NEUROPATHIC PAIN R3  정고운
I. Neuropathic Pain <ul><li>Pain initiated or caused by a primary lesion or dysfunction  of the nervous system  </li></ul>...
<ul><li>Symptom </li></ul><ul><li>tactile allodynia(m/c) </li></ul><ul><li>Constant burning pain </li></ul><ul><li>Crampin...
<ul><li>PERIPHERAL NEUROPATHIC PAIN </li></ul><ul><li>Due to anatomical,chemical or biochemical changes to peripheral nerv...
III. Pathophysiology
Primary afferent neuronal mechanism <ul><li>Ectopic activity votage gated NA+ channels 의 비정상적 증식 </li></ul><ul><li>(neurom...
<ul><li>Abnormal expression of Na +  channel - Increase density and up-regulation of Na channel(SNS(“sensory-nerve-specifi...
<ul><li>Sensory-sympathetic coupling - noradrenaline released from near by sympathetic efferent fibers binds to  α  adreno...
<ul><li>Ca channels in injured nerve endings </li></ul><ul><li>- entry of Ca ion into the nerve endings  </li></ul><ul><li...
<ul><li>Neuroimmune interaction  - nerve injury    -> MØ -> TNF α  & IL1ß   -> ectopic activity, inflammatory hyperalgesia...
<ul><li>Phenotypic change - DRG neuron - A-ß fiber (non-noxious)   ->substance P (pronociceptive)   / neuropeptide (antino...
<ul><li>Pathologic interaction c C & A-ß fiber   - nerve injury    -> disruption of glial ensheathment   -> cross-excitati...
Spinal mechanism <ul><li>Central reorganization - small-diameter aff.(C fiber)   -> superficial dorsal horn (lamina I/II) ...
<ul><li>Disinhibition -  inefficiency of endogenous inh. Sys. </li></ul><ul><li>continuous inhibitory control of brainstem...
<ul><li>Central sensitization </li></ul><ul><li>repetitive noxious stimulation leads to the increased activities of aspara...
IV. Treatment
 
<ul><li>Stimulation dependent pain (evoked pain) </li></ul><ul><li>pph. sensitization : </li></ul><ul><li>- local anesthet...
<ul><li>Stimmulous independent pain  </li></ul><ul><li>Paresthesia & dysesthesia : spont. firing of A fiber </li></ul><ul>...
 
* Opiates <ul><li>-  - C fiber 에는 효과  & A-ß fiber 에는 효과  X < 용량 > - neuropathic>>nociceptive - center ↑: effect↓ - rotatio...
*  α 2 agonist <ul><li>- opioid 와 작용 비슷 </li></ul><ul><li>- sympathetic block   -> opioid 보다 효과적  < 용량 > - clonidine : tra...
* NMDA antagonist <ul><li>- NMDA ionopore   : glutamate (nerve injury 시 ↑ ),   Mg 2+ , glycine, polyamine binding   -> ion...
* COX inhibitor & PG receptor antagonis <ul><li>- tissue injury 시  PG release ↑  - ketorolac,parecoxib </li></ul>
* Na +   channel blocker <ul><li>- nerve injury 시 ↑ < 용량 > - lamotrigine (choice) : ~400md/d - mexilletine : ~1200mg/d - l...
*Ca 2+   channel blocker <ul><li>- L, N, P/Q, R ,T  - high threshold    : L(cell body & dendritie),   N, P/Q, R (synaptic ...
*Gabapentin <ul><li>- unknown mechanism < 용량 > - starting dose : 900mg/d (#3)   -> 2700~3600mg/d </li></ul>
* Antidepressant <ul><li>- cathecholamine reuptake ↓   < 용량 >  - by sleep disturbance & at bedtime  - amitriptyline, doxep...
Upcoming SlideShare
Loading in …5
×

Neuropathic Pain08

811 views
745 views

Published on

Published in: Education, Health & Medicine
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
811
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
56
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Neuropathic Pain08

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

×