Untitled Flashcards Set

LESSON 2: PATHWAYS OF PAIN AND MECHANISMS

1ST SEMESTER - MIDTERMS | DR. MANOLETTE GUERRERO

PAIN

● Nature's earliest sign of morbidity

● Most common symptom of disease

● Patient is suffering

● An unpleasant sensory emotional experience associated with actual

or potential tissue damage or described in terms of such damage

● Both a “sensation” and “emotion”

PAIN TRANSMISSION

● Should have an intact spinothalamic system

● Pain stimuli has to go from receptors to cortex through the pain

pathways

● We consciously feel pain when it reaches the cortex

SUBSTANSIA GELATINOSA

● The doorway of pain into the central nervous system

● Cell bodies in dorsal horn

● Gate that receives pain stimulus from receptors

● May be modulated from higher centers

○ The doorman, controls the Substantia Gelatinosa

SENSORY DISCRIMINATIVE ASPECT OF PAIN

● Subserved by the pain pathways to the sensory areas of the cortex

● Localization & Identification of pain

TRANSMITTERS OF PAIN

EXCITATORY NEUROTRANSMITTERS

● Excitatory neurotransmitters chemicals that carry pain stimulus from

neuron one to another

● Substance P

○ Excites nociceptive dorsal horns

● Calcium

● Enzymes:

○ Histamine

○ Prostaglandins

INHIBITORY

● Prevent pain transmission

● Serotonin

● GABA

● Opioid peptides: Inhibit at dorsal horn

○ Endorphins

○ Enkephalin

○ Dynorphin

PAIN PATHWAY AND INTERCONNECTIONS

● Receptors → substantia gelatinosa ( in the dorsal horn of the spinal

cord) → decussate in the spinal cord → lateral/ anterior white matter

→ tegmentum → brain stem → VPL of Thalamus → Cortex ( area 3, 1,

2)

○ for the localization and identification of pain

● Spinoreticular pathway

○ emotional pathway of pain

○ Brain stem → reticular formation → Hypothalamus (limbic

lobe) → amygdala

● Periaqueductal Gray

○ Modulated the substantia gelatinosa

○ Since it is in the limbic lobe it is influenced by emotion

ASCENDING PAIN PATHWAYS CONTRIBUTE TO THE RETICULAR FORMATION

● Reticular Formation connects to hypothalamus

○ Pain enters the substantia gelatinosa → decussate at spinal

cord → level of brain stem → Reticular formation →

structures of limbic lobe (hypothalamus , amygdala) →

periaqueductal grey (has fibers that modulate the substantia

gelatinosa)

● Hypothalamus connects to the Amygdala

PAIN ACTIVATES THE RAS

● Inputs from the ascending pain pathway to the Reticular Formation

● Activate the RAS resulting in alertness

○ Wake you up from sleep

○ Pain will not make you sleep

CENTRAL MODULATION OF PAIN RECEPTION

● Acts on the dorsal horn of the spinal cord

● Has contribution from amygdala

● Modulates pain input at substantia gelatinosa

○ Emotions could : enhance or inhibit pain

AFFECTIVE MOTIVATIONAL ASPECT OF PAIN

● Subserved by diffuse projections of pain fibers to the limbic & frontal

lobes

○ Affects how much you perceive pain

● Unpleasant feelings of pain

Noxious stimulus → peripheral nerve → dorsal root ganglion→ Substantia

Gelatinosa → neurotransmitter (Substance P) → spinal cord (decussate) →

VPL of Thalamus –. Area 3,1,2 = sensory discriminative aspect of pain

Substantia Gelatinosa → neurotransmitter (Substance P) → spinal cord

(decussate) → spinoreticular tract → Reticular Formation → Limbic lobe

EFFECTS OF OPIODS

Periaqueductal Grey

● Modulate Substantia Gelatinosa

● Inhibitory neurotransmitters e.g endogenous opioids

○ Inhibit substance P.

