Chronic and Neuropathic Pain

What are the four steps of pain processing

Transduction (pain stimuli) → Conduction/transmission (AP travel) → Modulation (signal adjustment) → Perception (experience of pain)

What is peripheral sensitization

Primary afferent nociceptors at injury site cause inflammation → Primary hyperalgesia = increased response to pain at injury site

What is central sensitization

CNS drives NMDAr activation, GABA inhibition → Secondary hyperalgesia = pain spread to uninjured areas

What happens with stimulation of non-NDMA glutamate receptors

Low freq: Activation of non-NDMA → Na influx and depolarization

High freq: Activate non-NDMA and NDMAr → NDMA opening → Ca influx

What is the action of nitric oxide in central sensitization

Ca enter NDMA → Protein kinase activation and NOS → NO is retrograde presynaptic terminal → Release glutamate and substance P

What are the causes of neuropathic pain

Mutation changes receptor/ion channel

Nerve/axons/myelin is damaged → Axonal/demyelinating neuropathy

Lesion of spinal cord, brain, brain stem, thalamus cause neuropathic pain

What are the symptoms of neuropathic pain

Continuous pain, paroxysmal pain, provoked pain

What are the criteria to grade neuropathic pain

Possible: based on history and neuroanatomy

Probable: confirmed sensory sign in same neuroanatomical distribution

Definite: Diagnostic test confirm lesion

What is nociplastic pain

Pain from altered nociception despite no clear evidence of actual/threatened tissue damage

What are the characteristics of nociplastic pain

Last longer than 3 mo; pain is widespread, regional or multifactorial; hyperalgesia and allodynia; comorbidities like brain fog, mood change, fatigue, unrefreshing sleep

What regions are related to nociplastic pain

Default mode network (DMN), salience network (SLN) and sensorimotor network (SMN) → Increased connectivity

Descending pain modulatory system (DPMS) → Modulate spinal dorsal horn activity

What is characteristic of top down nociplastic pain

Female »» Male, Young onset (puberty), family history of pain, high psychological comorbidity, allodynia, pain does NOT resolve when input is removed, multiple COPC, hyperalgesia and multisite pain present

What is characteristic of bottom up nociplastic pain

Female > Male, late onset (adult), NO family history of pain, moderate psychological comorbidity, low allodynia, pain DOES resolve when input is removed, multiple COPC, hyperalgesia and multisite pain present

What is nociceptive pain

Pain from ACTUAL/THREATENED damage

What is neuropathic pain

Caused by LESION/DISEASE of somatosensory system

What is nociplastic pain

Pain WITHOUT damage

What is MG30

Chronic pain; lasting >3 mo

Symptoms of chronic pain

Persistent pain, fatigue, stiffness, sleep problems, mood change, decreased mobility, sensitivity to touch, appetite change, cognitive difficulties, social withdrawal

What are the first line drugs to treat neuropathic pain

TCA, SNRI, gabapentinoids

What are the second line drugs to treat neuropathic pain

Topical agents and weak opioids

What are the third line drugs to treat neuropathic pain

Strong opioids, Botox, Spinal cord stimulation, deep brain stimulation, targeted intrathecal drug delivery, rTMS and motor cortex stimulation

Mechanism of tricyclic antidepressants

Monoamine reuptake inhibition + Na channel blockade + anticholinergic

SNRI mechanism of action

5-HT and NE reuptake inhibition

Gabapentinoids mechanism of action

Bind to a2delta subunit of voltage-gated calcium channels, decreasing neurotransmitter release.