Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Targeting Neuropathic Pain: Pathobiology, Current Treatment and Peptidomimetics as a New Therapeutic Opportunity

Author(s): Maria Cristina Caroleo, Antonella Brizzi*, Maria De Rosa, Ankur Pandey, ">Luca Gallelli, Mariateresa Badolato, Gabriele Carullo and Erika Cione

Volume 27 , Issue 9 , 2020

Page: [1469 - 1500] Pages: 32

DOI: 10.2174/0929867326666190530121133

Price: $65


There is a huge need for pharmaceutical agents for the treatment of chronic Neuropathic Pain (NP), a complex condition where patients can suffer from either hyperalgesia or allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines include the use of tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors and anticonvulsants, beside the use of natural compounds and non-pharmacological options. Unfortunately, these drugs suffer from limited efficacy and serious dose-dependent adverse effects. In the last decades, the heptapeptide SP1-7, the major bioactive metabolite produced by Substance P (SP) cleavage, has been extensively investigated as a potential target for the development of novel peptidomimetic molecules to treat NP. Although the physiological effects of this SP fragment have been studied in detail, the mechanism behind its action is not fully clarified and the target for SP1-7 has not been identified yet. Nevertheless, specific binding sites for the heptapeptide have been found in brain and spinal cord of both mouse and rats. Several Structure-Affinity Relationship (SAR) studies on SP1-7 and some of its synthetic analogues have been carried out aiming to developing more metabolically stable and effective small molecule SP1-7-related amides that could be used as research tools for a better understanding of the SP1-7 system and, in a longer perspective, as potential therapeutic agents for future treatment of NP.

Keywords: Neuropathic, erythromelalgia, inflammation, antidepressants, anticonvulsants, opioids, cannabinoids, Substance P (SP).

Ji, R.R.; Xu, Z.Z.; Gao, Y.J. Emerging targets in neuroinflammation-driven chronic pain. Nat. Rev. Drug Discov., 2014, 13(7), 533-548.
[] [PMID: 24948120]
International Association for the Study of Pain (IASP) committee on taxonomy. Available at: . (Accessed Date: 25 Febuary, 2018)
Baron, R. Mechanisms of disease: neuropathic pain--a clinical perspective. Nat. Clin. Pract. Neurol., 2006, 2(2), 95-106.
[] [PMID: 16932531]
Torrance, N.; Smith, B.H.; Bennett, M.I.; Lee, A.J. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J. Pain, 2006, 7(4), 281-289.
[] [PMID: 16618472]
Costigan, M.; Scholz, J.; Woolf, C.J. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu. Rev. Neurosci., 2009, 32, 1-32.
[] [PMID: 19400724]
Ossipov, M.H.; Morimura, K.; Porreca, F. Descending pain modulation and chronification of pain. Curr. Opin. Support. Palliat. Care, 2014, 8(2), 143-151.
[PMID: 24752199]
Apkarian, A.V.; Hashmi, J.A.; Baliki, M.N. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain, 2011, 152(Suppl. 3), S49-S64.
[] [PMID: 21146929]
Tracey, I.; Bushnell, M.C. How neuroimaging studies have challenged us to rethink: is chronic pain a disease? J. Pain, 2009, 10(11), 1113-1120.
[] [PMID: 19878862]
Shulman, G.L.; Corbetta, M.; Buckner, R.L.; Fiez, J.A.; Miezin, F.M.; Raichle, M.E.; Petersen, S.E. Common blood flow changes across visual tasks: I. Increases in subcortical structures and cerebellum but not in nonvisual cortex. J. Cogn. Neurosci., 1997, 9(5), 624-647.
[] [PMID: 23965121]
Greicius, M.D.; Krasnow, B.; Reiss, A.L.; Menon, V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc. Natl. Acad. Sci. USA, 2003, 100(1), 253-258.
[] [PMID: 12506194]
Raichle, M.E.; MacLeod, A.M.; Snyder, A.Z.; Powers, W.J.; Gusnard, D.A.; Shulman, G.L. A default mode of brain function. Proc. Natl. Acad. Sci. USA, 2001, 98(2), 676-682.
