Year 2 Case 10 ILOs

Why do we image the CNS

• Confirm clinical diagnosis

• Rule out serious conditions

• Aid prognosis/guide treatment

What may be missed on imaging

• Raised ICP

• Cerebral venous sinus thrombosis

• Stroke

• Subarachnoid haemorrhage

Anything involving neuromuscular system

advantages of MRI

• Does not use ionising radiation or x-rays

• Used for viewing soft-tissues and tendons

More detailed

disadvantages of MRI

• Expensive

• Patients must remain completely still

• Patient cannot have metal

  • Those with kidney issues or pregnant may not tolerate the contrast needed

advantages of fMRI

• High resolution

• Psychological evaluation

Does not use ionising radiation or x-rays

advantages of CT scan

• Detailed imaging of whole body

• Faster

Less restrictions so more patients can have them

disadvantages of CT scan

• Exposure to radiation

Contrast material risks

advantages of PET scan

• High resolution

Versatility

disadvantages of PET scan

• Radiation exposure

• Contrast material risks

• Less availability

Preparation takes longer

what is radiculopathy

compression or irritation of spinal nerve root, causing pain with sensory changes and/or motor changes

what is radicular pain

only pain, no other symptoms

most common cause of sciatica

The most common cause is a herniated disc which occurs due to degenerative changes, specifically L4-S1 roots.

Aetiology of sciatica

• Each spinal nerve has a dorsal (sensory) and ventral (motor) root

• These can be compressed or irritated due to trauma or a degenerative process, causing edema, ischemia and inflammation

This can cause radicular pain or radiculopathy depending on if both or one of the root fibres are affected

Causes of lumbar radiculopathy

• Herniated disc

• Spinal stenosis

• Spondylolisthesis

• Pelvic or lumbar fractures (lead to nerve avulsion or ruptured)

• Cancer

Infection

risk factors for lumbar radiculopathy

• Modifiable: smoking, obesity, strenuous physical activity, whole body vibration

Non-modifiable: age, history of back pain, variations in intragenic vitamin receptor gene (predisposed to degenerative disc disease)

clinical features of lumbar radiculopathy

• Radiating pain that spreads distally from lumbar spine

• Pain is usually unilateral but can be bilateral

• Sensory changes: numbness, paraesthesia

• Motor changes: paresis (weakness), loss of strength/ power

• Pain worsens during movement especially after long periods of inactivity

• Worsened by sneezing or coughing

imaging in lumbar radiculopathy

• MRI- identify disc herniation

• XRAY- spinal injury or assess degenerative joint changes

Electromyography and nerve conduction tests-determine which roots are affected and how much

Conservative management of lumbar radiculopathy may consist of:

• Patient education: advice about how to avoid pain triggers (such as prolonged sitting), information leaflets for supported self-management, and reassurance (e.g. ‘‘…most uncomplicated cases of sciatica self-resolve within 12 months…’’)

• Lifestyle modification: ask the patient about their occupation and activities of daily living (ADLs), and consider any reasonable adjustments (e.g. warehouse workers may need modified duties or time off work to allow symptoms to ease)

• Medication: over-the-counter analgesia such as paracetamol and NSAIDs (with gastroprotection), unless contraindicated. Also consider prescription oral analgesics (e.g. codeine)

• Referral to musculoskeletal physiotherapy for exercise guidance and lifestyle modification

• Referral to psychological services (e.g. behavioural therapies) as part of a multi-disciplinary approach if indicated (e.g. if radiculopathy is causing problems with mental health, impacting the ability to work or fulfil social roles)

Surgical management may be indicated in some cases of sciatica, for example

• When conservative management fails beyond the normal trajectory

• When symptoms are intractable

• When radiculopathy is caused by a serious pathology

• When the patient has severe neurological deficits (e.g. a new foot drop)

common surgical procedures used for sciatica

• Discectomy

• Spinal decompression

• Open laminectomy with discectomy

• Microendoscopic discectomy (MED)

what is a discectomy

Removal of part of the intervertebral disc that is compressing the nerve.

what is laminectomy

Removal of part of the lamina to create more space for spinal nerves.

what is a spinal fusion surgery

Joining two or more vertebrae to stabilize the spine.

what is a foraminotomy

Enlarging the neuroforamen to provide more room for the nerve root.

what is a facetectomy

Removing bony overgrowth to relieve nerve root compression.

