Case 1: Henry Baker - Chronic Pain

Hurt

Pain experience + intensity

Harm

Tissue damage + injury

Nociceptors

Primary sensory cells with free nerve endings

React to harmful stimuli = Pain

• Proportional sensors = No adaptation to chronic constant pain

Nocicpetors: Classification

Mechanical

Thermal

Polymodal

Mechanical Nociceptors

React to mechanical stimuli

Thermal Nociceptors

React to thermal stimuli

• > 45ºC

• < 5ºC

Polymodal Nociceptors

React to thermal, mechanical, + chemical stimuli

Pain Nerve Fibres

Aδ fibre

C fibre

Aβ fibre

Aδ Nerve Fibres

Myelination: Yes

Conduction Speed: Fast

Nociceptor: Mechanical, thermal

Localizability: Localized

Sensation:

• Sharp

• Pricking

• Stinging

Function: Withdrawal response

C Nerve Fibres

Myelination: No

Conduction Speed: Slow

Nociceptor: Polymodal

Localizability: Diffuse

Sensation:

• Dull

• Aching

• Burning

Function: Protect injured area (guarding)

Aβ Nerve Fibres

Transmit non-noxious (tactile) + nociceptive signals

Modulate Aδ + C fibre activity

Pain: Excitatory Neurotransmitters

Receptors: Nociceptors + AMPA

Glutamate

Pain: Inhibitory Neurotransmitters

Receptors: Interneurons + NMDA (closed at rest)

GABA

Glycine

Opioids: Endorphins (endogenous)

Pain Pathway 1

Nociceptors detect noxious stimuli = Convert into electric signal/action potential = C + Aδ fibres depolarize + transmit afferent information to dorsal horn (spinal cord)

• Gate-Control Theory: Excitatory nociceptors increase afferent transmission

  • Increase excitatory signals + decrease interneuron firing = Open gate = Increase pain transmission

1st Order Neuron:

• Cell Body:

  • Spinal ganglion

  • Trigeminal ganglion

• Synapse:

  • Dorsal horn (spinal cord)

  • Spinal trigeminal nucleus (brainstem)

Pain Pathway 2

Transmit afferent input up spinothalamic (anterolateral) tract to thalamus

Decussate in spinal cord/brainstem = Ascend contralaterally

• Gate-Control Theory: Inhibitory interneurons control afferent transmission

  • Aβ fibre activation = Increase interneuron firing = Close gate = Decrease pain transmission

2nd Order Neuron:

• Cell Body:

  • Dorsal horn

  • Spinal trigeminal nucleus

• Synapse: Thalamus

Pain Pathway 3

Brain perceives pain

• Somatosensory cortex = Conscious pain perception

• Limbic system = Emotional pain perception

3rd Order Neuron:

• Cell Body: Thalamus (ventral posterolateral nucleus)

• Synapse: Somatosensory cortex + limbic system

Pain Pathway 4

Brain sends response down efferent pathways = Pain modulation/reaction

Chronic Pain: Description

Distressing sensory + emotional experience linked/resembling tissue injury

Duration:

• Acute: < 1 month

• Subacute: 1-3 months

• Chronic: > 3 months

Chronic Pain: Types

Nociceptive

Neuropathic

Nociplastic

Chronic Pain: Nociceptive

Triggered by noxious stimuli

Somatic (MSK): Localized + sharp pain

• Aδ fibres

Visceral: Diffuse + dull/deep pain

• C fibres

Chronic Pain: Neuropathic

Triggered by damage to/dysfunction of somatosensory nervous system (no noxious stimuli)

Central: CNS dysfunction

• Poststroke pain syndrome

• Phantom limb pain syndrome

Peripheral: Peripheral nerve damage

• Diabetic neuropathy

• Postherpetic neuralgia

Chronic Pain: Nociplastic

Triggered by altered nociception

No underlying tissue damage

Chronic Pain: Epidemiology

Risk factors…

• Older age

• Smoking

• High ACEs

  • Foster care

  • Parental death in childhood

• Premature birth

• Physical trauma at young age

Chronic Pain: Social Burden

Increased productivity loss

• Disability

• Missing work

• Caregiving responsibilities

• Decreased societal participation

Chronic Pain: Economic Burden

Healthcare costs

• Leading cause for seeking medical care

• Cause disability

Chronic Pain: Etiology

Biopsychosocial model = Modulate pain intensity + impact

Biological:

• Tissue injury

• Genetics

Psychological:

• Pain-related beliefs

  • Fear-Avoidance Model: Worry about activity worsening pain = Avoiding activity = Worsens pain from lack of use

• Coping mechanisms

• Catastrophizing

Social:

• Social support system

• Work

Chronic Nociceptive Pain: Pathophysiology

Nociceptors detect pain = Transmit up spinothalamic tract to brain = Somatosensory cortex + limbic system perceive + response to pain

Chronic Neuropathic Pain: Pathophysiology

Abnormal nerve impulse transmission

Peripheral: After trauma, disease, neurotoxins

Central: After stroke, spinal cord injury, demyelinating condition

Chronic Pain: Pain Signalling Evolution

1. Persistent injury = Nociceptor changes = Decrease nerve/firing threshold

• Enhanced excitatory transmission: Increase nociceptor firing

  • Peripheral Sensitization: Decreased activation threshold = Weak stimuli trigger neuron firing = Spontaneous firing