[] [PMID: 11209064]
Zysset, S.; Huber, O.; Ferstl, E.; von Cramon, D.Y. The anterior frontomedian cortex and evaluative judgment: an fMRI study. Neuroimage, 2002, 15(4), 983-991.
[] [PMID: 11906238]
Buckner, R.L.; Snyder, A.Z.; Shannon, B.J.; LaRossa, G.; Sachs, R.; Fotenos, A.F.; Sheline, Y.I.; Klunk, W.E.; Mathis, C.A.; Morris, J.C.; Mintun, M.A. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J. Neurosci., 2005, 25(34), 7709-7717.
[] [PMID: 16120771]
Baliki, M.N.; Geha, P.Y.; Apkarian, A.V.; Chialvo, D.R. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J. Neurosci., 2008, 28(6), 1398-1403.
[] [PMID: 18256259]
Cauda, F.; Sacco, K.; Duca, S.; Cocito, D.; D’Agata, F.; Geminiani, G.C.; Canavero, S. Altered resting state in diabetic neuropathic pain. PLoS One, 2009, 4(2)e4542
[] [PMID: 19229326]
Napadow, V.; LaCount, L.; Park, K.; As-Sanie, S.; Clauw, D.J.; Harris, R.E. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum., 2010, 62(8), 2545-2555.
[] [PMID: 20506181]
Harris, R.E.; Napadow, V.; Huggins, J.P.; Pauer, L.; Kim, J.; Hampson, J.; Sundgren, P.C.; Foerster, B.; Petrou, M.; Schmidt-Wilcke, T.; Clauw, D.J. Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients. Anesthesiology, 2013, 119(6), 1453-1464.
[] [PMID: 24343290]
Apkarian, A.V.; Sosa, Y.; Krauss, B.R.; Thomas, P.S.; Fredrickson, B.E.; Levy, R.E.; Harden, R.N.; Chialvo, D.R. Chronic pain patients are impaired on an emotional decision-making task. Pain, 2004, 108(1-2), 129-136.
[] [PMID: 15109516]
Baliki, M.N.; Petre, B.; Torbey, S.; Herrmann, K.M.; Huang, L.; Schnitzer, T.J.; Fields, H.L.; Apkarian, A.V. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat. Neurosci., 2012, 15(8), 1117-1119.
[] [PMID: 22751038]
Hashmi, J.A.; Baliki, M.N.; Huang, L.; Baria, A.T.; Torbey, S.; Hermann, K.M.; Schnitzer, T.J.; Apkarian, A.V. Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain, 2013, 136(Pt 9), 2751-2768.
[] [PMID: 23983029]
Napadow, V.; Kim, J.; Clauw, D.J.; Harris, R.E. Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis Rheum., 2012, 64(7), 2398-2403.
[] [PMID: 22294427]
Riedl, V.; Valet, M.; Wöller, A.; Sorg, C.; Vogel, D.; Sprenger, T.; Boecker, H.; Wohlschläger, A.M.; Tölle, T.R. Repeated pain induces adaptations of intrinsic brain activity to reflect past and predict future pain. Neuroimage, 2011, 57(1), 206-213.
[] [PMID: 21514392]
Amir, R.; Kocsis, J.D.; Devor, M. Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons. J. Neurosci., 2005, 25(10), 2576-2585.
[] [PMID: 15758167]
Wu, G.; Ringkamp, M.; Murinson, B.B.; Pogatzki, E.M.; Hartke, T.V.; Weerahandi, H.M.; Campbell, J.N.; Griffin, J.W.; Meyer, R.A. Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J. Neurosci., 2002, 22(17), 7746-7753.
[] [PMID: 12196598]
Bostock, H.; Campero, M.; Serra, J.; Ochoa, J.L. Temperature-dependent double spikes in C-nociceptors of neuropathic pain patients. Brain, 2005, 128(Pt 9), 2154-2163.
[] [PMID: 15947060]
Lai, J.; Hunter, J.C.; Porreca, F. The role of voltage-gated sodium channels in neuropathic pain. Curr. Opin. Neurobiol., 2003, 13(3), 291-297.
