机制导向性神经病理性疼痛治疗新进展_West China Medical Journal

Authors：

 樊宇超 , 刘慧 ,  杨邦祥

四川大学华西医院麻醉科（成都 610041）;

Corresponding author：

杨邦祥, Email: 115826698@qq.com

Keywords：

神经病理性疼痛; 机制导向性; 治疗

DOI：

10.7507/1002-0179.20150277

Video：

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神经损伤后导致的疼痛具有不同的潜在机制，神经病理性疼痛的病理生理机制可反映在患者的个体表型上。针对患者个体临床表型的评估方法目前也开始应用于神经病理性疼痛的临床管理及研究当中。对患者个体的临床表型进行评估及划分亚组有助于鉴别其疼痛发生的潜在机制，进而筛选出可能从对该机制的靶向治疗获益的患者人群。

Citation： 樊宇超, 刘慧, 杨邦祥. 机制导向性神经病理性疼痛治疗新进展. West China Medical Journal, 2015, 30(5): 971-975. doi: 10.7507/1002-0179.20150277 Copy

1.	Baron R. Mechanisms of disease:neuropathic pain. A clinical perspective[J]. Nat Clin Pract Neurol, 2006, 2(2):95-106.
2.	Woodcock J, Witter J, Dionne RA. Stimulating the development of mechanism-based, individualized pain therapies[J]. Nat Rev Drug Discov, 2007, 6(9):703-710.
3.	Dworkin RH, Turk DC, Peirce-Sandner SA, et al. Research design considerations for confirmatory chronic pain clinical trials:IMMPACT recommendations[J]. Pain, 2010, 149(2):177-193.
4.	Katz J, Finnerup NB, Dworkin RH. Clinical trial outcome in neuropathic pain-relationship to study characteristics[J]. Neurology, 2008, 70(4):263-272.
5.	Woolf CJ, Max MB. Mechanism-based pain diagnosis-issues for analgesic drug development[J]. Anesthesiology, 2001, 95(1):241-249.
6.	Max MB. Towards physiologically based treatment of patients with neuropathic pain[J]. Pain, 1990, 42(2):131-137.
7.	von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms[J]. Neuron, 2012, 73(4):638-652.
8.	Baron R, Binder A, Wasner G. Neuropathic pain:diagnosis, pathophysiological mechanisms, and treatment[J]. Lancet Neurol, 2010, 9(8):807-819.
9.	Freeman R. Not all neuropathy in diabetes is of diabetic etiology:differential diagnosis of diabetic neuropathy[J]. Curr Diab Rep, 2009, 9(6):423-431.
10.	Xiao WH, Zheng H, Zheng FY, et al. Mitochondrial abnormality in sensory, but not motor, axons in paclitaxel-evoked painful peripheral neuropathy in the rat[J]. Neuroscience, 2011(199):461-469.
11.	Said G. Diabetic neuropathy:a review[J]. Nat Clin Pract Neurol, 2007, 3(6):331-340.
12.	Huang J, Zhang X, McNaughton PA. Modulation of temperature-sensitive TRP channels[J]. Semin Cell Dev Biol, 2006, 17(6):638-645.
13.	Kim HY, Park CK, Cho IH, et al. Differential changes in TRPV1 expression after trigeminal sensory nerve injury[J]. J Pain, 2008, 9(3):280-288.
14.	Ta LE, Bieber AJ, Carlton SM, et al. Transient receptor potential vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice[J]. Mol Pain, 2010, 6:5.
15.	Watabiki T, Kiso T, Kuramochi TA, et al. Amelioration of neuropathic pain by novel transient receptor potential vanilloid 1 antagonist AS1928370 in rats without hyperthermic effect[J]. J Pharmacol Exp Ther, 2011, 336(3):743-750.
16.	Weller K, Reeh PW, Sauer SK. TRPV1, TRPA1, and CB1 in the isolated vagus nerve-axonal chemosensitivity and control of neuropeptide release[J]. Neuropeptides, 2011, 45(6):391-400.
17.	Hoffmann T, Sauer SK, Horch RE, et al. Sensory transduction in peripheral nerve axons elicits ectopic action potentials[J]. J Neurosci, 2008, 28(24):6281-6284.
18.	Dib-Hajj SD, Cummins TR, Black JA, et al. Sodium channels in normal and pathological pain[J]. Annu Rev Neurosci, 2010(33):325-347.
19.	Mantyh PW, Koltzenburg M, Mendell LM, et al. Antagonism of nerve growth Factor-TrkA signaling and the relief of pain[J]. Anesthesiology, 2011, 115(1):189-204.
20.	Wu G, Ringkamp M, Murinson BB, et al. Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents[J]. J Neurosci, 2002, 22(17):7746-7753.
