200
Views
33
CrossRef citations to date
0
Altmetric
Review

New targets for neuropathic pain therapeutics

&
Pages 685-698 | Published online: 05 Aug 2005

Bibliography

  • JULIUS D, BASBAUM AI: Molecular mechanisms of nociception. Nature (2001) 413(6852):203–210.
  • •An excellent review of basic pain mechanisms.
  • SCHOLZ J, WOOLF CJ: Can we conquer pain? Nat. Neurosci. (2002) 5(Suppl.):1062–1067.
  • WOOLF CJ, SALTER MW: Neuronal plasticity: increasing the gain in pain. Science (2000) 288(5472):1765–1769.
  • SMITH PA: Neuropathic Pain: Drug Targets for Current and Future Interventions. Drug News Perspect. (2004) 17( ):5–17.
  • UEDA H, RASHID MH: Molecular mechanism of neuropathic pain. Drug News Perspect. (2003) 16(9):605–613.
  • •Reviews the preclinical models that support our current understanding of NeP mechanisms.
  • DWORKIN RH: An overview of neuropathic pain: syndromes, symptoms, signs, and several mechanisms. Clin. J. Pain (2002) 18(6):343–349.
  • PRIEST TD, HOGGART B: Chronic pain: mechanisms and treatment. Curr. Opin. Pharmacol (2002) 2(3):310–315.
  • WOOLF CJ, MANNION RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet (1999) 353(9168):1959–1964.
  • WOOLF CJ: Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci. (2004) 74(21):2605–2610.
  • ••Concise review of the mechanismsunderlying NeP.
  • MOGIL JS, CRAGER SE: What should we be measuring in behavioral studies of chronic pain in animals? Pain (2004) 112(1-2):12–15.
  • SUNG YJ, AMBRON RT: Pathways that elicit long-term changes in gene expression in nociceptive neurons following nerve injury: contributions to neuropathic pain. NeuroL Res. (2004) 26(2):195–203.
  • WATKINS LR, MILLIGAN ED, MATER SF: Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv. Exp. Med. Bid. (2003) 521:1–21.
  • ••Review summarising the predinical evidence for glial regulation of NeP and potential pharmacological approaches.
  • WIESELER-FRANK J, MATER SF, WATKINS LR: Glial activation and pathological pain. Neurochem. Int. (2004) 45(2-3):389–395.
  • DELEO JA, TANGA FY, TAWFIK VL: Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist (2004) 10(1):40–52.
  • LAI J, HUNTER JC, PORRECA F: The role of voltage-gated sodium channels in neuropathic pain. Curr. Opin. NeurobioL (2003) 13(3):291–297.
  • BIRCH PJ, DEKKER LV, JAMES IF, SOUTHAN A. CRONK D: Strategies to identify ion channel modulators: current and novel approaches to target neuropathic pain. Drug Disc. Today (2004) 9(9):410–418.
  • ALTIER C, ZAMPONI GW: Targeting Ca2+ channels to treat pain: T-type versus N-type. Trends Pharmacol Sci. (2004) 25(9):465–470.
  • SABIDO-DAVID C, FARAVELLI L, SALVATI P: The therapeutic potential of Na+ and Ca2+ channel blockers in pain management. Expert Opin. Invest. Drugs (2004) 13(10):1249–1261.
  • ••Excellent review of predinical and clinicalevidence supporting a role for ion channels in chronic pain.
  • LAI J, PORRECA F, HUNTER JC, GOLD MS: Voltage-gated sodium channels and hyperalgesia. Ann. Rev. Pharmacol lbxicol. (2004) 44:371–397.
  • GOLD MS, WEINREICH D, KIM CS et al.: Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J. Neurosci. (2003) 23(1):158–166.
  • COWARD K, PLUMPTON C, FACER P et al.: Immunolocalization of SNS/PN3 and NaN/5N52 sodium channels in human pain states. Pain (2000) 85(1-2):41–50.
  • LAI J, GOLD MS, KIM CS et al.: Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8. Pain (2002) 95(1–2):143–152.
  • ••Demonstrates that antisense knockdown of Nav1.8 reverses pain behaviour in the rat SNL model of NeP.
