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L15: Pathophysiology of pain
nociceptors, spinal cord, inhibitory mechanisms, pain sensitivities, analgesia
46
Veterinary Medicine
Undergraduate 3
06/01/2012

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Term
Define pain
Definition
an unpleasant sensory and emotional experience, unique to each individual, associated w. actual or potential tissue damage -involves perception of an aversive stimulus - requires capacity of abstraction and elaboration of sensory impulses -stimuli can only be perceived as painful in conscious animals, although the pain pathways may still be active
Term
Define nociception
Definition
refers to neurophysiological manifestations generated by a noxious stimuli - refers to the pain pathways -these pathways can be activated during anaesthesia but they will not be perceived as pain while the animal is unconscious
Term
nociceptors
Definition
free nerve endings of primary order afferent neurones, namely C fibres and Aδ fibres -respond to mechanical, thermal and/or chemical stimuli (may be single or poly-modal), which results in the feeling of pain
Term
Describe the threshold of nociceptors
Definition
-have a higher threshold than other sensory receptors
-show a relative response depending on the amount of stimulation
Term
peripheral afferent fibres - C fibres
Definition
-unmyelinated w. slow conduction velocity -responsible for slower, dull pain
Term
peripheral afferent fibres - Aδ fibres
Definition
-barely mylinated w. a faster conduction velocity than C fibres -responsible for fast, sharp sensation of pain which allows specific localisation of the site of the tissue damage
Term
peripheral afferent fibres - Aβ fibres
Definition
-myelinated, large diameter fibres w. rapid conduction velocity -generally considered to not propagate noxious signals in normal circumstances
Term
SA survey of pain scores
Definition
-orthopaedic surgery deemed most painful
-ovariohysterectomy and castration deemed more painful in dogs than cats - but pain more difficult to detect in cats
-clinicians tend to treat cats less often
Term
spinal cord
Definition
-key role in modulation of noxious info -interaction between sensory neurones in the SC determines which info is relayed supraspinally to high brain centres -key site of action of many endogenous analgesic molecules e.g.opiods, drugs -neurones of the SC receive different types of afferent info e.g. noxious / non-noxious
Term
Specific nociceptive neurons
Definition
-respond only to noxious stimuli -receive input from Aδ and C fibres -involved in coding the location and physical quality of noxious stimuli
Term
Wide range dynamic neurons
Definition
-respond to mechanical, thermal and chemical stimuli -input from C fibres, Aδ fibres and Aβ fibres -code for stimulus intensity - show incr. freq. of response from innocuous to noxious stimuli
Term
Non-nociceptive neurons
Definition
-respond to innocuous stimuli such as low intensity mechanical, thermal and proprioceptive stimuli
Term
pain inhibitory mechanisms
Definition
-spinal cord is an important site of inhibitory mechanisms, to modulate the amount of noxious info that is relayed supraspinally -opiod receptors in the SC are key site on the production of analgesia -descending NA controls from the brainstem and midbrain also act to control nociception
Term
afferent nociceptive pathways
Definition
-projection neurons from the SC form afferent bundles that transmit nociceptive impulses to structures of the brain and diencephalon -different bundles project to different subcortical and cortical structures -glutamte, aspartate, calcitonin gene-related peptide and somatostatin are present in afferent fibers and are released following noxious stimuli - involved in nociceptive transmission
Term
Which cortical and subcortical structures may different afferent nocicpetive pathways transmit to?
Definition
-midbrain
-thalamus
-hypothalamus
-somatosensory cortices
-anterior cingulum
Term
When can nociceptive information be experienced as pain?
Definition
nociceptive info can only be experienced as pain once it has reached the cortex
Term
Cortical projections
Definition
-remember, nociceptive info can only be experienced as pain once it has reached the cortex
-there are 2 systems of nociceptive projection, which act in parallel and complementary manner - lateral and medial systems
Term
Lateral cortical projections
Definition
-participates directly in sensory-discriminitve attribution of nociception -involves specific thalamic nuclei - project to neurons of the primary and secondary somatosensory cortices
Term
Medial cortical projections
Definition
-motivational-affective / emotional component of pain -less defined projections c.f. lateral projections -projections from medial region of thalamus to extensive areas of the primary and secondary somatocortical cortices, including the limbic system
Term
Where is "pain centre" in the brain?
Definition
there is NO specific area in the cerebral cortex that can be identified as a "pain centre"
-the cerebral cortx is described as a "pain matrix"
Term
what changes occur once the pain pathway has been activated?
Definition
-repeated activation of the nociceptive pathway results in heightened sensitivity to pain
-sensations that are normally innocuous are painful
-spontaneous pain in absence of stimulation
Term
What are the 3 categories of pain?