People with lumbar radiculopathy may develop the following complications:

• Pain: causes reduced functional mobility, loss of independence, the inability to fulfil social or occupational roles, and decreased health-related quality of life

• Central sensitisation or nociplastic pain if clinical features persist

• Muscle atrophy and deconditioning, exacerbating loss of function

• Progressive limb weakness and major motor radiculopathy

• Cauda equina syndrome: which can develop secondary to lumbar radiculopathy, and must be investigated immediately

Causes of cauda equina syndrome

• Birth defects of spina cord (spina bifida)

• Infection of meninges

• Abscess or tumour pushing on cauda equina

• Spinal cord injury

• Spinal stenosis

Arteriovenous malformation

Symptoms of cauda equina syndrome

• Reduced sexual response

• Retention of urine

• Loss of bladder control

• Loss of bowel control

• Loss of reflexes in knee and ankles

• Gait issues

• Complete paralysis of the leg

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treatment for cauda equina syndrome

• Surgery to remove compressing factor

Corticosteroids

what is nociceptive pain

Caused by tissue damage.

what is neuropathic pain

Results from nerve damage.

what is functional pain

Caused by no obvious injury or damage to the body.

what is the steps of acute pain

• Transduction

• Transmission

• Perception

Modulation

what is transduction of pain

• Tissue damage results in release of inflammatory mediators

• These bind to nociceptors converting a thermal, mechanical or chemical insult into an electrical signal

transmission of pain

• Spinothalamic tract

• Spinoreticular tract

• Spinomesencephalic tract

perception of pain

• Nociceptive traffic is filtered through the individuals genetics, cognition, affect, environment, and previous pain experiences

differences in perception which may alter pain

• Context: beliefs, expectations, motivation

• Affect: depression, anxiety, emotional context

• Individual differences: genetics, gender

• Cognition: attention (distraction, hypervigiliance), suggestion

modulation of pain

• Cortical/subcortical impulses

• Impulses to the periaqueductal matter

• Locus coerulus (noradrenergic inhibitory system)

• Raphe nucleus (serotonergic inhibitory system)

• Inhibitor synapses in the dorsal horn

• Ascending spinothalamic tract

• Motor neuron reflex

Principles of acute pain management

• Enhanced recovery

• Management of expectations

• Multimodal analgesia

• Opioid sparing

Multimodal approach to acute pain management

• Multi-modal analgesia compared to opioid-based analgesia improve pain control and reduce opioid consumption and adverse effects thereby enhancing recovery

• Combination of medications with different modes or site of action

Predictors of pain and disability

Resilience model

• Acceptance

• Mindfulness

• Readiness for change

• Optimism

• Active coping

• Self-efficacy

Vulnerability model

• Anxiety

• Depression

• Fear of pain/re-injury

• Catastrophising

• Misattributions

• Somatic attention

what are Pain management programmes

• A psychologically based rehabilitation programme delivered in a group setting by an interdisciplinary team, the core members of which are a Clinical Psychologist, a Physiotherapist and a Medical Practitioner

• Aims to reduce the disability and distress caused by chronic pain by teaching sufferers physical, psychological and practical techniques to improve quality of life

function of peripheral nociceptors in pain processing

Specialized receptors that detect noxious stimuli and convert them into electrical signals

function of spinal cord in pain processing

Acts as a relay station, transmitting pain signals from peripheral nerves to the brain. It also plays a role in pain modulation through descending inhibitory pathways

function of thalamus in pain processing

Acts as a relay centre, transmitting pain signals to various parts of the brain.

function of limbic system and prefrontal cortex in pain processing

○ Limbic System: Involved in the emotional and affective aspects of pain.

Prefrontal Cortex: Involved in the cognitive and evaluative aspects of pain.

A variety of factors are released upon tissue damage which leads to the activation of nociceptors. These include

• Arachidonic acid

• Potassium

• 5-HT

• Histamine

• Bradykinin

• Lactic acid

• ATP

what are nociceptors

• Unencapsulated cutaneous receptors

• Larger the density of nociceptors, the greater the acuity in detecting stimuli

Different types of nociceptors exist:

• Mechanical nociceptors – detect the distension of skin (stretch) and pressure which elicit sharp, pricking pain.

• Chemical nociceptors – detect exogenous and endogenous chemical agents, such as prostanoids, histamines etc.

• Thermal and mechano-thermal nociceptors – detect thermal sensations that elicit slow and burning, or cold and sharp in nature, pain.