CLASSIFICATION OF PAIN BY PATHOPHYSIOLOGY

● Nociceptive pain

○ Somatic

○ visceral

● Neuropathic pain

○ Peripheral

○ Central

TYPES OF PAIN

● Nociceptive

○ Ischaemic

■ Lack of blood flow

○ Inflammatory

■ infections

○ Traumatic

○ Metabolic

■ Different substances (eg. uric acid )

○ Toxic

● Neuropathic

● Idiopathic

○ Mixed pain

NEUROPATHIC PAIN

● Primary lesion or dysfunction of the PNS or CNS that leads to either

excess stimulation of the pain pathways or damage to the

non-nociceptive sensory pathways, which alter the balance between

painful and non painful inputs to the CNS

IASP DEFINITIONS

● Neuropathic Pain

○ Pain initiated of caused by a primary lesion or dysfunction in

the nervous system

● Peripheral Neuropathic Pain

○ Pain initiated or cause by a primary lesion or dysfunction in

the peripheral nervous system

● Central Neuropathic Pain

○ Pain initiated or caused by a primary lesion or dysfunction in

the central nervous system

NOCICEPTIVE NEUROPATHIC

● Pain that arises from a

stimulus that is outside of

the nervous system

● Proportionate to the

nociceptive stimulation

of the receptor

● When acute serves a

protective function

● Pain initiated or caused by a

primary lesion or

dysfunction in the nervous

system

● No nociceptive stimulation

required

● Disproportionate to the

stimulation of receptor

IT’S THE GOAT

● Other evidence of nerve

damage

TYPES OF NEUROPATHIC PAIN SYNDROME

LESION IN THE PNS

● POST HERPETIC NEURALGIA

● DIABETIC NEUROPATHY

● COMPLEX REGIONAL PAIN SYNDROMES

● PHANTOM LIMB PAIN

● TRIGEMINAL NEURALGIA

● LOW BACK PAIN SYNDROME WITH SCIATICA/ HERNIATED

DISCS

○ Mixed pain syndrome

● CERVICAL HERNIATED DISCS

○ Mixed pain syndrome

● CARPAL TUNNEL SYNDROME

NEUROPATHIC PAIN SYNDROME IN THE CNS

● Central neurogenic pain:

● Central / thalamic pain post-stroke

■ If VPL is affected it can enhance pain

● Myelopathic pain due to multiple sclerosis or post-traumatic

injury

DESCRIPTION OF NEUROPATHIC PAIN

● burning , shooting

● Stabbing

● Paroxysmal

● Vice-like

● Paresthesia

● Associated sensory impairment

● Allodynia, hyperalgesia, hyperpathia

● Altered sympathetic function

● CPRS

● Immediate or delayed onset

● Intensity altered by fatigue or emotion

OTHER CLINICAL FEATURES ASSOCIATED WITH NEUROPATHIC PAIN

● Insomnia

○ Due to activation of RAS

● Anxiety

● Depression

● Weight loss

● Decreased quality of life

SPONTANEOUS SYMPTOMS OF NEUROPATHIC PAIN

Spontaneous pain Burning, shock-like

Dysesthesia Abnormal, unpleasant sensations

(eg, shooting, lancinating, burning)

Paresthesia Abnormal, not unpleasant

sensations (eg, tingling)

STIMULUS EVOKED SYMPTOMS NEUROPATHIC PAIN

Allodynia Painful response to a non- painful

stimuli

Hyperalgesia Heightened response to a painful

stimulus

Hyperpathia Delayed, Explosive pain to a

stimulus

TERMS USED TO DESCRIBE PAIN

● Hyperalgesia: Increased sensitivity & a lowering of the threshold to

pain stimuli ( inflammation, skin burns)

● Hyperpathia: excessive reaction to pain

● Hypoalgesia: decreased sensitivity & a raised threshold to painful

stimuli

● Allodynia: defect in pain perception-increased sensitivity to all

stimuli even those that do not normally evoke pain

3 GENERAL MECHANISMS OF NEUROPATHIC PAIN

1. Ectopic Focus

a. Damage in Central or Peripheral nervous system ; fire painful

stimuli without noxious stimuli

2. Peripheral & Central Sensitization

3. Loss of Local & Central Inhibition

Note: These three mechanisms are reasons why there is excessive pain

transmission thru pain pathways

ECTOPIC FOCUS

LOSS OF LOCAL & CENTRAL INHIBITION

● Disinhibition in which nerve injury reduces inhibition in dorsal horn

through various mechanisms

● Excitability in dorsal horn neurons is determined by balance between

excitatory inputs from primary afferents and inhibitory inputs (local

and descending)

○ Periaqueductal grey ( central inhibition)

○ Spinal cord (local)

