Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-06-11T17:12:37.041Z Has data issue: false hasContentIssue false
  • English
  • Français

Understanding Neuropathic Pain

Published online by Cambridge University Press:  07 November 2014

Walter Zieglgänsberger ,
Achim Berthele  and
Thomas R. Tölle
Get access Rights & Permissions [Opens in a new window]

Abstract

Neuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

Type
Review Article
Information
CNS Spectrums , Volume 10 , Issue 4 , April 2005 , pp. 298 - 308
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Merskey, H, Bogduk, N. Classification of Chronic Pain. Seattle, Wash: IASP Press; 1994.Google Scholar
2.Fields, HL, Baron, R, Rowbotham, MC. Peripheral neuropathic pain: an approach to management. In: Wall, P, Melzack, R, eds. Textbook of Pain. 4th ed. Edinburgh, Scotland: Churchill Livingstone; 1999:1523–1534.Google Scholar
3.Bennett, GJ. An animal model of neuropathic pain: a review. Muscle Nerve. 1993;16:1040–1048.CrossRefGoogle ScholarPubMed
4.Woolf, CJ, Salter, MW. Neuronal plasticity: increasing the gain in pain. Science. 2000;288:1765–1769.CrossRefGoogle ScholarPubMed
5.Torebjörk, HE, Lundberg, LE, LaMotte, RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol. 1992;448:765–780.CrossRefGoogle ScholarPubMed
6.Fields, HL, Rowbotham, M, Baron, R. Postherpetic neuralgia: irritable nociceptors and deafferentation. Neurobiol Dis. 1998;5:209–227.CrossRefGoogle ScholarPubMed
7.Derbyshire, SWG, Jones, AKB, Devani, P, et al.Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography. J Neurol Neurosurg Psychiatry. 1994;57:1166–1172.Google Scholar
8.Flor, H, Braun, C, Elbert, T, Birbaumer, N. Extensive reorganization of primary somatosensory cortex in chronic back pain patients. Neurosci Lett. 1997;224:5–8.CrossRefGoogle ScholarPubMed
9.Jones, AK, Derbyshire, SW. Reduced cortical responses to noxious heat in patients with rheumatoid arthritis. Ann Rheum Dis. 1997;56:601–607.CrossRefGoogle ScholarPubMed
10.Derbyshire, SWG. Meta-analysis of thirty-four independent samples studied using PET reveals a significantly attenuated central response to noxious stimulation in clinical pain patients. Curr Rev Pain. 1999;3:265–280.CrossRefGoogle ScholarPubMed
11.Ingvar, M. Pain and functional imaging. Philos Trans R Soc Lond B Biol Sci. 1999;354:1347–1358.Google Scholar
12.Rainville, P, Duncan, GH, Price, DD, Carrier, B, Bushnell, MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277:968–971.CrossRefGoogle Scholar
13.Tölle, TR, Kaufmann, T, Siessmeier, T, et al.Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann Neurol. 1999;45:40–47.3.0.CO;2-L>CrossRefGoogle Scholar
14.Casey, KL. Forebrain mechanisms of nociception and pain: analysis through imaging. Proc Natl Acad Sci U S A. 1999;96:7668–7674.Google Scholar
15.Casey, KL, Lorenz, J, Minoshima, S. Insights into the pathophysiology of neuropathic pain through functional brain imaging. Exp Neurol. 2003;184(suppl 1):S80–S88.CrossRefGoogle ScholarPubMed
16.Belmonte, C, Acosta, MC, Gallar, J. Neural basis of sensation in intact and injured corneas. Exp Eye Res. 2004;78:513–525.Google Scholar
17.Jensen, TS, Baron, R. Translation of symptoms and signs into mechanisms in neuropathic pain. Pain. 2003;102:1–8.CrossRefGoogle ScholarPubMed
18.Krarup, C. An update on electrophysiological studies in neuropathy. Curr Opin Neurol. 2003;16:603–612.CrossRefGoogle ScholarPubMed
19.Cruccu, G, Anand, P, Attal, N, et al.EFNS guidelines on neuropathic pain assessment. Eur J Neurol. 2004;11:153–162.Google Scholar
