Textbook of Personalized Medicine - Second Edition [2015]

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Clinical diagnosis of type of pain & cause

Acute inflammatory pain

Resonse to common analgesics

Chronic Yes pain

Testing for conditioned pain modulation

No

Peripheral neuropathic pain: select drug according to subtype & mechanism

Central neuropathic pain: antiepileptics, antidepressants

Non-pharmacologic: TENS, TMS, etc

Adequate relief

No relief

No relief with drugs

Spinal cord stimulation Motor cortex stimulation Deep brain stimulation

No relief

Multidisciplinary approaches

Abbr: TENS= Transcutaneous electrical nerve stimulation; © Jain PharmaBiotech TMS= Transcranial magnetic stimulation

Fig. 12.7 An algorithm for personalized management of pain

Table 12.9 Personalized management of neuropathic pain based on mechanism

Mechanism Diagnostic features Molecular targets Drugs
Altered expression
of sodium
channels

Spontaneous pain, paresthesias

Na channels sensitive to tetrodotoxin

Local anesthetics
antiepileptics
antiarrhythmics
Tricyclic antidepressants
Specifi c Na
channels

Spontaneous pain Tetrodotoxin resistant Na channels

Selective blockers a

Central
sensitization

Hyperalgesia NMDA receptor NMDA antagonist a Glycine site antagonists a NK1 receptor antagonist a nNOS inhibitors a

NK 1 receptor
nNOS
Protein kinase
Protein kinase inhibitors a
Peripheral
sensitization

Hyperalgesia to nociceptive stimuli

Vanilloid receptor Capsaicin Cannabinoid receptor CB1 CB1 agonists a Hyperalgesia to thermal stimuli

Neurokinin 1 receptor Neurokinin 1 receptor antagonist a Neurogenic infl ammation

Nerve growth factor Nerve growth factor
antagonists a
Sympathetic
activity

Spontaneous pain Adrenergic receptors Guanethidine, clonidine
Nerve growth factor (NGF) NGF antagonists a^
Reduced
inhibition

Hyperalgesia Opioid receptors, GABA transaminase, NK 1, adenosine, purine, kainite, cholecystokinin, acetyl choline (nicotinic)

Morphine, gabapentin

Personalized Management of Pain