NOCICEPTIVE PAINNOCICEPTIVE PAIN ( 組織傷害性疼痛 )

COX-II 有效

Sharpening- 尖銳痛Prickling- 酥麻痛 Scrawling- 蟻爬感Lightening- 閃電痛 Tingling- 墊墊的痛Burning- 燒灼感…………

1. Diabetic peripheral neuropathic pain ( DPNP) 糖尿病末梢神經疼痛

2. Post-herpetic neuralgia (PHN)疱疹後神經痛

Neuropathic pain

神經性疼痛

COX-II 無效

Pain Type-分成兩大類

急性疼痛 慢性疼痛

第三類第三類 ::合併組織傷害合併組織傷害 ++ 神經性疼痛神經性疼痛

1. 急性椎間盤突出 ~~

2. 癌症侵襲合併壓迫 ~~ ~~(NSAID 會有部分療效 )~~~

疼痛定義

• 痛覺異常 (Dysesthesia). • 感覺異常 (Paresthesia). • 觸痛症 (Allodynia).• 痛覺敏感 (Hyperalgesia).• 感覺過敏 (Hyperesthesia) .• 過度疼痛 (Hyperpathia).• 神經痛 (Neuralgia).• 神經炎 (Neuritis).• 神經燒灼痛 (Causalgia).

痛覺敏感 vs 觸痛症 Hyperalgesia vs. Allodynia

Martin, 1998.

Current Prescription Medication Use Among Patients Treated for Neuropathic Pain

Anticonvulsants 13%

Antidepressants/ mood stab. 4%

Opioids 4%

NSAIDs (include COX-2) 41%

Non-narcotic analgesics 21%

Tranquilizers 9%

Local anesthetics 6%

All other 2%

Medications with established efficacy represent a small proportion of prescriptions.

IMS global prescription data 4Q 2003 (n=143 million prescriptions).

疼痛路徑周邊敏感器 - 脊椎轉運站 - 中樞大腦站

Peripheral receptor

Spino-thalamic tract

Thalamic projection-->Cortex (Parietal lobe)

Pain

(small fiberfree ending)

五大疼痛機轉 --( 決定如何用藥 )

• 週邊敏感化(Peripheral sensitization )---NASID effective

• 異位放電(Ectopic discharges)---AEDs

• 中樞激活敏感(Central sensitization)---AEDs/Opioids

• 中樞重入(Central reorganization)---GABA/AEDs/Opioid

• 抑制消失(‘Loss of inhibitory controls)—TCAs

Attal, 1999; Woolf, 1999.

(I) Peripheral Sensitization

Noxious swelling/ damage

Descending Pathway

PeripheralNerve

Dorsal RootGanglion

C-Fiber

A-beta Fiber

A-delta Fiber

AscendingPathways

Dorsal Horn

Brain

Spinal Cord

Adapted with permission from WebMD Scientific American® Medicine.10

PGE2, (OA or RA pain)

Substance P,Glutamate. (Neuropathic pain)

CGRP, Serotonin (Migraine)

Non-epinephrine..(anxious pain)

N Free-ending

(2) Ectopic impulses(Na-K pumping imbalance)

(3) Central Sensitization(NMDA)

AMPA = -amino-3-hydroxy-5-methyl-4-isoazolepropionic acid; Mg+2 = magnesium ions; NK-1 = neurokinin-1 receptor; NMDA = N-methyl D-aspartate. Mannion RJ, Woolf CJ. Clin J Pain 2000 (in press).

Normal resting potential

Mg plug

AMPA = -amino-3-hydroxy-5-methyl-4-isoazolepropionic acid; Ca+2 = calcium ions; L-Arg = L-arginine; NK-1 = neurokinin-1 receptor; NMDA = N-methyl D-aspartate; NO = nitric oxide; NOS = nitric oxide synthase. Mannion RJ, Woolf CJ. Clin J Pain 2000 (in press).

(3) Central Sensitization

Ca++

Noxious stimulation

Mg unplug

{Glutamate-AMPA}------ {substance P- Neurokinin}