20.Backonja, MM, Serra, J. Pharmacologic management part 1: Better-studied neuropathic pain diseases. Pain Med. 2004;5(suppl 1):S28–S47.Google Scholar
21.Woolf, CJ, Bennett, GJ, Doherty, M, et al.Towards a mechanism-based classification of pain? Pain. 1998;77:227–229.CrossRefGoogle ScholarPubMed
22.Cantrell, AR, Catterall, WA. Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat Rev Neurosci. 2001;2:397–407.Google Scholar
23.Poliak, S, Peles, E. The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci. 2003;4:968–980.Google Scholar
24.Waxman, SG. Transcriptional channelopathies: an emerging class of disorders. Nat Rev Neurosci. 2001b;2:652–659.Google Scholar
25.Waxman, SG. Acquired channelopathies in nerve injury and MS. Neurology. 2001;56:1621–1627.Google Scholar
26.Shields, SD, Eckert, WA, Basbaum, AI. Spared nerve injury model of neuropathic pain in the mouse: a behavioral and anatomic analysis. J Pain. 2003;4:465–470.CrossRefGoogle Scholar
27.Lai, J, Porreca, F, Hunter, JC, Gold, MS. Voltage-gated sodium channels and hyperalgesia. Annu Rev Pharmacol Toxicol. 2004;44:371–397.CrossRefGoogle ScholarPubMed
28.Vanegas, HN, Schaible, HG. Prostaglandins and cycloxygenases in the spinal cord. Prog Neurobiol. 2001;64:327–363.Google Scholar
29.Harvey, RJ, Depner, UB, Wässle, H, et al.GlyR alpha 3: An essential target for spinal PGE(2)-mediated inflammatory pain sensitization. Science. 2004;304:884–887.Google Scholar
30.Katz, N. Coxibs: evolving role in pain management. Semin Arthritis Rheum. 2002;32(suppl 1):15–24.Google Scholar
31.Yasuda, H, Terada, M, Maeda, K, et al.Diabetic neuropathy and nerve regeneration. Prog Neurobiol. 2003;69:229–285.Google Scholar
32.Klein, JP, Waxman, SG. The brain in diabetes: molecular changes in neurons and their implications for end-organ damage. Lancet Neural. 2003;2:548–554.Google Scholar
33.Clapham, DE. TRP channels as cellular sensors. Nature. 2003;426(6966):517–524.Google Scholar
34.Cortright, DN, Szallasi, A. Biochemical pharmacology of the vanilloid receptor TRPV1–an update. Eur J Biochem. 2004;271:1814–1819.Google Scholar
35.Bianchi, L, Driscoll, M. Protons at the gate: DEG/ENaC ion channels help us feel and remember. Neuron. 2002;34:337–340.Google Scholar
36.Cervero, F, Laird, JMA. Understanding the signaling and transmission of visceral nociceptive events. J Neurobiol. 61;2004:45–54.Google Scholar
37.Kennedy, C, Assis, TS, Currie, AJ, Rowan, EG. Crossing the pain barrier: P2 receptors as targets for novel analgesics. J Physiol (Land). 2003;553:683–694.CrossRefGoogle ScholarPubMed
38.Chizh, BA, Illes, P. P2X receptors and nociception. Pharmacol Rev. 2001;53:553–568.Google Scholar
39.Sawynok, J. Liu, XJ. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol. 2003;69:313–340.Google Scholar
40.Sah, DWY, Ossipov, MH, Porreca, F. Neurotrophic factors as novel therapeutics for neuropathic pain. Nat Rev Drug Discov. 2003;2:460–472.Google Scholar
41.Kerr, BJ, Souslova, V, McMahon, SB, Wood, JN. A role for the TTX-resistant sodium channel Nav 1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport. 2001;12:3077–3080.Google Scholar
42.Roza, C, Laird, JMA, Souslova, V, Wood, JN, Cervero, F. The tetrodotoxin-resistant Na+ channel Nav 1.8 is essential for the expression of spontaneous activity in damaged sensory axons of mice. J Physiol (Lond). 2003;550:921–926.Google Scholar
43.Blum, R, Kafitz, KW, Konnerth, A. Neurotrophin-evoked depolarization requires the sodium channel Na(V)1.9. Nature. 2002;419:687–693.Google Scholar
44.Lu, B. Pro-region of neurotrophins: Role in synaptic modulation. Neuron. 2003;39:735–738.Google Scholar
