Pain Mechanisms Flashcards
What do nociceptors respond to?
Most are polymodal
- mechanical
- thermal (hot and cold)
- chemical (dissolved chemicals
Silent/sleeping nociceptors - only respond in presence of inflammation
Nociceptor
- location
- function
Visceral Muscle, bone, connective tissue Cutaneous -Ad - cold thermoreceptor -C - warmth thermoreceptor
Convert noxious stimuli => electrical energy
-inflammatory biochemicals sensitise nerve endings
Peripheral sensitisation
-how does this occurs
Inflammatory response => reduced threshold, increased responsiveness of peripheral nociceptor ends
Primary hyperalgesia - sensitisation of the damaged area
Secondary hyperalgesia - sensitisation of the area around the wound due to central mechanisms
Allodynia - non noxious stimuli trigger peripheral nerve endings
Transmission
-route
Nociceptor nerve end => Ad/C fibre => cell body in DRG => 2nd order neuron in DH => decussate and enter spinothalamic tract
Fibre types
-characteristics
Ad - mechano/thermo nociceptors
- myelinated
- fast, sharp localised pain during 1st signs of injury
C - polymodal nociceptors
- unmyelinated
- slow, diffuse, dull aching that continues to remind you of the injury
Neurotransmitters
- types
- action
- receptor
- site
Glutamate (E)
- AMPA, NMDA, metabotropic glutamate
- C
Substance P (E)
- NK1
- C
Calcitonin gene related peptide (E)
- CGPR
- Ad, C fibres
Seretonin (E in PNS, I in CNS)
- 5HT
- C+P
GABA (I)
- GABAa, b
- C
Brain areas involved in pain processing
Thalamus - relay stimuli to different areas of the brain
Limbic - emotional response
-sandwich the thalamus
Temporal - learning and memory
Somatosensory cortex in frontal and parietal lobe
- focus attention on pain => difficulty concentrating on other things
- executive functions => modify behavioural and emotional response to pain in response to a situation
Modulation
-descending inhibitory pathways and their effects
Transmission can
- facilitate
- amplify
- inhibit pain experienced
Descending modulating inhibitory
- GABA, NA, S
- endogenous opioids act on CNS opioid receptors (enkephalins, endorphins, dynorphins)
Cognitive processes - distraction, relaxation techniques
Other nervous inputs - SNS response, sensory stimulation via Ab fibres
Modulation
-descending excitatory pathways and their effects
Anxiety, fear, depression => increase pain
-important to address these areas to reduce pain experienced
Central sensitisation
Increases excitability of the neurons in the CNS => alters strength of synaptic connections
Continuous firing of C fibres => Increased release of glutamate => activates NMDA receptors => increased protein synthesis and gene expression => increased neuronal density, sensitivity, strength of response and spontaneous firing
Increases risk of the development of neuropathic pain
Neuropathic pain
- causes
- characteristics
Peripheral nerve damage
-lesion, demyelination, compression, cutting, tearing
Dysfunction of nervous system due to plasticity of CNS
May not always have an identifiable cause or be related to a medical or degenerative condition
No protective function with no association with noxious stimuli or causal events
Intensity unrelated to stimuli
- stabbing, shooting, burning, paresthesia
- allodynia
- hyperalgesia
Cellular and molecular changes in neuropathic pain
-changes and consequences
Central sensitisation => allodynia, hyperalgesia
- activation of NMDA, increased no and altered function of NaC
- normal inhibitory controls reduced
DH neurons less sensitive to inhibition
Inhibitory interneurons may die
Seretonin increases signals instead of inhibits them
Net balance between inhibition and facilitation disrupted
Vital that we treat nociceptive pain effectively to prevent neuropathic pain from developing
Aims of neuropathic pain treatment
Focus on reducing pain
Individualise goals that aim to minimize impact of pain and improve QOL
Multimodal, multidisciplinary approach
