BB2

Question 1

1. Suggest potential causes of peripheral pain relevant to this scenario.

Answer 1

Two episodes of pain of different cause:

• Inflammatory, acute pain: this acute nociceptive pain due to muscular strain or other soft tissue injury
• Radicular pain: most common causes are spondylitis/spondylosis (arthritis affecting the joints) or a herniated intervertebral disc related to degenerative conditions of the spine.

Question 2

How do you treat inflammatory, nociceptive pain? [2]

How do you treat radicular / neuropathic pain? [1]

Answer 2

Pain is reduced by the non-
steroidal anti-inflammatory medication and paracetamol.

Neuropathic pain is largely refractory to standard analgesics and requires the use of medications often used in other conditions affecting the central nervous system.

Question 3

Define radicular pain [1]

Answer 3

Radicular pain refers to pain that comes from one single nerve root.

Question 4

Jerry has the following pain:

pain now also radiating down the side of his left leg, across the top of this foot and into his big toe. He says it feels like someone is giving him electric shocks

What vertebral level would the nerve pain be from? [1]

Answer 4

The radicular pain corresponding to that described in Jerry’s case suggests he has
compression of the L5 root from the distribution of shock-like pains which correspond to the distribution of L5 sensory fibres.

Question 5

State the nerve root causing this radicular pain

S1
L5
L4
L3
L2

Answer 5

S1

Question 6

State the nerve root causing this radicular pain

S1
L5
L4
L3
L2

Answer 6

L5

Question 7

State the nerve root causing this radicular pain

S1
L5
L4
L3
L2

Answer 7

L4

Question 8

State the nerve root causing this radicular pain

S1
L5
L4
L3
L2

Answer 8

L3

Question 9

Which is the most common lumbar disc herniation? [1]

Answer 9

Lumbar disc herniation occurs most frequently at L4/L5 (~50%) with L5/S1 herniation just slightly less common (~45%).

Question 10

Alloydyna occurs after which process? [1]

Answer 10

Allodynia appears due to an alteration in the central processing of these innocuous inputs following central sensitisation: noxious inputs drive changes in the
spinal cord that allow innocuous inputs to access the pain pathway to perception.

Question 11

3. Explain why physiotherapy improves the initial condition [3]

Answer 11

A physiotherapist will identify the muscles involved and then design a program of stretching and strengthening exercises, to be done within the limits of pain.

Physiotherapy is suggested because the damaged muscles may have shortened and atrophied, and in severe cases scar tissue may be present.

The muscles need to be loosened and stretched, and this will lessen the pain through increasing blood flow and healing as well as decreasing inflammation

Exercises will help break down the scar tissue in the muscle allowing it to regain its normal flexibility and lessening the chance of further injury.

Question 12

.

Answer 12

.

Question 13

4. How are the electric shock-like and burning pains thought to occur? [3]

Answer 13

Nerve root and/or sensory ganglion compression or irritation occurring:

• This can lead to ectopic neural activity originating from the site of the compression
• Compression can also lead to severing of axons within the nerve roots or spinal nerves, causing inflammatory responses within the nerve which sensitise other cells
• Changes may also take place in the spinal cord at the first synapse and produce spontaneous activity in these central neurons

Question 14

Describe how / why burning pain may occur with Jerry [1]

Answer 14

Burning sensations are often associated with alterations in nociceptor function as a result of injury.

These can result from both peripheral sensitisation (affecting threshold of activation of the sensory neurons themselves) and central sensitisation after injury. The burning sensations that evolve after Jerry’s nerve injury are characteristic of this chronic, neuropathic pain.

Question 15

Explain the MoA of Paracetamol (acetaminophen) [3]

Answer 15

Paracetamol appears to act via at least 2 pathways: it reduces the active oxidized form of the COX-2 enzyme (this form of cyclooxygenase is induced by inflammatory stimuli), preventing it from forming pro-inflammatory substances such as prostaglandins and thromboxanes

Effects on prostaglandin synthesis in the central nervous system are thought primarily responsible for its antipyretic and much of its analgesic actions. One way this occurs is
decreasing prostaglandin E2-induced reduction of glycine inhibition of spinal cord cells

may act through the inhibition of reuptake of endogenous cannabinoids.

Question 16

Why may paracetemol not anti-inflam.? [1]

Answer 16

In the presence of peroxides which are abundant at sites of inflammation, the COX-2 inihibition is inefficient, which appears to explain why it is a poor anti-inflammatory agent.

Question 17

State the class of drugs Diclofenac belongs to [1]

Answer 17

NSAID

Question 18

Explain the difference between diclofenac and ibuprofen [2]

Answer 18

Diclofenac is longer acting than ibuprofen

The additional activity may partly be explained by binding and inhibition of phospholipase A2 and reductions in the substrate arachidonic acid necessary for prostaglandin synthesis (as well as leukotriene) synthesis.

Diclofenac has a low but significant COX-2 selectivity

Question 19

COX-2 selective inhibitors have been associated with higher risk of cardiovascular side effects, including risk of heart attacks and strokes due to inhibition of endothelial prostacyclin without inhibition of []

Answer 19

COX-2 selective inhibitors have been associated with higher risk of cardiovascular side effects, including risk of heart attacks and strokes due to inhibition of endothelial prostacyclin without inhibition of platelet thromboxane A2.

Question 20

Describe MoA of Tramadol [2]

Answer 20

acts at mu opioid receptors but also interacts with monoaminergic systems (inhibits serotonin and noradrenaline reuptake, but less effectivel than TCAs).

Question 21

The most commonly reported adverse drug reactions of tramadol are? [3]

Answer 21

The most commonly reported adverse drug reactions are nausea, vomiting, sweating, itching and constipation.

Question 22

Amitriptyline is which drug class? [1]

Answer 22

TCA

Question 23

Amitriptyline is often prescribed for what type of pain? [1]

Answer 23

neuropathic pain

Question 24

What side effects of amitriptyline are there? [2]

Answer 24

The common side effects that occur from taking amitriptyline are drowsiness and a dry mouth. Many side effects of using amitriptyline are due to its anticholinergic activity.
Adverse effects include: weight gain, changes in appetite, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision, urinary retention.

Question 25

Describe MoA of pregabalin [3]

Answer 25

Its mechanism of action is via binding to the α2δ1 subunit of the N-type voltage gated calcium channels.

These subunits are increased in some neuropathic conditions on nociceptor and other terminals in the spinal cord. Binding of the drug to the subunit leads to a reduction in calcium entry into neuronal terminals

Therefore, pregabalin decreases the release of neurotransmitters such as glutamate, substance P and noradrenaline.

Question 26

Briefly describe how acupuncture is thought to relieve pain [2]

Answer 26

Acupuncture is a form of diffuse noxious inhibitory control (DNIC): hereby pain in one part of the body may reduce pain in all other parts of the body.

Nociceptive input then activates the descending inhibitory neurons in the brainstem reticular formation (periaqueductal gray, raphe nuclei and locus coeruleus)