  • BLACK JA, CUMMINS TR, PLUMPTON C et al.: Upregulation of asilent sodium channel after peripheral, but not central, nerve injury in DRG neurons. Neurophysiol (1999) 82(5):2776–2785.
  • KIM CH, OH Y, CHUNG JM, CHUNG K: The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. Md. Brain Res. (2001) 95(1-2):153–161.
  • DIB-HAJJ SD, FJELL J, CUMMINS TR et al.: Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain (1999) 83(3):591–600.
  • HAINS BC, SAAB CY, KLEIN JP, CRANER MJ, WAXMAN SG: Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J. Neurosci. (2004) 24(20):4832–4839.
  • •Inappropriate expression of Nav1.3 is linked to mechanisms contributing to NeP following rat nerve injury.
  • COWARD K, AITKEN A, POWELL A et al.: Plasticity of TTX-sensitive sodium channels PNI and brain III in injured human nerves. Neuroreport (2001) 12(3):495–500.
  • CHEN YH, DALE TJ, ROMANOS MA et al.: Cloning, distribution and functional analysis of the Type III sodium channel from human brain. Eur. j Neurosci. (2000) 12(12):4281–4289.
  • •Nav1.3 is expressed throughout the adult CNS in humans suggesting a physiological role.
  • HEINKE B, BALZER E, SANDKUHLER J: Pre- and postsynaptic contributions of voltage-dependent Ca2+ channels to nociceptive transmission in rat spinal laminal neurons. Eur. J. Neurosci. (2004) 19(1):103–111.
  • SAEGUSA H, KURIHARA T, ZONG S et al.: Suppression of inflammatory and neuropathic pain symptoms in mice lacking the N-type Ca2+ channel. EMBO J. (2001) 20(10):2349–2356.
  • MATTHEWS EA, DICKENSON AH: Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy. Pain (2001) 92(1-2):235–246.
  • MILJANICH GP: Ziconotide: Neuronal calcium channel blocker for treating severe chronic pain. Curr. Med. Chem. (2004) 11(23):3029–3040.
  • SNUTCH T, FENG Z P, BELARDETTI F et al.: Novel N-type calcium channel blockers efficacious in animal models of chronic pain. Abstracts of Papers American Chemical Society (2003) 226 Meet.(MEDI 6):Pt. 2.
  • KHOSRAVANI H, ALTIER C, SIMMS B et al.: Gating effects of mutations in the Ca(v)3.2 T-type calcium channel associated with childhood absence epilepsy. J. Biol. Chem. (2004) 279(11):9681–9684.
  • TALLEY EM, CRIBBS LL, LEE JH et al.: Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. Neurosci. (1999) 19(0:1895–1911.
  • DOGRUL A, GARDELL LR, OSSIPOV MH et al.: Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain (2003) 105(1-2):159–168.
  • FLATTERS SJ, BENNETT GJ: Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain (2004) 109(1-2):150–161.
  • BOURINET E, ALLOUI A, MONTEIL A et al.: Silencing of the Ca(v)3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J. (2005) 24(2):315–324.
  • ••Eloquent antisense knockdown studydemonstrating the relevance of Cav3.2 as a target for NeP.
  • KIM D, PARK D, CHOI S et al: Thalamic control of visceral nociception mediated by T-type Ca2+ channels. Science (2003) 302(5642):117–119.
  • CHEN C-C, LANIPING KG, NUNO DW et al.: Abnormal coronary function in mice deficient in a-1H T-type Ca2+ channels. Science (2003) 302(5649):1416–1418.
  • ARIKKATH J, CAMPBELL KP: Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr. Opin. Neurobiol (2003) 13(3):298–307.
  • LUO ZD, CALCUTT NA, HIGUERA ES et al.: Injury type-specific calcium channel alpha(2)delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. Pharmacol Exp. Ther. (2002) 303(3):1199–1205.
  • INOUE M, RASHID MH, FUJITA R et al.: Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat. Med. (2004) 10(7):712–718.
  • LI CY, SONG YH, HIGUERA ES, LUO ZD: Spinal dorsal horn calcium channel alpha(2)delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J. Neurosci. (2004) 24(39):8494–8499.
