With regards to the alpha motor neurone and innervation of skeletal muscle fibres, where is the ACh receptor concentrated?
At the endplate region of the muscle fibre
Which receptors are located at the endplate of the muscle fibre?
Nicotinic ACh receptors
What subunits make up the nicotinic ACh receptor?
2x alpha1
1x beta1
1x delta
1x epsilon
What generates a miniature endplate potential (mepp) at muscle fibres?
One vesicle of ACh activating nictonic ACh receptors at the endplate
What do many successive mepps produce?
Graded epp which, if above threshold, triggers an action potential that will initiate contractions
Once threshold epp is achieved, which channels open to cause an action potential to be fired?
Voltage-gated sodium channels
Which enzyme hydrolyses ACh at the endplate to terminate neuromuscular transmission?
Acetylcholinesterase
Neuromyotonia involves muscle twitches, stiffness, cramps and slow relaxation. How does it arise?
Antibodies produced against K channels in the motor neurone, resulting in repeated firing/hyperexcitation
Which drug blocks Na channels and may be useful in neuromyotonia?
Carbamazepine
Lambert-Eaton Myasthenic Syndrome is associated with muscle weakness and small cell carcinoma. How does it arise?
Antibodies produced against Ca channels causing reduced Ca entry and thus reduced ACh vesicle release (which is needed to initiate muscle contraction)
Which drugs increase ACh concn in the synaptic cleft?
Anticholinesterases (pyridostigimine)
Myasthenia gravis involves muscle weakness during activity. How does it arise?
Antibodies produced againsts nicotinic ACh receptors, causing reduced amplitude of epp and less AP generation
What are the 3 types of pain?
Nociceptive
Inflammatory
Pathological
What is nociceptive pain?
Acute sensory; arises to limit further damage
What is inflammatory pain?
Persistent; outlives initial injury but can heal over time
Which receptors are activated in the presence of noxious stimuli?
Nociceptors (sensory afferents)
Nociceptive pain requires threshold to be achieved to activate nociceptors. True/False?
True
Give an example of heightened pain sensitivity in inflammatory pain
Touching an inflamed joint would be sorer than touching the joint when it is not inflamed
What is pathological pain?
Abnormal nervous system function causes normal stimuli to be felt as noxious
What are the 2 main subtypes of nociceptors?
A-delta-fibres
C-fibres
What is the difference between A-delta-fibres and C-fibres?
A-delta-fibres mediate initial/fast pain; C-fibres mediate the second/aftermath pain
C-fibres conduct faster than A-delta-fibres. True/False?
False
A-delta-fibres conduct faster
Peptidergic polymodal nociceptors are a subset of C-fibres. What are their efferent function?
Release pro-inflammatory mediators from peripheral terminals; contribute to neurogenic inflammation
Peptidergic polymodal nociceptors are a subset of C-fibres. What are their afferent function?
Transmit nociceptive stimuli to the CNS via glutamate and peptides
Axon of primary afferents terminate centrally in the dorsal horn of the spinal cord in various laminae of Rexed. Where do A-delta-fibres and C-fibres terminate?
Laminae I, II
also V for A-delta-fibres
Second order neurones ascend the spinal cord in a system comprised of which two tracts?
Spinoreticular
Spinothalamic
What is the spinothalamic tract concerned with?
Pain perception - where it is, how bad is it
What is the spinoreticular tract concerned with?
Autonomic/emotional response - fear of pain, what can I do to stop it