21.	Dobler T, Springauf A, Tovomik S, et al. TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones[J]. J Physiol, 2007, 585(3):867-879.
22.	Tulleuda A, Cokic B, Callejo G, et al. TRESK channel contribution to nociceptive sensory neurons excitability:modulation by nerve injury[J]. Mol Pain, 2011, 7:30.
23.	Kovalsky Y, Amir R, Devor M. Simulation in sensory neurons reveals a key role for delayed Na⁺ current in subthreshold oscillations and ectopic discharge:implications for neuropathic pain[J]. J Neurophysiol, 2009, 102(3):1430-1442.
24.	Xie RG, Zheng DW, Xing JL, et al. Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons[J]. PLoS One, 2011, 6(4):e18681.
25.	Amir R, Michaelis M, Devor M. Membrane potential oscillations in dorsal root ganglion neurons:role in normal electrogenesis and neuropathic pain[J]. J Neurosci, 1999, 19(19):8589-8596.
26.	Lee DH, Chang L, Sorkin LS, et al. Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated channel blockade alleviates mechanical allodynia and suppresses ectopic discharge in spinal nerve ligated rats[J]. J Pain, 2005, 6(7):417-424.
27.	Emery EC, Young GT, Berrocoso EM, et al. HCN2 ion channels play a central role in inflammatory and neuropathic pain[J]. Science, 2011, 333(648):1462-1466.
28.	Fukuoka T, Kobayashi K, Yamanaka H, et al. Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons[J]. J Comp Neurol, 2008, 510(2):188-206.
29.	Devor M. Sodium channels and mechanisms of neuropathic pain[J]. J Pain, 2006, 7(1Suppl 1):S3-S12.
30.	Thakor DK, Lin A, Matsuka Y, et al. Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy[J]. Mol Pain, 2009, 5:14.
31.	He XH, Zang Y, Chen X, et al. TNF-a contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury[J]. Pain, 2010, 151(2):266-279.
32.	Rose K, Ooi L, Dalle C, et al. Transcriptional repression of the M Channel subunit Kv7.2 in chronic nerve injury[J]. Pain, 2011, 152(4):742-754.
33.	Hains BC, Saab CY, Klein JP, et al. Altered sodium Channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury[J]. J Neurosci, 2004, 24(20):4832-4839.
34.	Ultenius C, Linderoth B, Meyerson BA, et al. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat[J]. Neurosci Lett, 2006, 399(1/2):85-90.
35.	Ohnami S, Tanabe M, Shinohara S, et al. Role of voltage-dependent calcium channel subtypes in spinal long-term potentiation of C-fiber-evoked field potentials[J]. Pain, 2011, 152(3):623-631.
36.	Favereaux A, Thoumine O, Bouali-Benazzouz R, et al. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103:role in pain[J]. EMBO J, 2011, 30(18):3830-3841.
37.	Fossat P, Dobremez E, Bouali-Benazzouz R, et al. Knockdown of L calcium channel subtypes:differential effects in neuropathic pain[J]. J Neurosci, 2010, 30(3):1073-1085.
38.	Brittain JM, Duarte DB, Wilson SM, et al. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²⁺ Channel complex[J]. Nat Med, 2011, 17(7):822-U260.
39.	Bauer CS, Nieto-Rostro M, Rahman W, et al. The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin[J]. J Neurosci, 2009, 29(13):4076-4088.
40.	Tran-Van-Minh A. Dolphin a C. The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2[J]. J Neurophysiol, 2010, 30(38):12856-12867.
41.	Sivilotti L, Woolf CJ. The Contribution of GABA_A and glycine receptors to central sensitization:disinhibition and touch-evoked allodynia in the spinal-cord[J]. J Neurophysiol, 1994, 72(1):169-179.
