Neuropathic, Nociplastic & Mixed Pain

Neuropathic Pain

Pain caused by lesion or disease of somatosensory NS

1. Central neuropathic

2. Peripheral

Peripheral NS Branching Logic

Somatic NS: sense organs and voluntary mm

• Sensory NS (afferent): inputs

• Motor MS (efferent): output

Autonomic → Sympathetic (arouse) and parasympathetic (calm)

Neuropathic Pain Diagnoses Classifications + E.g.

Peripheral: trigeminal, peripheral nerve damage, polyneuropathy, post herpetic neuralgia, radiculopathy

• Amputations, surgery, trauma, diabetic polyneuropathy, chemo induced

Central: brain injury pain, central post-stroke pain, pain w/ MS, pain w/ SC injury

• Traumatic, birth injury, tumor

Neuropathic pain prevalance

• Higher in diabetic populations

• More so in females

• And ppl > 50 yrs old

Neuropathic pain in #1 transduction

Spontaneous activity/pain in primary afferents

From nociceptive neurons

i.e. Electric shock out of the blue

Neuropathic pain in #2 transduction/transmission

Excitatory signals ascending from periphery, SC, brain due to structural changes

• Ion channel fxn

• Larger receptor fields

• 1+2 order MN

• Fxnl changes (Sensitization)

Neuropathic pain in MODULATION

IMPAIRED DESCENDING INHIBITION

• Why opioids are ineffective

Peripheral Sensitization

More responsive and lower threshold of nociceptive neurons in periphery to stimulation of their receptive fields

• More TRANSDUCTION of nociceptive signals from periphery to SC

• Non-noxious causes pain

Central sensitization

More responsive nociceptive neurons in CNS compared to norm/sub-threshold afferent input.

• More TRANSMISSION of signals from SC - brain

• AP fire for longer = pain longer

Location of pain means….

Corresponds to location of innervation by injured structure

Postherpetic neuralgia pain location (peripheral)

Unilateral in 1+ spinal dermatome or trigeminal nerve territory

Peripheral nerve injury pain location

Follows peripheral nerve map distribution

Distal to trauma site

Painful polyneuropathy pain location (peripheral)

Feet, lower leg, thighs, hands

Painful radiculopathy pain location (peripheral)

Follows dermatome map (innervation of nerve root)

Neuropathic pain from SCI (central) location

@ or below spinal cord lesion

Central post stroke pain location

Affected limbs are OPPOSITE to stroke

Lateral medullary infarction: opposite limbs affected, facial pain distribution is ipsilateral

Central neuropathic pain from MS location

All over body

Combined distribution

Pain Quality Scale for neuropathic pain

PROMIS measure of neuropathic pain

Paresthesia

Abnormal sensation

Spontaneous or evoked

Dyesthesia

Unpleasant abnormal sensation

Spontaneous or evoked

Hyperesthesia

More sensitive to stimulation, excluding special senses

Hypoesthesia

Less sensitive to stimulation, excluding special senses

Hyperalgesia

More pain from noxious stimuli

Hypoalgesia

Less pain to noxious stimulus

Anesthesia

No sensation in response to a stimulus

Neuropathic pain considerations in practise

Touch aggravates pain (i.e. clothes, exam)

Stimulanenous numb or sensory gain

Sensory changes occur w/ other pain mechanisms

• Location of sensory changes

Paradoxical pain

Numb and sensitive

Coexist

Temporal Features

Ectopic activity of nociceptors

Spontaneous pain.

Onset of pain not correlate w/ onset of nerve injury/disease.

• Can be delayed; not happen at same time as injury.

Pain intensity

Doesn’t always correspond w/ degree of neuro damage

First line pain relief for neuropathic pain

Not always work

Treatment for neuropathic pain

Manage symptoms not underlying disease

Treat underlying disease not correlated w/ improvements in pain

Require specialists and unique interventions

• Graded motor imagery

• Mirror therapy

• Sensory retraining

Nociplastic pain

• Error in detecting danger + pain processing

• Modulation impaired

• Increased feedback loop. Altered nociception.

• CNS is hyper excitable

• Immune system release of cytokines - bad feelers

• Affects CNS, brain, immune system

Pain w/o tissue damage

Pain from altered nociception w/o tissue damage

Examples of Nocicplastic pain

Chronic primary pain

• Headache disorders

• IBS

• Non specific LBP

Cause of Nocicplastic pain

Unknown

Dysfxn of NS of peripheral and central NS

Structural + fxnl changes of nociceptive neurons

• On a spectrum

Field is grey

Nocicplastic Physiological Changes in the periphery

Larger receptor fields in periphery

Peripheral sensitization (more responsive, lower threshold)

More inflammatory mediators - localized inflammation

Nociplastic changes in Spinal cord to 2nd order NN

Structural: larger receptor fields

Function: central sensitization (more responsive, lower threshold)

Spontaneous activity

Nociplastic changes in brain to 3rd order NN

Functional changes: central sensitization

Functional changes in modulation: lose descending inhibition. Increased descending facilitation [dampen pain response to everyday things]

Structural changes: organization of cortex. pain areas enlarged

Temporal Summation/wind up

Successive increase in AP due to rapid, repeated stimulation

Overall increased pain perception

Last pin prick rlly hurts bc more signals sent to brain

Wind up in SC: enhanced response of nociceptors (more nociceptive signals transmitted w/ repeated transduction)

Pain location in nociplastic pain

Widespread

No correlation w/ anatomical structures

Nociplastic pain co-morbid symptoms

Sensitivity to other sensations

i.e. lights, sounds, temp

All sensations heightened

Co-exist or a result of diff nociplastic pain

Provoking factors in nociplastic pain

Due to CS, many stimuli provoke pain (also non-noxious)

Quality in nociplastic pain

Many descriptors

Widespread non specific

Severity in nociplastic pain

High intensity ratings

Not correlated w/ tissue damage

Temporal in nociplastic pain

Pain @ rest

Evoked or spontaneous by move or touch

Treatment for nociplastic pain

Focus on NS bc pain itself is the disease

• NOT tissues (pain not associated w/ tissue damage)

Educate, active/exercise based strategies, self management

Sensitization based off mechanisms

Inflammatory pain: PS > due to inflammatory mediators

• Short term

Neuropathic pain > PS + CS > due to nerve damage

Nociplastic pain > PS + CS

• Long term lasting changes

Mixed pain definition

Pain starts as nociceptive/neuropathic → nociplastic over time

• i.e. arthritis → nociplastic changes

OR

Pain w/ multiple pain mechanisms [combo] that co-occur

• i.e. surgery > nociceptive from cut + neuropathic + inflammatory pain

• i.e. sciatica, cancer, OA post surgical

Pain @ MANY body sites that each have distinct mechanisms contributing to persons overall pain experience

• i.e. Person w/ TMJ, IBS, acute ankle sprain

For pain conditions that don’t fit

Mixed pain physiology

Co occur w/ existing mechanisms

OR

Unique mechanism

OA Pain

Mixed pain: signs of sensitization

• Initially thought as Nociceptive

Evidence of low grad inflammation contributing to inflammatory pain

• changed innervation of joint - neuroapthic pain

Increased innervation of osteochondral junction + cartilage (poorly innervated), loss of synovial lining