● Nerve injury reduces inhibitory input, increasing excitability in dorsal

horn neurons. Primary afferent inputs now evoke a much greater

response, and dorsal horn neurons may fire spontaneously

PERIPHERAL SENSITIZATION

● Spontaneous activity in primary afferents can produce peripheral

sensitisation in injured and uninjured adjacent neurons. Partial

denervation increases relative concentrations of neuron growth

factor for intact cells

○ Threshold is lower

○ Becomes more sensitive

CENTRAL SENSITIZATION

● Increased nociceptor drive leads to central sensitization of dorsal

horn neurons. Ab fibre input is now sufficient to activate spinal cord

pain pathways

○ After nerve injury, increased input to the dorsal horn can

induce central sensitization

Note:

● if substantia gelatinosa or thalamus is sensitive then a little stimuli is

felt as great pain

● Greatly affected by emotions

Central sensitization: Underlying cause of amplified pain perception

associated with PDN

● Central sensitization is believed to be the underlying cause of

amplified pain perception that results from dysfunction in the CNS

1,2

● This is believed to result from excessive release of two important

neurotransmitters, substance P and glutamate

Insert photos

TYPES OF PAIN SEEN IN PRACTICE

● Nociceptive

○ Tissue damage, musculoskeletal, headaches, spasticity

contractures

● Mixed Nociceptive and Neuropathic

○ Cervical & Lumbar spine disease

● Neuropathic

○ CNS or PNS damage

● Dysfunctional Neurological Pain

○ Complex regional pain

AREAS OF DAMAGE FOR NEUROPATHIC PAIN

● Peripheral Nerve (neuropathies)

● Radiculopathies ( Spinal Roots)

● Myelopathies

● Brainstem Lesions

IT’S THE GOAT

● Thalamic Lesions

● Cortical / Subcortical

TYPES OF NEUROPATHIC PAIN SYNDROMES

● Post Herpetic Neuralgia

● Diabetic Neuropathy

● Complex Regional Pain Syndromes

● Phantom Limb Pain

● Trigeminal Neuralgia

CLINICAL FEATURES OF DIABETIC NEUROPATHY : DISTRIBUTION OF PAIN

● Feet and ankles: “glove and stocking” (most common)

● Lower extremities above the knees

● Upper extremities (least common)

PAIN IN ACUTE PHASE OF HERPES ZOSTER

● Sharp burning pain in the involved dermatome

● May precede lesions

● Inadequate relief may lead to post herpetic neuralgia cSHARP

COMPLEX REGIONAL PAIN SYNDROMES: A VARIETY OF PAINFUL

CONDITIONS THAT USUALLY

● Follow injury

● Occur regionally

● Have distal predominance of abnormal findings

● Exceeds in both magnitude & duration the expected clinical course of

the inciting event

● Often result in significant impairment of motor function

● Show variable progression over time

COMPLEX REGIONAL PAIN SYNDROMES

● Reflex sympathetic dystrophy

● Causalgia

● Shoulder hand syndrome

● Acute bone atrophy

● Post traumatic painful osteoporosis

CLINICAL FEATURES OF CRPS

● Inflammatory :

○ pain, color, change temperature, change limited ROM, worse

with exercise, edema

● Neurological :

○ Hyperpathia, Hyperaesthesia, Tremor, Paresis,

Incoordination

● Dystrophic:

○ skin, nails, muscle, bone

● Sympathetic :

○ hyperhidrosis, changes hair growth and nail growth

TREATMENT OF NEUROPATHIC PAIN

● Local

○ Physical: TENS, Acupuncture , heat , cold

○ Pharmacological: local anaesthesia, Capsaicin

● Blocks

○ Peripheral nerve , roots, plexus ; sympathetic ganglia,

sympathectomy

● Stimulation

○ Tens, Spinal Cord Stimulation, Deep brain stimulation

● Systemic Drugs

○ Anticonvulsant, antidepressant , opioids

● Psychological Interventions

○ Behavioral Therapy, Emotion Response to pain

● Rehabilitation

LEARNED PAIN

THE BRAIN ALWAYS CONTROLS THE PAIN SIGNALS WE FEEL

● Pain Matrix: pain responsive regions :these areas are far more plastic

depending on the stimulus they receive

○ Thalamus

○ Somatosensory Cortex

○ Insula

○ Anterior Cingulate Cortex

We always correlate pain with a body part

● Pain is always projected with a body part

● Body image is created in a brain map

● Some people can have a wrong perspective of their body

Placebo Effect = Context Effect

● Sight

● Smell

● Words

● Touch

Knowing one is taking a pain drug reduce pain

● Nocebo suggestion: make feel more pain

● Placebo suggestion : pain will get better