• Polymodal nociceptors – detect mechanical, thermal, and chemical stimuli.

function of Aδ fibres in pain processing

• All nociceptors except polymodal transmit to the dorsal horn of the spinal cord predominantly via Aδ fibres (myelinated fibres have a low threshold for firing and a fast conduction speed)

• Aδ fibres permit the localisation of pain and form the afferent pathway for the reflexes elicited by pain

• Terminate in Rexed laminae I where they mainly release the neurotransmitter, glutamate

where do Aδ fibres end

rexed laminae I

which neurotransmitter do Aδ fibres release

glutamate

function of C fibres in pain processing

• Polymodal nociceptors transmit to dorsal horn via C fibres

• Unmyelinated and a slow conduction speed

• Responsible for the secondary pain we feel which is often dull, deep, and throbbing in nature

• Large receptive fields and therefore lead to poor localisation of pain

• Terminate in Rexed laminae II (known as substantia gelatinosa) and release the neurotransmitter substance P

where do C fibres end

substantia gelatinosa (Rexed laminae II)

which neurotransmitter do C fibres release

substance P

which receptors does glutamate bind to and what does this cause

Glutamate binds to NMDA receptors to open calcium channels and allow calcium to enter the cell

Glutamate binds to AMPA receptors to open sodium channels and allow sodium to enter the cell

which receptor does substance P bind to and what does this cause

Substance P binds to NK-1 receptors which stimulate protein kinase C to remove magnesium blocked NMDA receptors

which receptor does CGRP bind to and what does this cause

CGRP binds to CGRP-R causing changes in neuronal excitability to cause sensitisation

Other neurotransmitters are released by primary afferent neurons terminating within the spinal cord such as

aspartate and vasoactive peptide.

what is hyperalgesia

• Enhanced sensation of pain at normal threshold stimulation

• An example of peripheral sensitisation is a release of substance P by the free nerve endings which stimulates surrounding cells to release molecules, potentiating pain

• An example of central sensitisation is an increase in the number of NMDA receptors, as well as increased sensitivity of NMDA receptors to glutamate

what is allodynia

• Sensation of pain experienced in response to a stimulus that was previously not painful

Three types of opioid receptors

• Mu

• Kappa

Delta

what are opioid receptors

Opioid receptors are inhibitory G protein-coupled receptors and their activation leads to a reduction in neurotransmitter release and cell hyperpolarisation, reducing cell excitability

There are three types of endogenous opioids:

• Β-endorphins – which predominately binds to mu opioid receptors

• Dynorphins – which predominately bind to kappa opioid receptors

Enkephalins – which predominately bind to delta opioid receptors

which endogenous opioid binds to Mu opioid receptors

B-endorphin

which endogenous opioid binds to kappa opioid receptors

dynorphins

which endogenous opioid binds to delta opioid receptors

enkephalins

which receptor is targeted in opioid therapy

Mu1 receptors

types of Mu opioid receptors

• μ1 = analgesia, physical dependence (this is an unwanted effect, where chronic use of the opioid produces tolerance. The negative physical withdrawal symptoms result from the abrupt discontinuation or dosage reduction).

• μ2 = respiratory depression, miosis (constriction of pupil), euphoria, reduced GI mobility, physical dependence.

• μ3 = possible vasodilation.

types of delta opioid receptors

δ1 and δ2 = analgesia, antidepressant effects, convulsant effects, physical dependence.

types of Kappa opioid receptors

κ1, κ2, κ3 = analgesia, anticonvulsant effects, depression, hallucinogenic effects, diuresis, dysphoria, sedation, stress.

How do endogenous opioids reduce transmission in spinal cord

• Within the spinal cord, both dynorphins and enkephalins can act to reduce the transmission of pain signals in the dorsal horn.

• This is because the post-synaptic ends of second-order neurones have opioid receptors within the membrane.

How do endogenous opioids reduce pain

nhibition of adenylyl cyclase – opioids reduce the intracellular cAMP content. This affects protein phosphorylation pathways and hence cell function.

• Opiates promote the opening of potassium channels – this reduces synaptic transmission as it causes the axon membrane to be in a state of hyperpolarisation.

• Inhibit the opening of calcium channels – this reduces the amount of neurotransmitter released into the synaptic cleft, thus reducing synaptic transmission.

