Neuroscience CA2

Að

Fast pain fibres

C

Slow pain fibres

6-30m/s

Conduction velocity for fast pain fibres

0.5-2m/s

Conduction velocity for slow pain fibres

Pain fibres

What are the 1st order neurons in the nociceptive pathway?

Dorsal horn neurons

What are the 2nd order neurons in the nociceptive pathway?

Glutamate

What is the neurotransmitter between Að fibres and DHNs?

Glutamate or substance P

What is the neurotransmitter between C fibres and DHNs?

Peripheral sensitisation

When peripheral C and Að fibres show spontaneous activity and respond to weaker stimuli

Central sensitisation

Secondary changes in the spinal cord due to increased glutamate release from C and Að fibres bombarding DHNs

NMDA

What receptor type expression is increased in the spinal cord in central sensitisation?

Aẞ (mechanoreceptors)

What receptors do damaged pain fibres sprout?

Body’s own pain relieving pathway

What is stress analgesia?

PVN neurons

What neurons in the hypothalamus are activated in stress analgesia?

Periaqueductal grey → raphe magnus nucleus → inhibitor interneurons

Where are signals from the PVN relayed to in stress analgesia ?

GABA and enkaphilns

What is released by inhibitory interneurons to prevent pain signals travelling to the 2nd order neurons?

Opioids

Drugs that inhibit pain signals at the spinal cord by activating opioid receptors and the descending pathway by removing GABA inhibition of PAG

Morphine, pethidine, codeine

Examples of clinically used opioids (3)

NSAIDS

Drugs that reduce allodynia associated with inflammation by inhibiting prostaglandins and thromboxin A2 production by inhibiting cyclooxygenase

Ibuprofen, aspirin

Examples of NSAIDS

Local anaesthetics

Drugs that block the initiation and propagation of APs by pain fibres

Lidocaine

Example of a local anaesthetic

Ionised

What form of local anaesthetic has to penetrate Na+ channels in their open state ?

Unionised

What form of local anaesthetic can easily cross the plasma membrane and pick up a H+to block the Na+ channel?

With each AP there is more opportunity for the ionised form to enter and block the Na+ channels so depth of block is increased with each AP

What is a use-dependent block?

ACh receptor (muscarinic)

Receptor type for parasympathetic nerves

Gi (inhibitory)

What G-protein is linked to receptors M1,M3 and M5?

Gq (facilitatory)

What G-protein is linked to receptors M2 and M4?

Decrease cAMP by inhibiting adenyl cyclase. Less cAMP = Ca channels open for shorter

How do Gi linked receptors inhibit contraction?

Increase IP3 and DA production which increases K channel condyctance and stimulates Ca release. Cells easier to stimulate and more Ca

How do Gq linked receptors increase contraction?

M2 (cardiac) and M3 (smooth msucle)

Which muscarinic receptors do clinical useful drugs a act on?

Glaucoma and bladder hypomotility

What do muscarinic agonists treat? (2)

Pilocarpine

Muscarinic agonists that treats glaucoma by causing pupil constriction

Bethanecol

Muscarinic agonist that treats bladder hypomotility by increasing parasympathetic activation

Incontinence, asthma and GI hypermotility

What are muscarinic antagonists used to treat? (3)

Atropine

Musacarinic antagonist that is an antispasmodic

Oxybutynin

Muscarinic antagonists that treats urinary incontinence

ipratropium

Muscarinic antagonists that treats asthma by relaxing bronchi

Adrenoceptors

What type of receptors do sympathetic nerves have?

A1, A2, B1, B2

Types of adrenoceptor (4)

Gq

What G protein is. Linked to A1 receptors?

Gi

What G protein is linked to A2 receptors?

Gs

What G protein is linked to B1 and B2 receptors?

Increase cAMP production

How do Gs linked receptors increase contraction?

Adrenaline

Example of an A and B adrenoceptor agonist That increases vasoconstriction and heart rate

Doxasosin and prazosin

Examples of an A1 antagonist that are used as antihypertensive drugs (2)

dobutamine

Example of a B1 agonist that is used to treat heart failure

Salbutamol and salmeterol

Examples of a B2 agonist that is used to treat asthma (2)

Propranolol

Example of a B receptor antagonist that is used to treat panic attacks

Atenolol

Example of a B1 receptor antagonist that is used to treat hypertension

ACh (nicotinic)

Receptor type at the ganglia for parasympathetic and sympathetic nerves

Nicotine and varencline

Agonists of the nicotinic ganglion type receptor used to help quit smoking

Significant side effects. Removal of all autonomic activity

Why are there no clinically useful nicotinic ganglion type antagonists?

Nicotinic

What is the only type of receptor at the NMJ?

Muscle contraction

What do nicotinic agonists cause initially?

Suxamethonium

Example of a nicotinic agonist used in surgery

Depolarising blocking agent (depolarises then relaxes)

What type of agent is suxamethonium?

Tubocurarine and pancuronium

Examples of a competitive nicotinic antagonist used in surgery (2)

Non-depolarising blocking agents (prevent ACh mediated muscle contraction)

What type of agents are tubocurarine and pancronium ?

Anticholinesterases

What inhibits cholinesterase enzymes and reduces ACh breakdown ?

Neostygmine and pyridostigmine

Examples of nit cholinesterase that treat myasthenia gravis and reverse NM block after surgery (2)