Pain Flashcards
types of pain
- neuropathic
- nociceptive
neuropathic pain: define
- pain initiated by primary lesion or disease in PNS or CNS
nociceptive pain: define
- non/inflammatory response to noxious stimulus
neuropathic pain: eg
- pinching of nerves (sciatica)
- nerve trauma
- infection
nociceptive pain: features
- protective mechanism for awareness tissue damage occurring/ may happen
may be accompanied by:
- reflexive withdrawal from stimulus
- autonomic response (increase BP)
- emotional responses (fear, anxiety)
nociceptive pain: for pain transmission
- ascending pathways
nociceptive pain: for pain modulation
- descending pathways
nociceptors: types of free nerve endings and for?
- mechano (intense physical)
- thermo (intense hot/cold)
- chemo (noxious endogenous/ exogenous chemicals, inflammatory mediators)
- polymodal (intense mechanical, thermal, chemical)
nociceptors: free nerve endings found
- skin
- mm, joints
- internal organs
nociceptors: vs non-nociceptive receptors
- no spontaneous/ background firing of APs
- relatively large receptive fields
- slow adapting/ non
- high threshold
- sensitised by intense/ prolonged stimulation
- glutamate and substance P onto 2˚ neurons
non-nociceptors bs nociceptors:
- spontaneous firing (resting level of AP generation)
- low threshold (high sensitivity)
- small/ large receptive fields
- fast/ slow adapting
- mostly release glutamate
nociceptors: fibre types name
- A delta
- C fibres
nociceptors: fibre types features
- A fast (mechanical/ thermal pain receptors) - myelinated
- C slow (polymodal receptors) - non-myelinated
- differences in conduction velocity generate ‘double pain’ sensation
nociceptors: cutaneous mechanical
- first pain after mechanical injury
- A delta fibre
- pricking, stabbing
nociceptors: cutaneous thermal
- fast pain via A delta fibres
- intense thermal stimuli (>45˚ and <10˚)
- temperature sensitive TRP ion channels
nociceptors: cutaneous polymodal
- second pain
- thin C type fibre
- slow burning, throbbing
- slow/ no adaptation
- intense mechanical/ thermal/ specific chemical (capsaicin, H+)
nociceptors: cutaneous polymodal- substances released responding to tissue damage
mechanical:
- K, H+, ATP, acetylcholine, substance P
damaged blood v: bradykinin
mast cells: nerve growth factor, histamine
damaged blood platelets: serotonin
nociceptors: visceral
- free nerve endings
- mechano and chemo
- pain diffuses and difficult to locate
nociceptors: visceral eg
- excessive distention of organ
- infection in digestive/ renal
- cancer
- (lack of blood supply)
- inflammation
tissue damage causes release of substances:
- ATP
- H+ ions
- K+ ions
- prostaglandins
substances released in tissue damage act:
- directly on ion channels
- bind to metabotropic receptors (G proteins, 2˚ messengers)
- depolarise nociceptors
axon reflex/ neurogenic inflammation: features
- depolarisation of nociceptor primary afferent endings
- generator potential spreads to trigger zone generating APs that:
- spread centrally to synapse w 2nd order = pain signal in spinal cord
- spread peripherally (antidromically) along sensory endings = axon reflex
axon reflex is very few eg of
- neural reflex not involving at least one neuron in CNS
axon reflex causes release of:
- neuropeptides (sub P) from afferent endings
axon reflex/ neurogenic inflammation: sub P causes
- vasodilation at site (redness)
- mast cells -> histamine -> swelling of surrounding tissues (edema)
- further stimulation/ sensitisation of nociceptors
afferent pain pathways:
- 2nd order neurons ascend to thalamus via lateral spinothalamic tract (ALS)
- collaterals travel to reticular formation for ‘low level’ response
convergence projection theory of referred pain:
- visceral sensory afferents run in same n bundle as somatic sensory afferents
- also share some 2ndary neurons in spinothalamic pathway
- severe visceral pain referred to dermatome
pain transmission and pain perception: influenced by
- past/ present experiences:
- gate control theory of pain
- descending pathways (eg. endogenous analgesia system)
- sensitisation
gate control theory of pain: what is it
- transmission of pain signals to brain modulated by mechanical stimulation (rubbing skin around painful area) or electrical stimulation (TENS machine)
