Neuropathic itch (2014)
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Transcript of Neuropathic itch (2014)
Neurobiology of itch
Pruritoceptors are nociceptors
Adapted from: LaMotte et al., 2014
Non-pruritoceptive nociceptor (“pain fibres”)
Pruritoceptive nociceptor (“itch fibres”)
Neurobiology of itch
Non-pruritoceptive nociceptor (“pain fibres”)
Adapted from: Ross, 2011
HeatCapsaicinProtons
ColdMustard oil
Cinnamon oil
TRPA1TRPV
1
Nociceptor plasma
membrane
Depolarization Depolarization
ALGOGENS ALGOGENS
Neurobiology of itch
Pruritoceptive nociceptor (“itch fibres”)
Adapted from: Ross, 2011
Histamine Bradykinin BAM ChloroquineTryptase
PAR: Protease activated receptorMrgpr: Mas-related G protein-coupled receptor
H1R: Histamine receptorB2R: Bradykinin receptor
TRPA1TRPV1
HeatCapsaicinProtons
ColdMustard oil
Cinnamon oil
ALGOGENS ALGOGENS
PRURIGENS PRURIGENS PRURIGENS PRURIGENS
Neurobiology of itch
Robinson et al., 2013
Gastrin-releasing peptide (GRP)B-type natriuretic peptide (BNP)
TRPA1
Brain
Dorsal horn
Periphery
Neurobiology of itch
Modulation: morphine itch
Adapted from: Ross, 2011; Miyamoto & Patapoutian, 2011
Morphine - +MOR1 MOR1D
X
Neurobiology of itch
Modulation: alloknesis and hyperknesis
Adapted from: Ross, 2011; Miyamoto & Patapoutian, 2011
Flare
Wheal
Hyperalgesia
Hyperknesis(Enhanced itch induced by itch stimuli) Alloknesis(Itch induced by non-itch stimuli)
Histamine injection (itch)
Neurobiology of itch
Modulation: alloknesis
Adapted from: Ross, 2011; Miyamoto & Patapoutian, 2011
Itch projection neuron ItchPruritoceptive nociceptor
Touch projection neuron Touch
Touch receptor
Neurobiology of itch
Modulation: alloknesis
Adapted from: Ross, 2011; Miyamoto & Patapoutian, 2011
Itch projection neuron ItchPruritoceptive nociceptor
Touch projection neuron
Touch receptor
Alloknesis
Neuropathic itch
Itch
Peripheral nerve
Pruritoceptor
Definition
Itch as a direct consequence of a lesion or
disease affecting the somatosensory system
Neuropathic itch
Itch
Peripheral nerve
Pruritoceptor
Consequences of a lesion
no pain and no itch
itch without pain
pain without itch
pain with itch
Neuropathy Itch present Severe itch present
Keloid scars (with SF entrapment) 86% -
Post-herpetic neuralgia 30-65% 20-30%
Polyneuropathies 30% 10%
Traumatic nerve injury 20% 10%
Trigeminal neuralgia Occasionally -
For review: Binder et al., 2008
Epidemiology of neuropathic itch
Shaikh et al., 2012
Characteristics of symptomatic HIV-SN
Symptom Frequency (%)
Hot/Burning 48
Cramping 35
Itching 22
Cold/Freezing 17
Neuropathic itch
“My feet doctor, so itchy. I need to scratch all the time”
Binder et al., 2008; Dhand & Aminoff, 2014, Oaklander, 2011
Neuropathic itch
Characteristics
Chronic itch with:• Burning, pricking, tingling• Alloknesis• Hyperknesis
• Allodynia• Hypoaesthesia
Oaklander et al., 2002
Neuropathic itch
Itch with skin denervation: itch without painSkin biopsies from the forehead of a woman with post-herpetic neuralgia with itch
Unaffected area
Affected area
Oaklander et al., 2002
Neuropathic itch
Itch with skin denervation: itch without painSkin biopsies from the forehead of a woman with post-herpetic neuralgia
Neuropathic itch
Treatment
Type Examples
Non-pharmacological Education about itchNail-cuttingProtective garments
Pharmacological Gabapentin (itch following burns)
Anecdotal evidence5% lidocaine; Tacrolimus; Cortisone; Botulinium toxin Type A
Lamotrigine; Pregabalin; Carbamazepine; TCAs
Dhand & Aminoff, 2014; Stumpf & Stander, 2013; Oklander, 2012; Oaklander, 2011; Binder et al., 2008