[] [PMID: 12850213]
Hains, B.C.; Waxman, S.G. Sodium channel expression and the molecular pathophysiology of pain after SCI. Prog. Brain Res., 2007, 161, 195-203.
[] [PMID: 17618978]
Sheets, P.L.; Heers, C.; Stoehr, T.; Cummins, T.R. Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J. Pharmacol. Exp. Ther., 2008, 326(1), 89-99.
[] [PMID: 18378801]
Russo, R.; Caroleo, M.C.; Cione, E.; Perri, M.; Paparo, M.T.; Russo, A. Dual effect of ziconotide in primary erythromelalgia. Case Rep. Med., 2015, 2015592170
[] [PMID: 26609309]
Caroleo, M.C.; Cione, E. The challenging task of erythromelalgia therapy. J. Rep. Endo. Infert., 2017, 2, 19.
Drenth, J.P.; Waxman, S.G. Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J. Clin. Invest., 2007, 117(12), 3603-3609.
[] [PMID: 18060017]
Black, J.A.; Dib-Hajj, S.; McNabola, K.; Jeste, S.; Rizzo, M.A.; Kocsis, J.D.; Waxman, S.G. Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. Brain Res. Mol. Brain Res., 1996, 43(1-2), 117-131.
[] [PMID: 9037525]
Toledo-Aral, J.J.; Moss, B.L.; He, Z.J.; Koszowski, A.G.; Whisenand, T.; Levinson, S.R.; Wolf, J.J.; Silos-Santiago, I.; Halegoua, S.; Mandel, G. Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc. Natl. Acad. Sci. USA, 1997, 94(4), 1527-1532.
[] [PMID: 9037087]
Sangameswaran, L.; Fish, L.M.; Koch, B.D.; Rabert, D.K.; Delgado, S.G.; Ilnicka, M.; Jakeman, L.B.; Novakovic, S.; Wong, K.; Sze, P.; Tzoumaka, E.; Stewart, G.R.; Herman, R.C.; Chan, H.; Eglen, R.M.; Hunter, J.C. A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J. Biol. Chem., 1997, 272(23), 14805-14809.
[] [PMID: 9169448]
Djouhri, L.; Newton, R.; Levinson, S.R.; Berry, C.M.; Carruthers, B.; Lawson, S.N. Sensory and electrophysiological properties of guinea-pig sensory neurones expressing Nav 1.7 (PN1) Na+ channel alpha subunit protein. J. Physiol., 2003, 546(Pt 2), 565-576.
[] [PMID: 12527742]
Tang, Z.; Chen, Z.; Tang, B.; Jiang, H. Primary erythromelalgia: a review. Orphanet J. Rare Dis., 2015, 10, 127.
[] [PMID: 26419464]
Bahia, P.K.; Suzuki, R.; Benton, D.C.; Jowett, A.J.; Chen, M.X.; Trezise, D.J.; Dickenson, A.H.; Moss, G.W. A functional role for small-conductance calcium-activated potassium channels in sensory pathways including nociceptive processes. J. Neurosci., 2005, 25(14), 3489-3498.
[] [PMID: 15814779]
Norbury, T.A.; MacGregor, A.J.; Urwin, J.; Spector, T.D.; McMahon, S.B. Heritability of responses to painful stimuli in women: a classical twin study. Brain, 2007, 130(Pt 11), 3041-3049.
[] [PMID: 17932101]
Nielsen, C.S.; Stubhaug, A.; Price, D.D.; Vassend, O.; Czajkowski, N.; Harris, J.R. Individual differences in pain sensitivity: genetic and environmental contributions. Pain, 2008, 136(1-2), 21-29.
[] [PMID: 17692462]
Hartvigsen, J.; Nielsen, J.; Kyvik, K.O.; Fejer, R.; Vach, W.; Iachine, I.; Leboeuf-Yde, C. Heritability of spinal pain and consequences of spinal pain: a comprehensive genetic epidemiologic analysis using a population-based sample of 15,328 twins ages 20-71 years. Arthritis Rheum., 2009, 61(10), 1343-1351.
