Mechanisms of Pain

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  • Created by: LBCW0502
  • Created on: 16-10-18 13:37
What is pain?
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
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What is nociception?
The response of the NS to perceived or actual tissue damage e.g. physiological events associated with delivery of a tissue damaging (noxious) stimulus
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What is noxious stimulus?
A stimulus which is damaging or potentially damaging
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What is transduction?
Conversion of energy of noxious thermal/mechanical/chemical stimulus into electrical energy (nerve impulses) by nociceptors
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What is transmission?
The transmission of neural signals from site of transduction (periphery) to spinal cord and brain
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What is perception?
The appreciation of signals arriving in higher structures as pain
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What is modulation?
Descending inhibitory and facilitatory inputs from brain that modulates nociceptive transmission at the level of the spinal cord
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Describe features of transmission from periphery to spinal cord
Stimulus (chemical/mechanical/thermal). Transduction. Inputs (myelinated/unmyelinated axons/conduction). Cell body in dorsal ganglion of axon. Sensations in CNS at particular areas e.g. laminar 1, 2 etc. Reflexes
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What is the spino-parabrachial pathway associated with?
Emotional component of pain
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What is the Spino-thalamic pathway associated with?
Sensory component of pain (project straight to thalamus)
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Outline the ascending pathway
Spinal cord to brain stem to cortex
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Outline descending limb pathway
Projection from hypothalamus to midbrain (autonomic function) and to the spinal cord (pathway exerts inhibition to acute pain)
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What are the two chemical which mediate transmission between nociceptive afferents (C and A delta) and dorsal horn neurons?
Glutamate (activates AMPA receptors, fast excitatory post-synaptic potentials, NMDA blocked). Neuropeptides (SP acts via NK1 receptor, slow excitatory postsynaptic potentials enhancing glutamate response)
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Outline the mechanism of simple pain transmission (normal condition)
Action potential, release of SP and glutamate, activation of AMPA receptor (NMDA blocked), increase in Ca in neurons, generation of action potential, transformation into multiple identical outputs (input = output), pain perceived at higher levels
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Glutamate exerts excitatory effects via which type of postsynaptic receptors?
Metabotropic/GPCRs (mGluRs) and ionotropic receptors (AMPA or NMDA)
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Outline the process of NMDA receptors at rest (plasticity of spinal cord)
A resting membrane potential, NMDA receptors are blocked by Mg ions. Becomes activated due to increased primary afferent input causing depolarisation of cell. Glutamate enters, Na/Ca ions enter, phosphorylation, neuronal excitability
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Describe features of neuropeptides interacting with receptors in pain transmission
Nociceptors co-release glutamate with excitatory neuropeptides (SP/CGRP). Release of SP enhances action of glutamate (spinal cord/high intensity stimuli). acts at NK1 receptor (expressed on L I-III neurons - specific)
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Outline the gate control theory (1)
Laminar V (converged neuron), input from unmyelinated fibres, nociceptive activation in periphery, leads to activation of WDR, protective mechanism for pain. Nociceptors activate interneurons in spinal cord which inhibits interneuron, more inhibition
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Outline the gate control theory (2)
Ensures that WDR is activated so we feel pain. If activation of large alpha/beta overcomes activation of nociceptor, this leads to activation of interneuron and relief of pain. Gate control in action - counter irritation, TENS
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Describe features of normal/simple state pain transmission
Pain perceived is transcient, reflects the location, duration and intensity of the noxious stimulus
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Describe features of sensitised state pain transmission (sensitisation and plasticity)
Pain perceived outlasts stimulus, response characteristics of neurons change lowering threshold activation. Leads to heightened sensation of pain (hyperalgesia) and perception of innocuous stimuli as painful (allodynia). Involved PNS/CNS changes
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Describe features of sensitised state pain transmission - peripheral
Following tissue injury, inflammation/nerve injury sensitisation of nociceptive pathway is initiated - leads to development of persistent pain. Changes peripherally leads to increased primary afferent input (peripheral sensitisation)
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Describe features of sensitised state pain transmission - central
Changes centrally in dorsal horn excitability changes - central sensitisation
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Describe features of primary sensitisation - peripheral sensitisation (1)
Injury, leads to localised area of primary hyperalgesia (sensitisation of noxious stimuli). Involves C-fibres and produces sensitivity to heat/pressure/impact stimulus
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Describe features of primary sensitisation - peripheral sensitisation (2)
Involves activation/sensitisation of peripheral nociceptors by locally produced inflammatory mediators decreasing the threshold for activation by further stimuli
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Describe features of central sensitisation (physiological plasticity) - (1)
Increase in excitability of CNS neurones triggered by peripheral injury or increased nociceptive input.
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Describe features of central sensitisation (physiological plasticity) - (2)
Manifests in 3 ways - decrease threshold for activation, increase receptive field size and recruitment of novel input, increase spontaneous background activity of neurons. Fundamental to clinical pain - allodynia, hyperalgesia, spontaneous pain
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Outline the basic mechanism for central sensitisation
Action potential, NK1, mGluR, AMPA, increase in Ca, activation of protein kinase etc. phosphorylation of amino acid residues, more Ca (transcription, long lasting, phenotype changes, plasticity, chronic pain, difficult to reverse)-exaggerate output
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Describe features of modulation of pain - endogenous inhibition
Local spinal networks, descending networks from supraspinal sites. Involved GABA receptors, opiods, 5-HT, cannabinoids, results in decreased firing, hyperpolarisation of cell
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Outline the mechanism for endogenous inhibition
Terminal of afferent fibre (CB, GAB, 5HT - also expressed in projection neuron). Inhibition/reduced release of SP/glutamate, reduced activation/inhibition of projection neuron, reduce Ca levels, little postsynaptic output
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What increases serotonin and noradrenaline levels?
Antidepressants - need to be taken for weeks before efficacy is shown
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What is the function of analgesics e.g. morphine?
Inhibits ability to feel acute pain (anti-nociceptor drug - establish normal thresholds)
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Other cards in this set

Card 2

Front

What is nociception?

Back

The response of the NS to perceived or actual tissue damage e.g. physiological events associated with delivery of a tissue damaging (noxious) stimulus

Card 3

Front

What is noxious stimulus?

Back

Preview of the front of card 3

Card 4

Front

What is transduction?

Back

Preview of the front of card 4

Card 5

Front

What is transmission?

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