Lecture 14 - Pain Flashcards
(30 cards)
pain =
nociception
Pain receptors
Receptors are axon endings without obvious anatomical specialisations, found everywhere in the body - except brain.
Broad receptive fields, bare nerve endings, multiple branches spreading out in the skin - does not give precise location of pain, use other sensory modalities to tell us precisely where the injury has occurred
Different endings respond to strong mechanical stimuli, and/or high temperatures, chemicals (that are released in damaged tissue)
[some exogenous chemicals activate receptors directly, e.g. capsaicin, menthol]
Things that have the potential to cause injury are responded to
When you overactive pain fibres they stop responding
Pain is used to
Pain is useful to avoid injury, alert us to local infection, or aid recovery, but can become chronic or spontaneous, and can indicate disease elsewhere in the body.
No pain would not be ideal
Pain is carried by
two types of nerve fibres - C fibres and A delta fibres
“C”- fibres
“C”- fibres
Smallest diameter, unmyelinated axons
Slow conduction velocity (they do not need to be as efficient in bringing information into the nervous system
Signal ongoing damage (or potential damage) (longer duration of pain)
“A𝜹”-fibres (A delta fibres)
“A𝜹”-fibres (A delta fibres)
Small diameter myelinated axons
Faster conduction velocity
Signal acute onset of painful stimulus
Sensation in pain pathways
Sensation can change over time
Pain pathways become more sensitive (hyperalgesia - increased pain sensitivity locally) following injury, or inflammatory disease (e.g. arthritis).
Injury site and area around injury become ‘tender’
Pain pathway sensation can change due to
Sensitisation of sensory endings by locally released factors (become more sensitive to changes in the environment, fire more action potentials, easier to get to threshold from smaller inputs because of factors released by the tissue locally
Changes at CNS synapses
Hyperalgesic area
enderness, sensitised neighbouring axons are present here
K+ in pain perception
K+ - cell breaks, intracellular contents comes out, potassium levels rise and axons locally will get close to threshold because the equilibrium potential of K+ changes therefore more likely to generate action potentials i.e. more action potentials in pain fibres due to local tissue damage
Bradykinin, 5-HT (serotonin) and prostaglandins in pain perception
Bradykinin, 5-HT (serotonin) and prostaglandins - all of these molecules especially prostaglandins are associated with the clotting mechanism (participate in platelet aggregation for clotting) but they are also involved in activating pain fibres, these local factors are released by damaged tissue that can increase the sensitivity of pain fibres locally
Mast cells in pain perception
Mast cells = filled with granules that contain histamines, histamines spreadings out from the mast cells recruits neighbouring axons to bring them closer to threshold. Now in a situation where there has been a local injury, local doctors released that activate pain fibres that feedback into the system’s chemistry that activates surrounding pain fibres that makes them more likely to be activated by any other inputs so the injury may initially have been very small but now the surrounding areas are sensing painful signals to the brain
Substance P, CGRP in pain perceptions
Substance P, CGRP - released from pain fibres to activate other cells like mast cells which release histamines which in turn gives positive feedback on to the nerve terminals themselves (local inflammatory changes feeding into increased pain sensation)
Histamines in pain perception
Histamines are also involved in the allergic reaction
Give the itch sensation
Aspirin in pain perception
Aspirin = inhibitor of prostaglandin synthesis which are involved in clotting therefore it is a anticlotting agent and a analgesic (pain reliving medication)
Long term changes in pain perception
The long term changes in synapse strength requires plasticity to do this
Long term changes in synapse strength, modulation by descending pathways
Another way of increasing sensitivity
Another way of increasing sensitiby would be to increase the efficiency of the synapses in the anterolateral pathway
Pain control
Inhibition of pain pathways
“Gating” of pain impulses by non-painful stimuli of nearby nerves
Inputs from nearby non-pain nerves inhibits responses of ascending pain fibres
e.g rubbing affected area - activates non-pain fibres to stop responses in pain fibres
Trans-epidermal nerve stimulation (“TENS”)
Descending control - pathways to spinal cord from brain and brainstem also regulate pain transmission
Anterolateral pathway function
pain, temperature, some touch (enters spinal cord and crosses straight away)
Gate model
A fibres carrying sensory input - mechanoreceptors raise threshold (close gate), C fibres carrying pain signals
Inhibitory signals from the brain
Interaction between stimulating and inhibiting signals (gate)
Pain intensity depends on modulation at gate
Pain control - endogenous opiates
Endogenous opiates: released at synapses on pain-pathway neurons “natural analgesia” system, acute response to pain, stress. site of action of ‘centrally acting’ painkillers (morphine, codeine). [Activated by acupuncture ??]
Painkillers activates receptors and it also decreases the postsynaptic excitability of pain fibres taking information up to the brain
Pain control - endocannabinoids
Endocannabinoids. Synthesised and released by neurons (but not stored in vesicles i.e. lipophilic). Decrease long-term sensitivity to pain, act on pain receptors, as well as centrally. [Mediate some presumed effects of endogenous opiates ??]
What can the brain do about pain perception
There is a lot the brain can do about pain perception … Arousal, placebo (nocebo= say bad side effects, more likely to report them as a result), anxiety, association, suggestion………….
peripheral neural pathways, descending pathways from several brain regions, and various chemical transmitters (in addition to opiates and cannabinoids) can modulate pain//can inhibit or facilitate perception and modify responses to pain
Diabetic neuropathy
(Beginning) Tingling or burning in toes, feet, legs, fingers, hands, or arms
Tingling is a result of action potential sequences/patterns of information arriving in the brain that it cannot really interpret it in a way that is meaningful (action potentials are not in the right frequencies/sequences)
A “pins and needles” feeling (more extreme tingling)
Pain or cramping
Numbness or loss of sensation
Action potentials are no longer propagated in particular fibres, start beginning in periphery
Insensitivity to heat and cold
Extreme sensitivity to even the lightest touch
Neurons become more likely to fire because metabolism is starting to become disordered so may try to express additional ion channels on the surface to increase sensitivity
Muscle weakness in hands or feet
(Extreme) Loss of coordination or balance that makes it harder to walk
The effect motor axons which tend to have a larger diameter and tend to be more robust
[can also include multiple autonomic dysfunctions, effects on retina]
(Ultimately) Loss of sensation, including pain, leads to tissue damage (may lead to amputations)