[] [PMID: 19790135]
Williams, F.M.; Scollen, S.; Cao, D.; Memari, Y.; Hyde, C.L.; Zhang, B.; Sidders, B.; Ziemek, D.; Shi, Y.; Harris, J.; Harrow, I.; Dougherty, B.; Malarstig, A.; McEwen, R.; Stephens, J.C.; Patel, K.; Menni, C.; Shin, S-Y.; Hodgkiss, D.; Surdulescu, G.; He, W.; Jin, X.; McMahon, S.B.; Soranzo, N.; John, S.; Wang, J.; Spector, T.D. Genes contributing to pain sensitivity in the normal population: an exome sequencing study. PLoS Genet., 2012, 8(12)e1003095
[] [PMID: 23284290]
Hocking, L.J.; Morris, A.D.; Dominiczak, A.F.; Porteous, D.J.; Smith, B.H. Generation Scotland. Heritability of chronic pain in 2195 extended families. Eur. J. Pain, 2012, 16(7), 1053-1063.
[] [PMID: 22337623]
Aiello, F.; Carullo, G.; Badolato, M.; Brizzi, A. TRPV1-FAAH-COX: The couples game in pain treatment. ChemMedChem, 2016, 11(16), 1686-1694.
[] [PMID: 27240888]
Ma, W.; Zhang, Y.; Bantel, C.; Eisenach, J.C. Medium and large injured dorsal root ganglion cells increase TRPV-1, accompanied by increased alpha2C-adrenoceptor co-expression and functional inhibition by clonidine. Pain, 2005, 113(3), 386-394.
[] [PMID: 15661448]
Ultenius, C.; Linderoth, B.; Meyerson, B.A.; Wallin, J. Spinal NMDA receptor phosphorylation correlates with the presence of neuropathic signs following peripheral nerve injury in the rat. Neurosci. Lett., 2006, 399(1-2), 85-90.
[] [PMID: 16469445]
Hains, B.C.; Saab, C.Y.; Klein, J.P.; Craner, M.J.; Waxman, S.G. Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J. Neurosci., 2004, 24(20), 4832-4839.
[] [PMID: 15152043]
Finnerup, N.B.; Jensen, T.S. Spinal cord injury pain--mechanisms and treatment. Eur. J. Neurol., 2004, 11(2), 73-82.
[] [PMID: 14748766]
Ducreux, D.; Attal, N.; Parker, F.; Bouhassira, D. Mechanisms of central neuropathic pain: a combined psychophysical and fMRI study in syringomyelia. Brain, 2006, 129(Pt 4), 963-976.
[] [PMID: 16434417]
Wasner, G.; Lee, B.B.; Engel, S.; McLachlan, E. Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. Brain, 2008, 131(Pt 9), 2387-2400.
[] [PMID: 18669485]
Scholz, J.; Woolf, C.J. The neuropathic pain triad: neurons, immune cells and glia. Nat. Neurosci., 2007, 10(11), 1361-1368.
[] [PMID: 17965656]
Saab, C.Y.; Waxman, S.G.; Hains, B.C. Alarm or curse? The pain of neuroinflammation. Brain Res. Brain Res. Rev., 2008, 58(1), 226-235.
[] [PMID: 18486228]
Milligan, E.D.; Watkins, L.R. Pathological and protective roles of glia in chronic pain. Nat. Rev. Neurosci., 2009, 10(1), 23-36.
[] [PMID: 19096368]
Nadeau, S.; Filali, M.; Zhang, J.; Kerr, B.J.; Rivest, S.; Soulet, D.; Iwakura, Y.; de Rivero Vaccari, J.P.; Keane, R.W.; Lacroix, S. Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1β and TNF: implications for neuropathic pain. J. Neurosci., 2011, 31(35), 12533-12542.
[] [PMID: 21880915]
Ma, C.; Shu, Y.; Zheng, Z.; Chen, Y.; Yao, H.; Greenquist, K.W.; White, F.A.; LaMotte, R.H. Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J. Neurophysiol., 2003, 89(3), 1588-1602.
[] [PMID: 12612024]
Murinson, B.B.; Archer, D.R.; Li, Y.; Griffin, J.W. Degeneration of myelinated efferent fibers prompts mitosis in Remak Schwann cells of uninjured C-fiber afferents. J. Neurosci., 2005, 25(5), 1179-1187.
