Pain mechanisms Flashcards
What are the 3 forms of pain?
Nociceptive, inflammatory and pathological pain
What is nociceptive pain?
Adaptive - an immediate protective response, short lived
What is inflammatory pain?
Adaptive - assists in healing, persists over days, possibly weeks
What is pathological pain?
Maladaptive - no physiological purpose, persists over months, years or even a lifetime
How is acute pain normally managed?
Generally effectively controlled by NSAIDs, paracetamol and in moderate/severe cases the addition of opioids of several classes
Chronic pain can sometimes be managed by a number of alternative classes of drug such as?
Antidepressants
Anticonvulsants
Local anaesthetics
What kind of pain is not managed well by opioids?
Neuropathic pain
How is pain originating from the skin typically described?
Well localised
Pricking, stabbing, burning
How is pain originating from muscle typically described?
Poorly localised
Aching, soreness, tenderness, cramping, stabbing, burning
How is pain originating from viscera typically described?
Poorly localised
Dullness, vagueness, fullness, nausea
Somatosensory pathways often comprise three neurons in series. Where is the cell body location of the 1st order neuron?
Dorsal root ganglia (innervation of limbs, trunk, posterior head) or cranial ganglia (innervation of anterior head)
Somatosensory pathways often comprise three neurons in series. Where is the cell body location of the 2nd order neuron?
Dorsal horn of spinal cord or brainstem nuclei
Somatosensory pathways often comprise three neurons in series. Where is the cell body location of the 3rd order neuron?
Thalamic nuclei
What are nociceptors?
Specific peripheral primary sensory afferent neurons normally activated preferentially by intense stimuli (e.g. thermal, mechanical, chemical) that are noxious
Nociceptors are first order neurons that relay information to 2nd order neurons in the CNS by chemical synaptic transmission
Nociceptive pain is adaptive and high threshold. What does this mean?
Adaptive - an early warning system to detect and minimise contact with damaging stimuli
High threshold - generally provoked only by intense stimuli that active nociceptors
How does nociceptive pain override most other ongoing activities of the nervous system?
Initiates a withdrawal reflex
Is extremely unpleasant
Engages adverse emotional components
Serves to inscribe memories that allow avoidance of harm in the future
Inflammatory pain is adaptive and protective. What does this mean?
Adaptive and protective - caused by activation of the immune system in injury or infection
Causes pain hypersensitivity (heightened sensitivity to noxious stimuli) and allodynia (innocuous stimuli now elicit pain)
Assists in healing of a damaged body part - pain recedes once this has occurred
Pathological pain is maladaptive. What does this mean?
Results from abnormal nervous system function - may be neuropathic or dysfunctional
What are the subtypes of nociceptor?
A delta fibres
C fibres
What are A delta fibres?
Mechanical/thermal nociceptors that are thinly myelinated - respond to noxious mechanical and thermal stimuli
Mediate first or fast pain
What are C fibres?
Nociceptors that are unmyelinated - collectively they respond to all noxious stimuli
Mediate second or slow pain
What is frequency coding?
The rate of action potential discharge correlates with the intensity of the applied stimulus
What do C-MH fibres respond to?
Noxious mechanical stimuli, activated by noxious heat, sensitive to capsaicin
Shows sensitisation to repeated stimuli
Contributes to heat pain and location of the stimulus
What do C-M fibres respond to?
Noxious mechanical stimuli, insensitive to heat and capsaicin
What do C-H fibres respond to?
Noxious heat, normally insensitive to mechnical stimuli, sensitive to capsaicin
Mediates heat hyperalgesia, does not contribute to precise localisation of stimulus
Acquires sensitivity to mechanical stimulation in the context of inflammation
What do C-MH (silent) fibres respond to?
Normally insensitive to both mechanical and heat stimuli but acquires sensitivity following sensitisation by inflammatory mediators
Sensitive to capsaicin and other algesic, or pro-algesic substances
What do A-MH (type 1) delta fibres respond to?
Require strong mechanical stimuli for activation, activated by noxious heat, insensitive to capsaicin
Show sensitisation to prolonged stimuli
Threshold for activation by heat or mechanical stimuli, drops in the setting of tissue injury
What do A-MH (type II) delta fibres respond to?
Noxious mechanical stimuli and also to noxious heat, sensitive to capsaicin
Shows adaptation
Mediates first pain to heat
What do A-M delta fibres respond to?
Noxious mechanical stimuli, insensitive to heat and capsaicin
What receptors channels are involved in mechanical stimuli?
Receptors/channels have been uncertain despite intense investigation
What receptors/channels are involved in thermal stimuli?
Members of the transient receptor potential (TRP) family, particularly TRPA1, TRPC3, TRPV1 activated by noxious heat
TRPV1 is greatly sensitised in inflammation to become active at body temperature
What receptors/channels are involved in chemical stimuli?
H+ activates acid sensing ion channels (ASICs), ATP activates P2X and P2Y receptors, bradykinin activates B2 receptors
What is the afferent function of peptidergic polymodal nociceptors (subset of C-fibres)?
Transmit nociceptive information to the CNS via release of glutamate and peptides (substance P, neurokinin A) within the dorsal horn
What is the efferent function of peptidergic polymodal nociceptors (subset of C-fibres)?
Release pro-inflammatory mediators (e.g. calcitonin gene-related peptide, substance P) from peripheral terminals - contributes to neurogenic inflammation
What is the role of glutamate in neurotransmission between the primary afferent and second order neuron in the dorsal horn?
Primary transmitter is glutamate producing a fast e.p.s.p. and neuronal excitation by activating primarily postsynaptic AMPA receptors with NMDA receptor participation
What is the role of peptides in neurotransmission between the primary afferent and second order neuron in the dorsal horn?
Peptides (substance P and CGRP) also participate (particularly during high frequency stimulation) causing a slow and prolonged e.p.s.p. that facilitates activation of NMDA receptors by relieving voltage-dependent block by Mg
