neuropathic itch (2014)
TRANSCRIPT
Neuropathic itch
Peter Kamerman
PainSA Congress, Stellenbosch, South Africa, 2014
What is the definition of an itch?
What is the definition of an itch?
A sensation that causes the desire to scratch
Neurobiology of itch
Neurobiology of itch
Pain ItchScratchWithdrawal
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
TRPA1
Dorsal horn
Brain
Dorsal horn
Periphery
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: scratching
Adapted from: Ross, 2011
-
Scratch
X
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
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
Conclusions
Neuropathic itch:
Affects a significant proportion of people with a peripheral nerve lesion
Lack of treatment trials
Too many unanswered questions