  • Central Sensitization: Repeat noxious stimuli = Signalling pathway + Glutamate receptor changes = Normal stimuli causes pain (allodynia)

  • Wind-Up: Normally inactive receptors activate = Ca2+ influx = Increase neuron firing frequency + amplitude

• Disinhibition: Decrease interneuron inhibiting nociceptor firing

2. Autonomous firing = Pain persists after insult resolution

Chronic Pain: Clinical Presentation

Primary: No clear underlying condition OR pain disproportionate to cause

• Distress

• Disability

• Ex:

  • Fibromyalgia

  • Chronic regional pain syndrome

  • Abdo pain

  • MSK pain syndromes

Secondary: From disease

• Ex:

  • Cancer

  • Nerve injury

  • RA

Chronic Pain: Yellow Flags

Fear-avoidance beliefs

Catastrophizing

Depression + anxiety

Exaggerated illness response

Prolonged sick leave

Lack of social support

Overprotective family

Chronic Pain: Investigations

Cannot use disease model approach

• Treating pain as symptom of disease

Indications:

• Red flags for disease

• Neurologic deficit

• Treatment failure

Blood tests

Imaging

Chronic Pain Investigation: Blood Tests

CBC

Inflammatory markers (ESR, CRP)

Immune markers (HLA B27)

BMP

Chronic Pain Investigation: Imaging

MRI

XR

Chronic Pain: Treatment/Management

Physical

Psychological

Pharmacological

Chronic Pain Management: Physical

PT/OT

Massage

Thermotherapy

Desensitization

Lifestyle changes

• Regular exercise

• Weight loss

Chronic Pain Management: Psychological

CBT

Hypnosis

Relaxation techniques

Chronic Pain Management: Pharmacological

WHO Analgesic Ladder

Step 1: Mild Pain

• Non-opioids

• Adjuvants if needed

Step 2: Moderate Pain

• Non-opioids

• Mild opioids (consider)

• Adjuvants if needed

Step 3: Severe Pain

• Non-opioids

• Mild opioids (consider)

• Strong opioids (consider)

• Adjuvants if needed

Chronic Pain Pharmacological: Regular Analgesics

Administer at fixed time + dose

By Mouth: Preferred

By Clock: Regular administration at fixed times

By Ladder: Pain persists = Step up

Chronic Pain Pharmacological: PRN Analgesics

Short-acting

≥ 3x/day = Review regular medication

Chronic Pain Pharmacological: Analgesic Drugs

Acetaminophen

NSAID

Selective COX-2 inhibitor

Na+ channel blocker

Opioids

Combination

Analgesic: Acetaminophen

Admin: Oral, suppository

Analgesic: NSAID

Aspirin, indomethicin

• Admin: Oral, suppository

Ibuprofen

• Admin: Oral, parenteral

Diclofenac

• Admin: Oral, parenteral, topical

Naproxen, Meloxicam

• Admin: Oral

Ketorolac

• Admin: Parenteral

Analgesic: Selective COX-2 Inhibitor

Celecoxib

• Admin: Oral

Analgesic: Na+ Channel Blocker

Suzetrigine

• Admin: Oral

Lidocaine

• Admin: Topical

Analgesic: Opioids

Oxycodone

• Admin: Oral

Hydromorphone, Tramadol

• Admin: Oral, parenteral

Morphine, Fentanyl, Buprenorphine

• Admin: Parenteral

Analgesic: Combination

Codeine/acetaminophen

Hydrocodone/acetaminophen

Hydrocodone/ibuprofen

Oxycodone/acetaminophen

Admin: Oral

Opioids: Indications

Canadian Opioid Guidelines (2025)

First-Line: Non-opioid + non-pharmacological therapies

Opioids: Trial if pain persists

• No psychiatric disorders

• No SUD

• No opioid OD history

Rotate opioids if pain persists or adverse effects

Opioids: Dosing

< 80mg daily

Opioids: Adverse Effects

Hyperalgesia (pain sensitization)

Respiratory depression

Constipation

Hypogonadism

Serotonin syndrome

Seizures

Withdrawal

Dependence

• Using others’ prescriptions

• Dose escalation

• Visiting multiple physicians/prescribers

• Early refill

• Impacted function

Adjuvant Pain Drugs

Anticonvulsants

Muscle relaxants

Antidepressants

Cannabinoids

Adjuvant Drugs: Anticonvulsants

Indications: Neuropathic pain

Ex:

• Gabapentin/pregabalin

• Carbamazepine

Adjuvant Drugs: Muscle Relaxants

Indications: Muscle spasticity

Ex: Baclofen

Adjuvant Drugs: Antidepressants

Indications:

• Chronic pain syndromes

• Neuropathic pain

TCAs:

• Amitriptyline

• Clomipramine

SNRIs:

• Duloxetine

• Venlafaxine

Adjuvant Drugs: Cannabinoids

Indications: Neuropathic pain (short-term)

• NOT INHALED

CBD: Non-psychoactive

THC: Psychoactive

• Binds CB1 + CB2 = Inhibit cAMP synthesis = Analgesia

Chronic Pain: Complications

Financial burden

Poor mental health

• Altered family dynamics

• Increased stress

• Depression

• Anxiety