[] [PMID: 15689554]
Bennett, D.L.; Koltzenburg, M.; Priestley, J.V.; Shelton, D.L.; McMahon, S.B. Endogenous nerve growth factor regulates the sensitivity of nociceptors in the adult rat. Eur. J. Neurosci., 1998, 10(4), 1282-1291.
[] [PMID: 9749782]
Sorkin, L.S.; Xiao, W.H.; Wagner, R.; Myers, R.R. Tumour necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neuroscience, 1997, 81(1), 255-262.
[] [PMID: 9300418]
Taiwo, Y.O.; Levine, J.D. Prostaglandin effects after elimination of indirect hyperalgesic mechanisms in the skin of the rat. Brain Res., 1989, 492(1-2), 397-399.
[] [PMID: 2665905]
Binshtok, A.M.; Wang, H.; Zimmermann, K.; Amaya, F.; Vardeh, D.; Shi, L.; Brenner, G.J.; Ji, R.R.; Bean, B.P.; Woolf, C.J.; Samad, T.A. Nociceptors are interleukin-1beta sensors. J. Neurosci., 2008, 28(52), 14062-14073.
[] [PMID: 19109489]
Woolf, C.J.; Ma, Q. Nociceptors--noxious stimulus detectors. Neuron, 2007, 55(3), 353-364.
[] [PMID: 17678850]
Kim, C.F.; Moalem-Taylor, G. Detailed characterization of neuro-immune responses following neuropathic injury in mice. Brain Res., 2011, 1405, 95-108.
[] [PMID: 21741621]
Morin, N.; Owolabi, S.A.; Harty, M.W.; Papa, E.F.; Tracy, T.F. Jr Shaw, S.K.; Kim, M.; Saab, C.Y. . Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve. J. Neuroimmunol., 2007, 184(1-2), 164-171.
[] [PMID: 17275921]
Hu, P.; Bembrick, A.L.; Keay, K.A.; McLachlan, E.M. Immune cell involvement in dorsal root ganglia and spinal cord after chronic constriction or transection of the rat sciatic nerve. Brain Behav. Immun., 2007, 21(5), 599-616.
[] [PMID: 17187959]
Hu, P.; McLachlan, E.M. Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience, 2002, 112(1), 23-38.
[] [PMID: 12044469]
Tanaka, T.; Minami, M.; Nakagawa, T.; Satoh, M. Enhanced production of monocyte chemoattractant protein-1 in the dorsal root ganglia in a rat model of neuropathic pain: possible involvement in the development of neuropathic pain. Neurosci. Res., 2004, 48(4), 463-469.
[] [PMID: 15041200]
Beggs, S.; Liu, X.J.; Kwan, C.; Salter, M.W. Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier. Mol. Pain, 2010, 6, 74.
[] [PMID: 21044346]
Echeverry, S.; Shi, X.Q.; Rivest, S.; Zhang, J. Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J. Neurosci., 2011, 31(30), 10819-10828.
[] [PMID: 21795534]
Kawasaki, Y.; Zhang, L.; Cheng, J.K.; Ji, R.R. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J. Neurosci., 2008, 28(20), 5189-5194.
[] [PMID: 18480275]
Molyva, D. Neuropeptides and pain. Ann. Gen. Psychiatry, 2010, 9(Suppl. 1), S3.
DeLeo, J.A.; Yezierski, R.P. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain, 2001, 90(1-2), 1-6.
[] [PMID: 11166964]
Seybold, V.S. The role of peptides in central sensitization. Handb. Exp. Pharmacol., 2009, 194(194), 451-491.
[] [PMID: 19655115]
Bouhassira, D.; Attal, N. Translational neuropathic pain research: A clinical perspective. Neuroscience, 2016, 338, 27-35.
[] [PMID: 26995083]
Schmidt-Wilcke, T.; Ichesco, E.; Hampson, J.P.; Kairys, A.; Peltier, S.; Harte, S.; Clauw, D.J.; Harris, R.E. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients. Neuroimage Clin., 2014, 6, 252-261.