42.	Zhang H, Nei H, Dougherty PM. A p38 Mitogen-activated protein kinase-dependent mechanism of disinhibition in spinal synaptic transmission induced by tumor necrosis factor-alpha[J]. J Neurosci, 2010, 30(38):12844-12855.
43.	Kim HY, Lee KY, Lu Y, et al. Mitochondrial Ca²⁺ uptake is essential for synaptic plasticity in pain[J]. J Neurosci, 2011, 31(36):12982-12991.
44.	Sowa NA, Taylor-Blake B, Zylka MJ. Ecto-5'-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits[J]. J Neurosci, 2010, 30(6):2235-2244.
45.	Haanpaa M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment[J]. Pain, 2011, 152(1):14-27.
46.	Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment:revised 2009[J]. Eur J Neurol, 2010, 17(8):1010-1018.
47.	Baron R, Foerster M, Binder A. Subgrouping of patients with neuropathic pain according to pain-related sensory abnormalities:a first step to a stratified treatment approach[J]. Lancet Neurol, 2012, 11(11):999-1005.
48.	Di Stefano G, La Cesa S, Biasiotta A, et al. Laboratory tools for assessing neuropathic pain[J]. Neurol Sci, 2012, 33(Suppl 1):S5-S7.
49.	Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS):standardized protocol and reference values[J]. Pain, 2006, 123(3):231-243.
50.	Geber C, Klein T, Azad S, et al. Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS):A multi-centre study[J]. Pain, 2011, 152(3):548-556.
51.	Apkarian AV, Hashmi JA, Baliki MN. Pain and the brain:specificity and plasticity of the brain in clinical chronic pain[J]. Pain, 2011, 152(3, 1):S49-S64.
52.	Baliki MN, Schnitzer TJ, Bauer WR. Brain morphological signatures for chronic pain[J]. PLoS One, 2011, 6(10):e26010.
53.	Gustin SM, Peck CC, Wilcox SL, et al. Different pain, different brain:thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes[J]. J Neurosci, 2011, 31(16):5956-5964.
54.	Gwilym SE, Filippini N, Douaud G, et al. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty a longitudinal Voxel-Based morphometric study[J]. Arthritis Rheum, 2010, 62(10):2930-2940.
55.	Attal N, Fermanian C, Fermanian J, et al. Neuropathic pain:are there distinct subtypes depending on the aetiology or anatomical lesion?[J]. Pain, 2008, 138(2):343-353.
56.	Hatem SM, Attal N, Ducreux D, et al. Clinical, functional and structural determinants of central pain in syringomyelia[J]. Brain, 2010, 133(11):3409-3422.
57.	Baron R, Toelle TR, Gockel U, et al. A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia:differences in demographic data and sensory symptoms[J]. Pain, 2009, 146(1/2):34-40.
58.	Mahn F, Hüllemann P, Gockel U, et al. Sensory symptom profiles and co-morbidities in painful radiculopathy[J]. PLoS One, 2011, 6(5):e18018.
59.	Maier C, Baron R, Toelle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS):Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes[J]. Pain, 2010, 150(3):439-450.
60.	Simpson DM, Schifitto G, Clifford DB, et al. Pregabalin for painful HIV neuropathy a randomized, double-blind, placebo-controlled trial[J]. Neurology, 2010, 74(5):413-420.
61.	Freeman R, Baron R, Bouhassira D, et al. Identification of sensory symptom clusters in patients with neuropathic pain based on the neuropathic pain symptom inventory questionnaire[J]. J Pain, 2011, 12(4):P48.
62.	Yarnitsky D, Granot M, Nahman-Averbuch HA, et al. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy[J]. Pain, 2012, 153(6):1193-1198.
63.	von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms[J]. Neuron, 2012, 73(4):638-652.
64.	Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain:a review of recent clinical and experimental findings[J]. J Pain, 2009, 10(5):447-485.

