Neuropathic Pain08
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Transcript of Neuropathic Pain08
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NEUROPATHIC PAIN
R3 정고운
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I. Neuropathic Pain
Pain initiated or caused by a primary lesion or dysfunction of the nervous system
(eg, painful diabetic neuropathy, post-herpetic neuralgia)
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Symptom tactile allodynia(m/c) Constant burning pain Cramping /aching Hyperpathia, hyperalgesia Hyperesthesia
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PERIPHERAL NEUROPATHIC PAIN
Due to anatomical,chemical or biochemical changes to peripheral nervesExamples include: post-herpetic neuralgia,pain in HIV infections, trigeminal neuralgia, compression by a tumour , diabetic neuropathy, sciatica, post-surgery, following chemotherapy(eg vincristine), radiation
CENTRAL NEUROPATHIC PAIN
Due to pathophysiological changes in the brain or spinal chord ie the primarylesion is in the CNSExamples include phantom limb pain,pain following stroke, multiple sclerosis
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III. Pathophysiology
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Primary afferent neuronal mechanism
Ectopic activityvotage gated NA+ channels 의 비정상적 증식
(neuroma) → abnormal excitability → spontaneous sprouts → stimulate the connecting regenerative C-
fiber → erratic impulse generation → transmit to the
CNS → dysesthesia, such as tingling, itching,
electrifying sensitization
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Abnormal expression of Na+ channel- Increase density and up-regulation of Na channel(SNS(“sensory-nerve-specific, subtype α-Ⅲ(embryonic))
- action potential threshold ↓ & spontaneous ectopic discharge ↑- fast recovery following inactivation - repetitive firing of injured neuron was facilitated
at low threshold (ectopic impulse generation)
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Sensory-sympathetic coupling- noradrenaline released from near by sympathetic efferent fibers binds to α adrenoreceptors
on the injured afferent neuron & increased sensitivity
- causalgia - sympathetic block → pain 감소- sympathetic stimulus → pain 증가
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Ca channels in injured nerve endings - entry of Ca ion into the nerve endings N- or L type calcium channel -> calcitonin
gene related peptide from injured nerve endings
- CCBs are effective to block neuropathic pain
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Neuroimmune interaction - nerve injury → MØ → TNFα & IL1ß → ectopic activity, inflammatory hyperalgesia
- higher TNF α immuoreactivities
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Phenotypic change- DRG neuron- A-ß fiber (non-noxious) →substance P (pronociceptive) / neuropeptide (antinociceptive) 生
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Pathologic interaction c C & A-ß fiber - nerve injury → disruption of glial ensheathment → cross-excitation∴ A-ß fiber (tactile) ↔ C fiber (noxious)
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Spinal mechanism
Central reorganization- small-diameter aff.(C fiber) → superficial dorsal horn (lamina I/II) → noxious stimuli- large-diameter aff.(A-ß fiber) → deep dorsal horn (lamina III/IV) → tactile stimuli- nerve injury 시 C fiber degeneration & A-ß fiber growth to lamina I/II
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Disinhibition- inefficiency of endogenous inh. Sys.
continuous inhibitory control of brainstem↓
loss of A-δfiber induce GABAnergic inhibitory
interneuron apoptosis transynaptic neural degeneration (GABA receptor ↓, opioid receptor ↓)
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Central sensitization repetitive noxious stimulation leads to the
increased activities of asparate & glutamte at NMDA & neurokinin 1 receptor
increased inctracellular CA & activation of PKC → activate DHC, phosphorylation of NMDA rec. → causes decreased Mg blockade at phys.
resting potential exp. Of c-fos → neuropeptides → central
plasticity
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IV. Treatment
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Stimulation dependent pain (evoked pain) pph. sensitization : - local anesthetics( lidocaine patch 5%) - capsaicin abnormal exp. of Na channel - antiepileptic, anticonvulsant, anti
arrhythmic, TCA(amitriptyline) central sensitization - Na channel blocker, local anesthetics
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Stimmulous independent pain Paresthesia & dysesthesia : spont. firing of
A fiber→ Na channel blocker Peripheral sensitizaion, disinhibition,
causalgia→ local anesthetics, capsaicin, Na channel
blocker, gabapentin, baclofen, clonidine
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* Opiates
- - C fiber 에는 효과 & A-ß fiber 에는 효과 X
< 용량 >- neuropathic>>nociceptive- center ↑: effect↓- rotation 고려- morphine : 300mg, oxycodein : 240mg, methadone : 80mg (sustained-release) fentanyl : 100μg (transdermal)
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* α2 agonist
- opioid 와 작용 비슷 - sympathetic block
→ opioid 보다 효과적
< 용량 >- clonidine : transdermal patch → systemic delivery → intraspinal delivery- intraspinal delivery : hypotension 주의
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* NMDA antagonist
- NMDA ionopore : glutamate (nerve injury 시 ↑ ), Mg2+, glycine, polyamine binding → ionopore opening → Ca2+ influx
< 용량 >- ketamine : 2~6 mg/kg/d(IV), 100~500mg/d(orla)
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* COX inhibitor & PG receptor antagonis
- tissue injury 시 PG release ↑ - ketorolac,parecoxib
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* Na+ channel blocker
- nerve injury 시 ↑
< 용량 >- lamotrigine (choice) : ~400md/d- mexilletine : ~1200mg/d- lidocaine : 1~3mg/kg/h- non selective block
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*Ca2+ channel blocker
- L, N, P/Q, R ,T - high threshold : L(cell body & dendritie), N, P/Q, R (synaptic site) < 용량 >- ziconotide : #1 0.1μg/h, #2 0.2μg/h, #3 0.3μg/h, #4 0.6μg/h, #5 1.2 μg/h, #6 2.4 μg/h- non selective & dose limiting side effect
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*Gabapentin
- unknown mechanism
< 용량 >- starting dose : 900mg/d (#3) → 2700~3600mg/d
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*Antidepressant
- cathecholamine reuptake ↓ < 용량 > - by sleep disturbance & at bedtime - amitriptyline, doxepin >> nortriptyline, imipramine - starting dose : 10mg/d (>65) : 25mg/d (<65) → 200~300mg/d