  • LI C, FENG G, LUO Z: Calcium channel alpha2delta - 1 subunit is a molecular determinant of pain behaviors: Evidences from injury - free transgenic mice. Program No. 64.9.2004 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience (2004)
  • FARRAR JT, YOUNG JP, LANIOREAUX L, WERTH JL, POOLE RNI: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain (2001) 94(2):149–158.
  • DWORKIN RH, CORBIN AE, YOUNG JP et al.: Pregabalin for the treatment of postherpetic neuralgia-A randomized, placebo-controlled trial. Neurology (2003) 60(8):1274–1283.
  • BRYANS JS, WUSTROW DJ: 3-substituted GABA analogs with central nervous system activity: A review. Med. Res. Rev. (1999) 19(2):149–177.
  • BRANIWELL SR, COX PJ, MELROSE H et al.: The analgesic actions of pregabalin are mediated through its binding to the a2d -1 subunit of voltage gated calcium channels. Program No. 523.19. 2004 Abstract Waver/Itinerary Planner. Washington, DC: Society for Neuroscience (2004)
  • ••First direct evidence demonstrating thatthe analgesic actions of gabapentin and pregabalin are dependent upon their binding to the a28–1 subunit of VGCCs.
  • WANG M, OFFORD J, OXENDER DL, SU TZ: Structural requirement of the calcium-channel subunit alpha2delta for gabapentin binding. Biochem. (1999) 342(Pt 2):313–320.
  • MELROSE HM, FIELD MJ, CARNELL P et al.: Neuroanatomical distribution of gabapentin and MI pregabalin binding in mutant a2d - 1 mice. No. 523.18. 2004 Abstract Waver/Itinerary Planner. Washington, DC: Society for Neuroscience (2004)
  • HUDSON LJ, BEVAN S, WOTHERSPOON G et al.: VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. R. J. Neurosci. (2001) 13(11):2105–2114.
  • TYMPANIDIS P, CASULA MA, YIANGOU Yet al.: Increased vanilloid receptor VR1 innervation in vulvodynia. Eur. J. Pain (2004) 8(2):129–133.
  • HONG S, WILEY JW: Early painful diabetic neuropathy is associated with differential changes in the expression and function of vanilloid receptor 1.1 Biol. Chem. (2005) 280(1):618–627.
  • SZALLASI k Vanilloid (capsaicin) receptors in health and disease. Am. J. Clin. Pathol (2002) 118(1):110–121.
  • RASHID MH, INOUE M, BAKOSHI S, UEDA H: Increased expression of vanilloid receptor 1 on myelinated primary afferent neurons contributes to the antihyperalgesic effect of capsaicin cream in diabetic neuropathic pain in mice. J. Pharmacol Exp. Ther. (2003) 306(2):709–717.
  • WALKER KM, URBAN L, T SJ et al.: The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain. J. Pharmacol Exp. Ther. (2003) 304(1):56–62.
  • GAVVA N, TANIIR R, QU Y et al: ANIG 9810, (E)-3-(4-t-butylpheny1)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-Aacrylamide, a novel vanilloid receptor 1 (TRPV1) antagonist with anti-hyperalgesic properties. J. Pharmacol Exp. Ther. (2005) 313(2):474–484.
  • ALESSANDRI-HABER N, DINA OA, YEH JJ et al.: Transient Receptor Potential Vanilloid 4 Is Essential in Chemotherapy-Induced Neuropathic Pain in the Rat. I. (2004) 24(18):4444–4452.
  • GAUDET AD, WILLIAMS SJ, HWI LP, RANIER MS: Regulation of TRPV2 by axotomy in sympathetic, but not sensory neurons. Brain Res. (2004) 1017(1-2):155–162.
  • DUNN PM, ZHONG Y, K G: P2X receptors in peripheral neurons. Prog-. Neurobiol (2001) 65(2):107–134.
  • NORTH RA: The P2X3 subunit: a molecular target in pain therapeutics. Curr. Opin. Invest. Drugs (2003) 4(7):833–840.
  • HONORE P, KAGE K, MIKUSA J et al.: Analgesic profile of intrathecal P2X(3) antisense oligonucleotide treatment in chronic inflammatory and neuropathic pain states in rats. Pain (2002) 99(1-2):11–19.