gate control theory of pain: involves
- A beta fibre collaterals from cutaneous mechanoreceptors excite inhibitory interneurons (GABAergic/ glycinergic) in spinal cord/ brainstem
- suppress transmission of pain signals (delivered by C fibres) inhibiting 2nd order neurons)
gate control theory of pain: TENS
- trans cutaneous electrical nerve stimulation
- mimic stimulation of skin mechanoreceptors
- targets large myelinated A beta fibres reducing C fibre transmission
descending pain pathways:
- limbic system involved in affective (mood) aspects of pain (fear, sleep, hunger, temp)
- limbic system sends efferent fibres to spinal cord affecting balance of activity in dorsal horn
- inhibitory efferents (release noradrenaline/ serotonin) inhibition - reduce pain
- excitatory efferents (release serotonin) facilitation - enhance pain
endogenous analgesia:
- response to stressful situations -> suppress transmission of pain signals
- descending pathways from midbrain periaqueductal grey matter via medulla to spinal cord
- release endogenous opioids (enkephalin) onto synapse btw primary nociceptor afferents
endogenous analgesia: effect of endogenous opioids
- presynaptic inhibition of sub P release from C fibres (primary pain afferent)
- postsynaptic inhibition by generation of IPSPs in 2nd order neuron
sensitisation:
- inflammation/ tissue damage causes sensitisation
- in periphery (receptor endings)
- in CNS (at synapse w 2nd order neurons)
- increase sensitivity (Vm closer to threshold for AP) lower threshold to pain
sensitisation: hyperalgesia
- abnormally heightened sensitivity to noxious stimuli
sensitisation: allodynia
pain sensation responding to usually non-painful stimuli (touching, cooling/ heating)
peripheral sensitisation: features
- release of inflammatory mediators (NGF, bradykinin (BK), prostaglandins (PGE))
- activate intracellular kinases (PKA, PKC)
peripheral sensitisation: kinases cause
- phosphorylate membrane receptors
- decrease threshold of transducer channels
- increase excitability of voltage gated Na channels (generate more APs)
- hyperalgesia
- allodynia
eg. sunburn
- release prostaglandin sensitises TRPV1 channel
- warm shower is painful following
central peripheral sensitisation:
- prolonged pain (inflammation)/ brief intense pain trigger changes in CNS resemble underlying peripheral sensitisation
- prolonged/ intense release of glutamate from primary nociceptor afferent n terminals onto dendrites of 2ndary afferent n in response
cell increasingly excitable
- allodynia
- hyperalgesia
- 2ndary hyperalgesia (spread of sensitivity to non-injured areas)
central sensitisation: immediate
- glutamate activates AMPA and NMDA (postsynaptic membrane)
- NMDA receptors activated (Mg expelled)
- NMDA receptors allow Na influx (depolarisation) and Ca influx (kinase activation)
central sensitisation: immediate - kinase activation leads to
- phosphorylation of NMDA receptor proteins
- insert more NMDA receptors in membrane
- NMDA receptors stay open longer
- increased excitability of 2ndary afferent neurons - more pain
central sensitisation: delayed/ late onset
- neuroactive substances release by inflammatory cells into CSF
- eg. cytokines like IL - 1beta
- IL 1beta promotes activity of Cox2
- Cox 2 generates prostaglandin E2
central sensitisation: delayed/ late onset PGE2 effects
- facilitate synaptic transmission
- increase excitability of neurons
- reduce inhibition by inhibitory interneurons
- structural changes in synaptic connectivity
- more pain
analgesia: local anaesthetic eg
- lidocaine
analgesia: local anaesthetic lidocaine
- blocks voltage gated sodium channels
- prevents firing of AP by nociceptive primary afferents
analgesia: systemic analgesics eg
- aspirin (acetylsalicylic acid)
- opioids
- NMDA antagonists/ Cox2 inhibitors
analgesia: systemic analgesics aspirin
- arachidonic acid released by cellular damage converted to prostaglandins and cytokines
- prostaglandin blocks K from nociceptors - enhance depolarisation in response to stimulus (more AP)
- aspirin blocks converse - reduce firing by nociceptors
analgesia: systemic analgesics opioids
endogenous analgesia
analgesia: systemic analgesics NMDA antagonists and Cox2 inhibitors
central sensitisation