45.Liu, HX, Hokfelt, T. The participation of galanin in pain processing at the spinal level. Trends Pharmacol Sci. 2002;23:468–474.CrossRefGoogle ScholarPubMed
46.Dickinson, T, Fleetwood-Walker, SM. VIP and PACAP: very important in pain? Trends Pharmacol Sci. 1999;20:324–329.Google Scholar
47.Sawynok, J. Topical and peripherally acting analgesics. Pharmacol Rev. 2003;55:1–20.Google Scholar
48.Pitcher, GM, Henry, JL. Nociceptive response to innocuous mechanical stimulation is mediated via myelinated afferents and NK-1 receptor activation in a rat model of neuropathic pain. Exp Neurol. 2004;186:173–197.Google Scholar
49.Fisher, K, Coderre, TJ, Hagen, NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management: Preclinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manage. 2000;20:358–373.Google Scholar
50.Danysz, W, Parsons, CG, Jirgensons, A, Kauss, V, Tillner, J. Amino-alkyl-cyclohexanes as a novel class of uncompetitive NMDA receptor antagonists. Curr Pharm Des. 2002;8:835–843.Google Scholar
51.Neto, FL, Schadrack, J, Platzer, S, Zieglgänsberger, W, Tölle, TR, Castro-Lopes, JM. Expression of metabotropic glutamate receptors mRNA in the thalamus and brainstem of monoarthritic rats. Mol Brain Res. 2000;81:140–154.Google Scholar
52.Salt, TE. Metabotropic glutamate (mGlu) receptors and nociceptive processing. Drug Dev Res. 2001;54:129–139.Google Scholar
53.Neugebauer, V. Metabotropic glutamate receptors–important modulators of nociception and pain behavior. Pain. 2002;98:1–8.Google Scholar
54.Hocking, G, Cousins, MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003;97:1730–1739.Google Scholar
55.Blackburn-Munro, G, Jensen, BS. The anticonvulsant retigabine attenuates nociceptive behaviours in rat models of persistent and neuropathic pain. Eur J Pharmacol. 2003;460:109–116.Google Scholar
56.Kornhuber, J, Bleich, S, Wiltfang, J, Maler, M, Parsons, CG. Flupirtine shows functional NMDA receptor antagonism by enhancing Mg2+ block via activation of voltage independent potassium channels. J Neural Transm. 1999;106:857–867.Google Scholar
57.Wickenden, AD, Roeloffs, R, McNaughton-Smith, G, Rigdon, GC. KCNQ potassium channels: drug targets for the treatment of epilepsy and pain. Exp Opin Ther Pat. 2004;14:457–469.CrossRefGoogle Scholar
58.Fundytus, ME. Glutamate receptors and nociception–implications for the drug-treatment of pain CNS Drugs. 2001;15:29–58.Google Scholar
59.Petrenko, AB. Yamakura, T. Baba, A. Shimoji, K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: A review. Anesth Analg. 2003;97:1108–1116.Google Scholar
60.Sandkühler, J. Learning and memory in pain pathways. Pain. 2000;88:113–118.Google Scholar
61.Ji, RR, Kohno, T, Moore, KA, Woolf, CJ. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26:696–705.Google Scholar
62.Fields, H. State-dependent opioid control of pain. Nat Rev Neurosci. 2004;5:565–575.Google Scholar
63.Wallace, VCJ, Cottrell, DF, Brophy, PJ, Fleetwood-Walker, SM. Focal lysolecithin-induced demyelination of peripheral afferents results in neuropathic pain behavior that is attenuated by cannabinoids. J Neurosci. 2003;23:3221–3233.CrossRefGoogle ScholarPubMed
64.Pertwee, RG. Cannabinoid receptors and pain. Prog Neurobiol. 2001;63:569–611.Google Scholar
65.Baker, D, Pryce, G, Giovannoni, G, Thompson, AJ. The therapeutic potential of cannabis. Lancet Neurol. 2003;2:291–298.Google Scholar
66.Iversen, L. Cannabis and the brain. Brain. 2003;126:1252–1270.Google Scholar
