sensory/opioids

Question 1

Outline the MOA of opioids (morphine)

Answer 1

-Morphine binds to its Gi PCR (Mu)
-Inhibits adenylyl cyclase
-increases MAPK
-Opens K+ channels -> K+ efflux -> hyperpolarisation
-inhibits opening of calcium channels.

Hyperpolarisation + No calcium inhibits action potential propogation + NT release.

At spinal level, morphine achieves analgesia in 2 ways:

(1) Presynaptically: it inhibits release of NT from first order neuron into dorsal horn’s synaptic cleft.

(2) inhibits excitation of the 2nd order neuron in synaptic cleft

-Also inhibits GABA releasing neurons within the periaqueductal grey matter -> disinhibition of the inhibitory descending pathway from PAG -> further adds to analgesia by activating the “gate” response.

Therefore there is no relay of nociceptive signals any further beyond this point.

Question 2

Describe the structure of morphine

Answer 2

2 planar rings
2 aliphatic rings
free hydroxyl group on benzene ring attached to nitrogen via 2 carbons -> this gives it it’s opioid activity.

Substitution of hydroxyl group can give variants of morphine e.g. codeine, diamorphine, oxycodone

Question 3

Outline the Gate control theory of pain modulation

Answer 3

The gate control theory proposes that pain signals entering the dorsal horn of the spinal cord can be modulated by inhibitory interneurons in the substantia gelatinosa.

These interneurons can release inhibitory neurotransmitters, such as GABA, which prevent the activation of second-order neurons, thereby inhibiting the transmission of pain signals to the brain.

This modulation is influenced by the relative activity of large-diameter (non-painful) and small-diameter (painful) nerve fibers. Activity in large-diameter fibers can inhibit pain signals by enhancing the inhibitory action of these interneurons

Question 4

Describe the descending/supraspinal modulation of pain in the spinal cord

Answer 4

Endogenous opioids, encephalin and endorphins, bind to opioid receptors in the periaqueductal grey matter (mdibrain) and rostral ventromedial medulla (medulla).

This binding results in disinhibition of inhibitory GABA’ergic interneurons leading to activation of monoaminergic descending pathways to the dorsal horn of the spinal cord to inhibit the transmission of pain impulses from nociceptive activation.

Question 5

damage above what spinal cord level can result in neurogenic shock? What are the 3 signs

What type of shock does it cause

Answer 5

Above T6.

1. Hypotension due to loss of norepinephrine to vessels and unopposed parasympathetic innervation to vasculature
2. Bradycardia - same reason
3. Hypothermia

Can cause distributive shock due to the hypotension causing reduced pre-load and inability of the heart to counteract this by beating faster.

Treat with atropine to bring up HR and vasopressors to bring up BP

Question 6

micturition phases and the nerves involved

Answer 6

Filling - SNS - hypogastric
Voiding - PSNS - pelvic splanchnic
Somatic (for both) - pudendal

Question 7

what is the difference between nociception and pain

Answer 7

Nociception refers to the body’s ability to detect changes in the environment/noxious stimuli which are causing or may causing actual tissue damage.

Pain refers to the subjective experience of actual or impending harm, usually but not always following nociceptive stimulation.