1. Baron R. Mechanisms of disease:neuropathic pain. A clinical perspective[J]. Nat Clin Pract Neurol, 2006, 2(2):95-106.
2. Woodcock J, Witter J, Dionne RA. Stimulating the development of mechanism-based, individualized pain therapies[J]. Nat Rev Drug Discov, 2007, 6(9):703-710.
3. Dworkin RH, Turk DC, Peirce-Sandner SA, et al. Research design considerations for confirmatory chronic pain clinical trials:IMMPACT recommendations[J]. Pain, 2010, 149(2):177-193.
4. Katz J, Finnerup NB, Dworkin RH. Clinical trial outcome in neuropathic pain-relationship to study characteristics[J]. Neurology, 2008, 70(4):263-272.
5. Woolf CJ, Max MB. Mechanism-based pain diagnosis-issues for analgesic drug development[J]. Anesthesiology, 2001, 95(1):241-249.
6. Max MB. Towards physiologically based treatment of patients with neuropathic pain[J]. Pain, 1990, 42(2):131-137.
7. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms[J]. Neuron, 2012, 73(4):638-652.
8. Baron R, Binder A, Wasner G. Neuropathic pain:diagnosis, pathophysiological mechanisms, and treatment[J]. Lancet Neurol, 2010, 9(8):807-819.
9. Freeman R. Not all neuropathy in diabetes is of diabetic etiology:differential diagnosis of diabetic neuropathy[J]. Curr Diab Rep, 2009, 9(6):423-431.
10. Xiao WH, Zheng H, Zheng FY, et al. Mitochondrial abnormality in sensory, but not motor, axons in paclitaxel-evoked painful peripheral neuropathy in the rat[J]. Neuroscience, 2011(199):461-469.
11. Said G. Diabetic neuropathy:a review[J]. Nat Clin Pract Neurol, 2007, 3(6):331-340.
12. Huang J, Zhang X, McNaughton PA. Modulation of temperature-sensitive TRP channels[J]. Semin Cell Dev Biol, 2006, 17(6):638-645.
13. Kim HY, Park CK, Cho IH, et al. Differential changes in TRPV1 expression after trigeminal sensory nerve injury[J]. J Pain, 2008, 9(3):280-288.
14. Ta LE, Bieber AJ, Carlton SM, et al. Transient receptor potential vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice[J]. Mol Pain, 2010, 6:5.
15. Watabiki T, Kiso T, Kuramochi TA, et al. Amelioration of neuropathic pain by novel transient receptor potential vanilloid 1 antagonist AS1928370 in rats without hyperthermic effect[J]. J Pharmacol Exp Ther, 2011, 336(3):743-750.
16. Weller K, Reeh PW, Sauer SK. TRPV1, TRPA1, and CB1 in the isolated vagus nerve-axonal chemosensitivity and control of neuropeptide release[J]. Neuropeptides, 2011, 45(6):391-400.
17. Hoffmann T, Sauer SK, Horch RE, et al. Sensory transduction in peripheral nerve axons elicits ectopic action potentials[J]. J Neurosci, 2008, 28(24):6281-6284.
18. Dib-Hajj SD, Cummins TR, Black JA, et al. Sodium channels in normal and pathological pain[J]. Annu Rev Neurosci, 2010(33):325-347.
19. Mantyh PW, Koltzenburg M, Mendell LM, et al. Antagonism of nerve growth Factor-TrkA signaling and the relief of pain[J]. Anesthesiology, 2011, 115(1):189-204.
20. Wu G, Ringkamp M, Murinson BB, et al. Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents[J]. J Neurosci, 2002, 22(17):7746-7753.
21. Dobler T, Springauf A, Tovomik S, et al. TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones[J]. J Physiol, 2007, 585(3):867-879.
22. Tulleuda A, Cokic B, Callejo G, et al. TRESK channel contribution to nociceptive sensory neurons excitability:modulation by nerve injury[J]. Mol Pain, 2011, 7:30.
23. Kovalsky Y, Amir R, Devor M. Simulation in sensory neurons reveals a key role for delayed Na⁺ current in subthreshold oscillations and ectopic discharge:implications for neuropathic pain[J]. J Neurophysiol, 2009, 102(3):1430-1442.