  • BARCLAY J, PATEL S, DORN G et al.: Functional downregulation of P2X3 receptor subunit in rat sensory neurons reveals a significant role in chronic neuropathic and inflammatory pain. J. Neurosci. (2002) 22(18):8139–8147.
  • ••Antisense knockdown of P2X3Rs reversespain behaviour in the rat PNL model of NeP.
  • DORN G, PATEL S, N G et al: A relieves chronic neuropathic pain. Nud Acid. Res. (2004) 32(5):e49.
  • MCGARAUGHTY S, WISMER CT, ZHU CZ et al: Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration. Br. J. Pharmacol (2003) 140(8):1381–1388.
  • INOUE K, TSUDA M, KOIZUMI S: ATP- and adenosine-mediated signaling in the central nervous system: Chronic pain and microglia: Involvement of the ATP receptor P2X(4). j Pharmacol Sci. (2004) 94(2):112–114.
  • TSUDA M, SHIGEMOTO-MOGAMI Y, KOIZUMI S et al.: P2X(4) receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature (2003) 424(6950):778–783.
  • ••Antisense study demonstrating thatknockdown of microglial P2X4Rs reverses spinal nerve injury-induced NeP.
  • AHMAD S, DRAY A: Novel G protein-coupled receptors as pain targets. Curr. Opin. Invest. Drugs (2004) 5(1):67–70.
  • RICE AS, FARQUHAR-SMITH WP, NAGY I: Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostaglandins Leukot. Essent. Y Acids (2002) 66(2-3):243–256.
  • WALKER JM, HUANG SM: Endocannabinoids in pain modulation. Prostaglandins Leukot. Essent. Fatty Acids (2002) 66(2-3):235–242.
  • BRIDGES D, AHMAD K, RICE AS: The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. Br. J. Pharmacol (2001) 133(4):586–594.
  • FOX A, KESINGLAND A, GENTRY C et al.: The role of central and peripheral Cannabinoidl receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. N (2001) 92(1-2):91–100.
  • LIM G, SUNG B, JI RR, MAO J: Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain (2003) 105(1-2):275–283.
  • SCOTT DA, WRIGHT CE, ANGUS JA: Evidence that CB-1 and CB-2 cannabinoid receptors mediate antinociception in neuropathic pain in the rat. Pain (2004) 109(1-2):124–131.
  • ULUGOL A. KARADAG HC, IPCI Y, TAMER M, DOKMECI I: The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neurosci. Lett. (2004) 371(2-3):167–170.
  • DOGRUL A, GUL H, AKAR A et al.: Topical cannabinoid antinociception: synergy with spinal sites. Pain (2003) 105(1-2):11–16.
  • •Support for a peripherally restricted CB1 agonist approach for NeP.
  • IBRAHIM MM, DENG H, ZVONOK A et al.: Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc. Natl Acad. Sci. USA (2003) 100(18):10529–10533.
  • ELMES SJ, JHAVERI MD, SMART D, KENDALL DA, CHAPMAN V: Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naive rats and in rat models of inflammatory and neuropathic pain. Eur. j Neurosci. (2004) 20(9):2311–2320.
  • WALTER L, FRANKLIN A, WITTING A et al.: Nonpsychotropic cannabinoid receptors regulate microglial cell migration. Neurosci. (2003) 23(4):1398–1405.
  • BOGER DL, SATO H, LERNER AE et al: Exceptionally potent inhibitors of fatty acid amide hydrolase: the enzyme responsible for degradation of endogenous oleamide and anandamide. Proc. Natl Acad. Sci. USA (2000) 97(10):5044–5049.
  • PETRILLO P, ANGELICI O, M S et al.: Evidence for a selective role of the delta-opioid agonist [8R-(4bS*,8a alpha,8a beta,12b beta)]7,10-dimethy1-1-methoxy-11-(2-methylpropypoxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo12,3-ghsoquinoline hydrochloride (SB-235863) in blocking hyperalgesia associated with inflammatory and neuropathic pain s. J. Pharmacol Exp. Ther. (2003) 307(3):1079–1089.
  • •Potent, selective delta opioid receptor agonist reverses pain behaviour in the Seltzer model of NeP without effects on gastrointestinal transit and motor coordination.
