Sensory and motor systems, pain and analgesia Flashcards
Whats the basic somatosensory signal transduction pathway?
Physical stimulus -> Mechano- or thermosensitive ion channel in receptor nerve endings -> depolarizes local nerve terminal -> AP fires in sensory nerve cells
What is the molceular mechanism of visual transduction?
Light stimulus -> rhodopsin (GPCR in rod cells) -> retinal isomerised within rhodopsin -> ion channels open , AP fires in optic nerves
What are the roles of the basal ganglia?
- forms a feedback loop to cerebral cortex (adjust motor output)
- Executres pre-programmed motor sequences (voluntary movement)
- Processes proprioceptive sensory input (coordination)
coordination meaning adjusts amplitude and timing of movements Core region of basal ganglia (the striatum) is controlled by an crucial set of dopamine (DA) – containing neurons that project from the substantia nigra.
Striatum is full of dopamine, and when you lose the dopamine neurons you develop tremor : ie Parkinsons
What is the role of the motor cortex?
Evokes muscle contraction directly through control of lower motor neurones.
Composed of the primary motor area, pre-motor area, and supplementary motor area
Only way to govern voluntary movement
Primary: activates movement
Pre-motor: involved in postural preparation for movement
SMA: involved in planning co-ordinated movement
What is the role of the cerebellum? What would happen in the case of cerebellular lesions?
- “damps” movements to prevent overshoot.
- organises sequential movements.
- controls rapid ballistic movements eg typing.
jumbled speech and disordered motor sequence
What neurotransmitter is lost in Parkinsons? Why does the loss result in a tremor?
Dopaminergic neurons in the substantia nigra are degraded
The DA- neurons control the striatum (basal ganglia) so develop a tremor
What afferent neuron carries innocuous sensation?
Ab fibers (large myelinated)
What afferent neurons carries noxious sensations?
aka nocioception
Ad fibers (small myelinated) : first sharp pain
C fibers (unmyelinated): dull throbbing pain
C fibers are the ones associated with chronic pain: They are very vulnerable, and some pateints have these fibres activated very easily (due to bomb blasts or trauma
Where would you find TRPV2, TRPV1, ASIC, TRPA1 channels?
On the dendrites of afferent nocicoceptor neurons (conduct pain to spinal chord)
Eg TRPV1 strongly expressed in small (C-fibre) dorsal root ganglion cells
Where do nocioceptive neurons (Ad and C) project to?
Laminae I and II of spinal dorsal horn
Where do non-nocioceptive neurons (Ab) project to?
Laminae III and IV of spinal dorsal horn
How does peripheral sensation exacerbate chronic pain?
Inflammatory mediators sensitize nerve terminals
ie histamine/prostaglandin
How does central sensation exacerbate chronic pain?
- Local changes in injured nerves and changes in the spinal cord means pain is perceived from wider region than og damage
- Increased involvement of NMDA-type glutamate receptors
- Possible reduction in GABA-mediated inhibitory tone in dorsal horn
active NMDA allows greater influx of Ca2+ so super hypersensitive
Injured nerves can spontaneously fire
What do NSAIDs block? give some examples
- Inhibitors of COX (cyclo-oxygenase) enzymes (COX-1 & COX-2)
- Good analgesics for mild to moderate
inflammatory pain (but not neuropathic pain) - Eg asprin, ibuuprofen, celecoxib
COX enzymes produce the inflammatory mediators – prostaglandins- from a polyunsaturated fatty acid, arachidonic acid
Two distinct COX enzymes produce prostaglandins: COX-1 constitutive, COX-2 induced in pain states
What do opiods block? Give an example
- Bind their GPCR which reduces synthesis of cAMP, inhibits Ca2+ channels, and activates K+ channels
- Eg Morphine (µ), Buprenorphine, Enkephalins
supress input from nocioceptors and activate inhibitory pathways
Opioid receptors are concentrated in brainstem and spinal dorsal horn