24. Xie RG, Zheng DW, Xing JL, et al. Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons[J]. PLoS One, 2011, 6(4):e18681.
25. Amir R, Michaelis M, Devor M. Membrane potential oscillations in dorsal root ganglion neurons:role in normal electrogenesis and neuropathic pain[J]. J Neurosci, 1999, 19(19):8589-8596.
26. Lee DH, Chang L, Sorkin LS, et al. Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated channel blockade alleviates mechanical allodynia and suppresses ectopic discharge in spinal nerve ligated rats[J]. J Pain, 2005, 6(7):417-424.
27. Emery EC, Young GT, Berrocoso EM, et al. HCN2 ion channels play a central role in inflammatory and neuropathic pain[J]. Science, 2011, 333(648):1462-1466.
28. Fukuoka T, Kobayashi K, Yamanaka H, et al. Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons[J]. J Comp Neurol, 2008, 510(2):188-206.
29. Devor M. Sodium channels and mechanisms of neuropathic pain[J]. J Pain, 2006, 7(1Suppl 1):S3-S12.
30. Thakor DK, Lin A, Matsuka Y, et al. Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy[J]. Mol Pain, 2009, 5:14.
31. He XH, Zang Y, Chen X, et al. TNF-a contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury[J]. Pain, 2010, 151(2):266-279.
32. Rose K, Ooi L, Dalle C, et al. Transcriptional repression of the M Channel subunit Kv7.2 in chronic nerve injury[J]. Pain, 2011, 152(4):742-754.
33. Hains BC, Saab CY, Klein JP, et al. Altered sodium Channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury[J]. J Neurosci, 2004, 24(20):4832-4839.
34. Ultenius C, Linderoth B, Meyerson BA, et al. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat[J]. Neurosci Lett, 2006, 399(1/2):85-90.
35. Ohnami S, Tanabe M, Shinohara S, et al. Role of voltage-dependent calcium channel subtypes in spinal long-term potentiation of C-fiber-evoked field potentials[J]. Pain, 2011, 152(3):623-631.
36. Favereaux A, Thoumine O, Bouali-Benazzouz R, et al. Bidirectional integrative regulation of Cav1.2 calcium channel by microRNA miR-103:role in pain[J]. EMBO J, 2011, 30(18):3830-3841.
37. Fossat P, Dobremez E, Bouali-Benazzouz R, et al. Knockdown of L calcium channel subtypes:differential effects in neuropathic pain[J]. J Neurosci, 2010, 30(3):1073-1085.
38. Brittain JM, Duarte DB, Wilson SM, et al. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca²⁺ Channel complex[J]. Nat Med, 2011, 17(7):822-U260.
39. Bauer CS, Nieto-Rostro M, Rahman W, et al. The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin[J]. J Neurosci, 2009, 29(13):4076-4088.
40. Tran-Van-Minh A. Dolphin a C. The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2[J]. J Neurophysiol, 2010, 30(38):12856-12867.
41. Sivilotti L, Woolf CJ. The Contribution of GABA_A and glycine receptors to central sensitization:disinhibition and touch-evoked allodynia in the spinal-cord[J]. J Neurophysiol, 1994, 72(1):169-179.
42. Zhang H, Nei H, Dougherty PM. A p38 Mitogen-activated protein kinase-dependent mechanism of disinhibition in spinal synaptic transmission induced by tumor necrosis factor-alpha[J]. J Neurosci, 2010, 30(38):12844-12855.
43. Kim HY, Lee KY, Lu Y, et al. Mitochondrial Ca²⁺ uptake is essential for synaptic plasticity in pain[J]. J Neurosci, 2011, 31(36):12982-12991.
44. Sowa NA, Taylor-Blake B, Zylka MJ. Ecto-5'-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits[J]. J Neurosci, 2010, 30(6):2235-2244.