  • MORINVILLE A, CAHILL CM, KIEFFER B, COLLIER B, BEAUDET A: Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain. Pain (2004) 109(3):266–273.
  • CAHILL CM, MORINVILLE A, HOFFERT C, O'DONNELL D, BEAUDET A: Up-regulation and trafficking of delta opioid receptor in a model of chronic inflammation: implications for pain control. Pain (2003) 101(1-2):199–208.
  • STONE LS, VULCHANOVA L, RIEDL MS et al.: Effects of peripheral nerve injury on delta opioid receptor (DOR) immunoreactivity in the rat spinal cord. Neurosci. Lett. (2004) 361(1-3):208–211.
  • SHEARDOWN M, MESSAGER S, MATHEWS E et al.: Knockout of GPRT92 reveals key role in neuropathic and acute pain. Program No. 64.16 2004 Abstract Waver/Itinerary Planner. Washington, DC: Society for Neuroscience (2004)
  • FUNDYTUS ME: Glutamate receptors and nociception: implications for the drug treatment of pain. CNS Drugs (2001) 15(1):29–58.
  • NEUGEBAUER V CHEN PS, WILLIS WD: Groups II and III metabotropic glutamate receptors differentially modulate brief and prolonged nociception in primate STT cells. A (2000) 84(6):2998–3009.
  • MILLS CD, FULLWOOD SD, HULSEBOSCH CE: Changes in metabotropic glutamate receptor expression following spinal cord injury. Exp. Neurol (2001) 170(2):244–257.
  • CHIECHIO S, CARICASOLE A, BARLETTA E et al: L-Acetylcarnitine induces analgesia by selectively up-regulating mG1u2 metabotropic glutamate receptors. Md. Pharmacol. (2002) 61(5):989–996.
  • SIMMONS RM, WEBSTER AA, KALRA AB, IYENGAR S: Group II mGluR receptor agonists are effective in persistent and neuropathic pain models in 696 s. PharmacoL Biochem. Behav. (2002) 73(2):419–427.
  • DONG X, HAN S, ZYLKA MJ, SIMON MI, ANDERSON DJ: A diverse family of GPCRs expressed in c subsets of nociceptive sensory neurons. Cell (2001) 106(5):619–632.
  • LEMBO PM, GRAZZINI E, I T et al.: Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nat. Neurosci. (2002) 5(3):201–209.
  • •References 92,93 describe a e GPCR family some of which are exclusively expressed in sensory neurons.
  • GRAZZINI E, PUMA C, ROY MO et al:Sensory neuron-specific receptor activation elicits central and peripheral nociceptive effects in rats. Proc. NatL Acad. Sci. USA (2004) 101(18):7175–7180.
  • SHINOHARA T, HARADA M, OGI K et al.: Identification of a G protein-coupled receptor specifically responsive to beta-alanine. J. BioL Chem. (2004) 279(22):23559–23564.
  • ZYLKA MJ, RICE FL, ANDERSON DJ: Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron (2005) 45(1):17–25.
  • ZYLKA MJ, DONG X, H WELL AL, ANDERSON DJ: Atypical expansion in mice of the sensory neuron-specific Mrg G protein-coupled receptor family. Proc. Natl. Acad. Sci. USA (2003) 100(17):10043–10048.
  • BONINI JA, JONES KA, ADHAM N et al.: Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J. BioL Chem. (2000) 275(50):39324–39331.
  • GARDELL LR, BERTOZZI F, Y NM et al.: Efficacy of novel selective neuropeptide FF receptor s in animal models of neuropathic and inflammatory pain. Program No. 629.6 2004 Abstract Waver/Itinerary Planner. Washington, DC: Society for Neuroscience (2004).
  • ZENG Z, MCDONALD TP, WANG R, LIU Q, AUSTIN CP: Neuropeptide FF receptor 2 (NPFF2) is localized to pain-processing regions in the primate spinal cord and the lower level of the medulla oblongata. J. Chem. Neuroanat. (2003) 25(4):269–278.
  • GOUARDERES C, FAURA CC, ZAJAC JM: Rodent strain differences in the NPFF1 and NPFF2 receptor distribution and density in the central nervous system. Brain Res. (2004) 1014(1-2):61–70.