67.Cravatt, BF, Lichtman, AH. Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system Curr Opin Chem Biol. 2003;7:469–475.Google Scholar
68.Marsicano, G, Wotjak, CT, Azad, SC, et al.The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002;418:530–534.Google Scholar
69.Marsicano, G, Goodenough, S, Monory, K, et al.CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science. 2003;302:84–88.Google Scholar
70.Croxford, JL. Therapeutic potential of cannabinoids in CNS disease. CNS Drugs. 2003;17:179–202.CrossRefGoogle ScholarPubMed
71.Walter, L, Stella, N. Cannabinoids and neuroinflammation. Br J Pharmacol. 2004;141:775–785.CrossRefGoogle ScholarPubMed
72.Sandkühler, J. The organization and function of endogenous antinociceptive systems. Prog Neurobiol. 1996;50:49–81.Google Scholar
73.Woolf, CJ. Pain: Moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140:441–451.Google Scholar
74.McCleane, G. Cholecystokinin antagonists a new way to improve the analgesia from old analgesics? Curr Pharm Des. 2004;10:303–314.Google Scholar
75.Watkins, LR. Maier, SF. Glia: a novel drug discovery target for clinical pain. Nat Rev Drug Discov. 2003;2:973–985.Google Scholar
76.Banati, RB. Brain plasticity and microglia: is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation? J Physiol (Paris). 2002;96:289–299.Google Scholar
77.Julius, D, Basbaum, AI. Molecular mechanisms of nociception. Nature. 2001;413:203–210.Google Scholar
78.Mogil, JS, Yu, L, Basbaum, AI. Pain genes? Natural variation and transgenic mutants Annu Rev Neurosci. 2000;23:777–811.Google Scholar
79.Flor, H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002;1:182–189.Google Scholar
80.Flor, H. Cortical reorganisation and chronic pain: Implications for rehabilitation. J Rehab Med. 2003;35(suppl 41):66–72.CrossRefGoogle Scholar
81.Jones, AKP, Cunningham, VJ, Ha-Kawa, S, et al.Changes in central opioid receptor binding in relation to inflammation and pain in patients with rheumatoid arthritis. Br J Rheumatol. 1994;33:909–916.Google Scholar
82.Bencherif, B, Fuchs, PN, Sheth, R, Dannals, RF, Campbell, JN, Frost, JJ. Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET). Pain. 2002;99:589–598.CrossRefGoogle ScholarPubMed
83.Tölle, TR, Wester, HJ, Schwaiger, M, et al.The cingulate cortex in acute and chronic pain: H2150, 18FDG, and 11C-diprenorphine PET studies. In: Devor, M, Rowbotham, MC, Wiesenfeld-Hallin, Z, eds. Progress in Pain Research and Management. Seattle, Wash: IASP Press; 2000:507–513.Google Scholar
84.Willoch, F, Schindler, F, Wester, HE, et al.Central poststroke pain and reduced opioid receptor binding within pain processing circuitries: a [C-11]diprenorphine PET study. Pain. 2004;108:213–220.Google Scholar
85.Jänig, W, Baron, R. Complex regional pain syndrome: mystery explained? Lancet Neurol. 2003;2:687–69.Google Scholar
86.Willoch, F, Rosen, G, Tölle, TR, et al.Phantom limb pain in the human brain: Unraveling neural circuitries of phantom limb sensations using positron emission tomography. Ann Neurol. 2000;48:842–849.Google Scholar
87.Sindrup, SH, Jensen, TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83:389–400.Google Scholar
88.Bennett, MI, Simpson, KH. Gabapentin in the treatment of neuropathic pain. Palliat Med. 2004;18:5–11.Google Scholar
89.Dworkin, RH, Backonja, M, Rowbotham, MC, et al.Advances in neuropathic pain–diagnosis, mechanisms, and treatment recommendations. Arch Neurol. 2003;60:1524–1534.Google Scholar
90.Ploghaus, A, Becerra, L, Borras, C, Borsook, D. Neural circuitry underlying pain modulation: expectation, hypnosis, placebo. Trends Cogn Sci. 2003;7:197–200.Google Scholar