45. Haanpaa M, Attal N, Backonja M, et al. NeuPSIG guidelines on neuropathic pain assessment[J]. Pain, 2011, 152(1):14-27.
46. Cruccu G, Sommer C, Anand P, et al. EFNS guidelines on neuropathic pain assessment:revised 2009[J]. Eur J Neurol, 2010, 17(8):1010-1018.
47. Baron R, Foerster M, Binder A. Subgrouping of patients with neuropathic pain according to pain-related sensory abnormalities:a first step to a stratified treatment approach[J]. Lancet Neurol, 2012, 11(11):999-1005.
48. Di Stefano G, La Cesa S, Biasiotta A, et al. Laboratory tools for assessing neuropathic pain[J]. Neurol Sci, 2012, 33(Suppl 1):S5-S7.
49. Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS):standardized protocol and reference values[J]. Pain, 2006, 123(3):231-243.
50. Geber C, Klein T, Azad S, et al. Test-retest and interobserver reliability of quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS):A multi-centre study[J]. Pain, 2011, 152(3):548-556.
51. Apkarian AV, Hashmi JA, Baliki MN. Pain and the brain:specificity and plasticity of the brain in clinical chronic pain[J]. Pain, 2011, 152(3, 1):S49-S64.
52. Baliki MN, Schnitzer TJ, Bauer WR. Brain morphological signatures for chronic pain[J]. PLoS One, 2011, 6(10):e26010.
53. Gustin SM, Peck CC, Wilcox SL, et al. Different pain, different brain:thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes[J]. J Neurosci, 2011, 31(16):5956-5964.
54. Gwilym SE, Filippini N, Douaud G, et al. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty a longitudinal Voxel-Based morphometric study[J]. Arthritis Rheum, 2010, 62(10):2930-2940.
55. Attal N, Fermanian C, Fermanian J, et al. Neuropathic pain:are there distinct subtypes depending on the aetiology or anatomical lesion?[J]. Pain, 2008, 138(2):343-353.
56. Hatem SM, Attal N, Ducreux D, et al. Clinical, functional and structural determinants of central pain in syringomyelia[J]. Brain, 2010, 133(11):3409-3422.
57. Baron R, Toelle TR, Gockel U, et al. A cross-sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia:differences in demographic data and sensory symptoms[J]. Pain, 2009, 146(1/2):34-40.
58. Mahn F, Hüllemann P, Gockel U, et al. Sensory symptom profiles and co-morbidities in painful radiculopathy[J]. PLoS One, 2011, 6(5):e18018.
59. Maier C, Baron R, Toelle TR, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS):Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes[J]. Pain, 2010, 150(3):439-450.
60. Simpson DM, Schifitto G, Clifford DB, et al. Pregabalin for painful HIV neuropathy a randomized, double-blind, placebo-controlled trial[J]. Neurology, 2010, 74(5):413-420.
61. Freeman R, Baron R, Bouhassira D, et al. Identification of sensory symptom clusters in patients with neuropathic pain based on the neuropathic pain symptom inventory questionnaire[J]. J Pain, 2011, 12(4):P48.
62. Yarnitsky D, Granot M, Nahman-Averbuch HA, et al. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy[J]. Pain, 2012, 153(6):1193-1198.
63. von Hehn CA, Baron R, Woolf CJ. Deconstructing the neuropathic pain phenotype to reveal neural mechanisms[J]. Neuron, 2012, 73(4):638-652.
64. Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain:a review of recent clinical and experimental findings[J]. J Pain, 2009, 10(5):447-485.

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机制导向性神经病理性疼痛治疗新进展

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