  • VERGE GM, MILLIGAN ED, MATER SF et al.: Fractakine (CX3CL1) and fractakine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur. J. Neurosci. (2004) 20(5):1150–1160.
  • MILLIGAN ED, ZAPATA V, R M et al.: Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur. j Neurosci. (2004) 20(9):2294–2302.
  • •Evidence to support a role for fractalkine and CX3CR1 in the development of NeP in animal models.
  • ABBADIE C, LINDIA JA, Y AM et al: Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl. Acad. Sci. USA (2003) 100(13):7947–7952.
  • •CCR2 knockout mice fail to develop allodynia in the rat PNL model.
  • NEILAN CL, KING T, ZHANG D et al: INCB3344, a CCR2 antagonist, prevents experimental neuropathic pain in mice. Program No. 17.4. 2004 Abstract Viewer/ Itinerary Planner. Washington, DC: Society for Neuroscience (2004)
  • ROUX PP, BLENIS J: ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. MoL BioL Rev. (2004) 68(2):320–344.
  • OBATA K, NOGUCHI K: MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci. (2004) 74(21):2643–2653.
  • CIRUELAA, DIXON AK, BRAMWELL S et al.: Identification of MEK1 as a novel target for the treatment of neuropathic pain. Br. J. PharmacoL (2003) 138(5):751–756.
  • OBATA K, YAMANAKA H, KOBAYASHI K et al.: E of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J. Neurosci. (2004) 24(45):10211–10222.
  • TSUDA M, MIZOKOSHI A, SHIGEMOTO-MOGAMI Y, I S, INOUE K: Activation of p38 mitogen-activated protein kinase in spinal hyperactive microglia contributes to pain y following peripheral nerve injury. Glia (2004) 45(1):89–95.
  • JIN SX, ZHUANG ZY, WOOLF CJ, JI RR: p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. I. (2003) 23(10):4017–4022.
  • •Activation of p38 kinase contributes to the development of NeP in predinical models.
  • INOUE K, KOIZUMI S, TSUDA M, SHIGEMOTO-MOGAMI Y: Signaling of ATP receptors in glia-neuron interaction and pain. Life Sci. (2003) 74(2-3):189–197.
  • GANJU P, HALL J: Potential applications of siRNA for pain therapy. Expert Opin. BioL Ther. (2004) 4(4):531–542.
  • •A thorough review outlining the potential of siRNA as a therapeutic option for chronic pain and the challenges that need to be overcome.
  • LAZORTHES Y, SAGEN J, SALLERIN B et al: Human chromaffin cell graft into the CSF for cancer pain management: a prospective Phase II clinical study. Pain (2000) 87(1):19–32.
  • EATON M: Cell therapy for neuropathic pain in spinal cord injuries. Expert. Opin. BioL Ther. (2004) 4(12):1861–1869.
  • LIN CR, WU PC, SHIH HC et al: Intrathecal spinal progenitor cell transplantation for the treatment of neuropathic pain. Cell Transplant. (2002) 11(1):17–24.
  • EATON MJ, PLUNKETT JA, MARTINEZ MA et al: Transplants of neuronal cells bioengineered to synthesize GABA alleviate chronic neuropathic pain. Cell Transplant. (1999) 8(1):87–101.
  • MCNEISH J: Embryonic stem cells in drug discovery. Nat. Rev. Drug Disc. (2004) 3(1):70–80.
  • HOFSTETTER CP, M NAV, LILJA JA et al.: Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nat. Neurosci. (2005) 8(3):346–353.
  • •References 114–119 highlight the potential for cell-based therapies.
  • POHL M, MEUNIER A, HAMON M, BRAZ J: Gene therapy of chronic pain. Curr. Gene Ther. (2003) 3(3):223–238.
  • •This review discusses gene therapy as an option for chronic pain therapy.
  • RO LS, CHEN ST, TANG LM, S JM: Effect ofNGF and anti-NGF on neuropathic pain in rats following chronic constriction injury of the sciatic nerve. Pain (1999) 79(2-3):265–274.
  • SOMMER C, LINDENLAUB T, TEUTEBERG P et al.: Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res. (2001) 913(1):86–89.
  • •These two studies demonstrate the potential for antibody-based therapy.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.