Definition
pain is not homogenous consists of -physiological -inflammatory -neuropathic pain
Term
Physiological pain
Definition
-early warning device - alerts us to the presence of damaging stimuli in the environment - triggers mvmt away -pain is appropriate to the level of stimulation i.e. a stimulus-response relationship is maintained -pain is localised -results from activation of neuroanatomical pathways
Term
Inflammatory pain
Definition
-clinical pain -initiated by tissue damage and inflam. e.g. burn to hand
Term
Neuropathic pain
Definition
-clinical pain -initiated by damage to the nervous system itself e.g. changes in pain pathway
Term
Clinical pain
Definition
-includes inflam. and neuropathic pain
-pain may arise spontaneously
-allodynia
-hyperalgesia
i.e. alteration in stimulus-response relationship
-pain may not be localised
Term
Allodynia
Definition
stimuli that would not normally produce pain begin to do so
e.g.light touch on sunburnt skin
Term
Hyperalgesia
Definition
noxious stimuli evoke a greater and more prolonged pain
i.e. hypersensitive
Term
Plasticity of clinical pain
Definition
-pain pathways are not "hard wired" and are able to change in response to afferent input -plasticity has 2 general forms - modulation and modification plasticity results in heightened sensitivity to pain
Term
Modulation of clinical pain
Definition
reversible changes in the excitability of primary sensory and central neurons -mediated by changes in receptors and ion channels
Term
Modification of clinical pain
Definition
long lasting alterations in the expression of transmitters and ion channels or receptors and cahanges in neuronal structure and connectivity
Term
what causes the changes in pain sensitivity / the plasticity of the NS?
Definition
peripheral and central sensitization
Term
peripheral sensitisation
Definition
-contributes to changes in pain sensitivity -peripheral nociceptor terminals become more excitable so a decr. amount of depolarisation is required to produce an AP discharge i.e. modulation -results in incr. afferent input to the dorsal horn and facilitates spinal excitation
Term
what causes modulation of peripheral sensitisation?
Definition
occurs on exposure of terminal to sensitising agents e.g. inflam mediators (PGE2, 5-HT, bradykinin, leukotrines, histamine) and neurotrophic factors released during tissue damage
Term
What does peripheral sensitisation result in?
Definition
primary peripheral hyperalgesia - hyperalgesia at the site of injury
Term
Central sensitisation
Definition
-enhanced repsonsiveness of sensory neurons, which either outlasts the initiating input or requires a low level drive to maintain it
Term
what causes modulation of central sensitisation?
Definition
-peripheral nociceptor input (C fibres) -activation of the NMDA receptor is key to the development of central sensitisation and enhanced pain sensitivity
Term
What does central sensitisation result in?
Definition
secondary peripheral hyperalgesia - hyperalgesia in the surrounding undamaged tissue
-allodynia
-spontaneous pain
Term
Activation of NMDA receptor
Definition
-not normally activated during physiological pain - key in the development of central sensitisation to pain
-activated only after repeated C fibre activity
-requires glutamate binding, presence of glycine and sufficient depolarisation (caused by repetitive C fibre input) to remove the physiological levels of Mg++ that normally block the channel
Term
What happens once the NMDA receptor channel is opened?
Definition
-Ca++ influx and so massive depolarisation of the neuron
-causes delayed sudden increase in activity
-incr. the amount of noxious input to the SC that is relayed supraspinally to be perceived as pain
i.e. amplification of response, resulting in hyperalgesia, allodynia and spontaneous pain associated w. central sensitisation
Term
Ketamine action
Definition
NMDA antagonist
Term
Pre-emptive analgesia
Definition
-tx initiated before the surgical procedure - decr. the physiological consequences of nociceptive transmission provoked by the procedure -admin of analgesic drugs to prevent the development of peripheral and central sensitisation may be more effective than a similar analgesic given post-op -prevent the incr. sensitivty to pain
Term
Pre-emptive analgesia clinical studies
Definition
so far, studies show pre-emptive admin of analgesics in surgical patients does not have major benefits regarding immediate post-operative pain relief
BUT...
-measuring post-op pain is difficult
-requirements for post-op analgesics is influenced by many factors, not only the degree of pain felt
-pre-emptive analgesia in a clinical setting may not be adequate to prevent sensitisation
Term
Pre-emptive admin of opiods to dogs undergoing ovariohysterectomy has shown...
Definition
... to reduce secondary hyperalgesia
Term
Why has it been decided that pre-emptive/early admin of analgesics is a good thing, despite lack of clinical scientific evidence?
Definition
-no major deleterius effects from pre-emptive analgesia
-intra-op analgesic admin. will decr. the surgical stress response and decr. the requirements for other anaes. agents (i.e. balanced anaes.)
-may confer clinical benefits that can not currently be detected by study designs
Term
multimodal analgesia
Definition
aka balanced analgesia
-using different classes of analgesic drugs in combination
-results in modulation of the pain pathway at different levels and sites - more effective at preventing pain sensation
-some drugs in combo have synergistic effects e.g. alpha-2 agonists and opiods
-allows dec. dose of each drug which may dec. side effects
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