World Health Organisation (WHO) Analgesic Ladder

• Step 1 (mild to moderate pain) – Non-opioid (paracetamol, aspirin or NSAID) +/- an adjuvant (low dose tricyclic antidepressant/ anticonvulsant/ muscle relaxant/ other NSAIDs)

• Step 2 (moderate to severe pain) – Weak opioid (codeine/ tramadol) +/- a non-opioid +/- an adjuvant

• Step 3 (Severe pain) – Strong opioid (morphine/ fentanyl/ diamorphine) +/- a non-opioid +/- an adjuvant

types of Mechanical sensitive receptors

• P2X (ionotropic purinoceptor)

• P2Y (G-protein-coupled pyrimidinergic receptor)

• TRPA1

• TRP (transient receptor potential channel)

types of H+ sensitive receptors

• TRPV1

• ASIC (amiloride-sensitive cation channel)

types of thermal sensitive receptors

• Cold- TRPM8

Heat- TRPV1

Types of neuropathic pain

a. Traumatic (nerve entrapment or injury)

b. Central (stroke, spinal cord injury)

c. Neurotoxic (microtubule-stabilising agent- induced neuropathy)

d. Infectious (HIV-neuropathy and post-herpetic neuralgia)

e. Metabolic (diabetic neuropathy and alcohol-induced neuropathy)

Idiopathic

What is sensitisation

• Increased responsiveness of nociceptors to their normal input, and recruitment of a response to usually subthreshold inputs

• Included drop in threshold or increase in suprathreshold response

• Spontaneous discharges and increases in receptive field size may occur

what is nociplastic pain

pain that arises from altered nociception despite no evidence of actual or threatened tissue damage

• Examples include fibromyalgia, complex regional pain syndrome, musculoskeletal pain

Mechanisms of neuropathic pain

1. Increased inflammation

2. Altered nociceptive activity (receptor/ion channel expression) inducing peripheral sensitisation

3. Altered spinal processing, central sensitisations, synaptic reorganisation

Altered central processing, descending inhibition

Treating neuropathic pain

Acute- paracetamol, NSAIDS, opioids

Chronic- antidepressants, anti-convulsant, opioids

Factors affecting pain experience

• Context: beliefs, expectations, motivation

• Affect: depression, anxiety, emotional context

• Individual differences: genetics, gender

• Cognition: attention (distraction, hypervigilance), suggestion

Common chronic pain conditions

• Fibromyalgia

• Lower back pain

• Arthritis

• Migraines

• Neuropathic pain

• Complex regional pain syndrome (CRPS)

Temporomandibular joint disorders

Non-pharmacological management of pain

• Heat

• Ice

• Massage therapy

• Physical therapy

• Transcutaneous electrical nerve stimulation (TENS) unit

• Spinal cord stimulator

Acupuncture and relaxation techniques

what is Transcutaneous electrical nerve stimulation

• Portable, pocket-sized, battery powered device that attaches to your skin and uses mild, safe electrical signals to help control pain

what is Spinal cord stimulator

• Electrode implanted near spinal cord

• Sends mild, safe electrical signals to relax nerves causing pain

MOA of NSAIDs

reversibly inhibit COX enzymes

The degree of selectivity for COX-1 relative to COX-2 can be used to classify NSAIDs as:

• Nonselective NSAIDs (includes most NSAIDs, such as diclofenac, ibuprofen, indomethacin, and naproxen). These act on both COX-1 and COX-2 enzymes.

• Coxibs (for example celecoxib and etoricoxib). These are highly selective for COX-2 enzymes but can interact with COX-1 in certain circumstances.

side effects of NSAIDs

• Stomach pain

• Nausea

• Bleeding

• Ulcers

• gas

name strong opioids

• Morphine

• Meperidine

Fentanyl

name moderate opioids

• Codeine

Oxycodone

name weak opioids

Propoxyphene

Side effects of opioids

• Nausea- activation of chemoreceptor trigger one in medulla

• Respiratory depression- reduce brainstem responsiveness to co2 and affect respiratory centres in pons

• Suppression of immune system

• Drowsiness

Addiction

MOA of paracetamol

• Thought to inhibit COX enzymes within CNS

• Analgesic and antipyretic properties

No effect on inflammation

side effects of paracetamol

• Nausea

• Vomiting

• Constipation

• Abdominal pain

Rashes and itching

MOA of TCAs

block the reuptake of amines by nerve terminals, by competition for the binding site of the amine transporter

MOA of GABApentin

Gabapentin increases the synaptic concentration of GABA, enhances GABA responses at non-synaptic sites in neuronal tissues, and reduces the release of mono-amine neurotransmitters (catecholamines

side effects of GABApentin

GI disturbance, addiciton

Aims of the Psychology input to the programme:

• Help patients move from a medical model of pain to a biopsychosocial model of pain and disability.

• Build patients’ self-management skills and reduce reliance on healthcare professionals.

• Educate about the physiological effects of pain.

• Address psychological, social and emotional barriers to progress.

• Facilitate positive lifestyle changes.

• Improve mood / reduce emotional distress.