ fibres
- Myelinated
- 2-5um diameter
- Fast conduction 15-20m/s
- Responds to mechanical and thermal stimuli
- Produce rapid, sharp, well localised pain
C-fibre
- Unmyelinated
- <2um diameter
- Slow conduction 0.5m/s
Respond to mechanical, thermal and chemical stimuli
- Produce dull, poorly localised pain follow A∂ response
Modulation of pain signal
3 mechanisms
- Segmental inhibition (gate control theory)
- Descending inhibition (noradrenergic and serotonergic)
- Endogenous opioid system
Segmental inhibition
- Gate control theory
=> Aß fibres are activated by tactile and noxious stimuli
=> Converge on the same secondary afferent neurons in the substantial gelatinosa as C-fibres
=> Aß fibres activate inhibitory in SG -> decr signals transmitted via C-fibres
Descending inhibition
- Periaqueductal grey area of the midbrain
- PAG => RVLM => dorsal horn in spinal cord => decr transmission by secondary afferent spinothalamic neurons via direct action and also action on inhibitory neurons (use GABA and glycine neurotransmitters)
- Main neurotransmitters are serotonin and NA
- Centrally acting a2 agonists (clonidine), SSRIs and TCAs are thought to have their analgesic effect via this pathway
Opioid system
- Opioid receptor and endogenous opioids (enkephalins, endorphins, dynorphin) are found mainly in PAG, ventral medulla and dorsal horn of the spinal cord
- Opioids can modulate pain transmission at two levels
=> Incr descending inhibition
=> Decr transmission by secondary afferents in the dorsal horn