[] [PMID: 25379438]
Letzen, J.E.; Craggs, J.G.; Perlstein, W.M.; Price, D.D.; Robinson, M.E. Functional connectivity of the default mode network and its association with pain networks in irritable bowel patients assessed via lidocaine treatment. J. Pain, 2013, 14(10), 1077-1087.
[] [PMID: 23743257]
Langley, P.C.; Van Litsenburg, C.; Cappelleri, J.C.; Carroll, D. The burden associated with neuropathic pain in Western Europe. J. Med. Econ., 2013, 16(1), 85-95.
[] [PMID: 22970839]
Widerström-Noga, E. Neuropathic pain and spinal cord injury: phenotypes and pharmacological management. Drugs, 2017, 77(9), 967-984.
[] [PMID: 28451808]
Finnerup, N.B.; Attal, N.; Haroutounian, S.; McNicol, E.; Baron, R.; Dworkin, R.H.; Gilron, I.; Haanpää, M.; Hansson, P.; Jensen, T.S.; Kamerman, P.R.; Lund, K.; Moore, A.; Raja, S.N.; Rice, A.S.C.; Rowbotham, M.; Sena, E.; Siddall, P.; Smith, B.H.; Wallace, M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol., 2015, 14(2), 162-173.
[] [PMID: 25575710]
Smith, M.D.; Woodhead, J.H.; Handy, L.J.; Pruess, T.H.; Vanegas, F.; Grussendorf, E.; Grussendorf, J.; White, K.; Bulaj, K.K.; Krumin, R.K.; Hunt, M.; Wilcox, K.S. Preclinical comparison of mechanistically different antiseizure, antinociceptive, and/or antidepressant drugs in a battery of rodent models of nociceptive and neuropathic pain. Neurochem. Res., 2017, 42(7), 1995-2010.
[] [PMID: 28508174]
Nishikawa, N.; Nomoto, M. Management of neuropathic pain. J Gen Fam Med, 2017, 18(2), 56-60.
[] [PMID: 29263992]
Hagen, E.M.; Rekand, T. Management of neuropathic pain associated with spinal cord injury. Pain Ther., 2015, 4(1), 51-65.
[] [PMID: 25744501]
Jensen, T.S.; Finnerup, N.B. Management of neuropathic pain. Curr. Opin. Support. Palliat. Care, 2007, 1(2), 126-131.
[] [PMID: 18685353]
Bannister, K.; Qu, C.; Navratilova, E.; Oyarzo, J.; Xie, J.Y.; King, T.; Dickenson, A.H.; Porreca, F. Multiple sites and actions of gabapentin-induced relief of ongoing experimental neuropathic pain. Pain, 2017, 158(12), 2386-2395.
[] [PMID: 28832395]
Chaudhry, M.; Alessandrini, M.; Rademan, J.; Dodgen, T.M.; Steffens, F.E.; van Zyl, D.G.; Gaedigk, A.; Pepper, M.S. Impact of CYP2D6 genotype on amitriptyline efficacy for the treatment of diabetic peripheral neuropathy: a pilot study. Pharmacogenomics, 2017, 18(5), 433-443.
[] [PMID: 28350251]
Roy, M.K.; Kuriakose, A.S.; Varma, S.K.; Jacob, L.A.; Beegum, N.J. A study on comparative efficacy and cost effectiveness of Pregabalin and Duloxetine used in diabetic neuropathic pain. Diabetes Metab. Syndr., 2017, 11(1), 31-35.
[] [PMID: 27484440]
Baloh, R.W. Treatment of chronic neuropathic pain in: Sciatica and Chronic Pain.; Baloh, R.W. (Ed.); Springer . , 2019, pp. 89-107.
Vinik, A.I.; Tuchman, M.; Safirstein, B.; Corder, C.; Kirby, L.; Wilks, K.; Quessy, S.; Blum, D.; Grainger, J.; White, J.; Silver, M. Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies. Pain, 2007, 128(1-2), 169-179.
[] [PMID: 17161535]
Paudel, K.R.; Bhattacharya, S.; Rauniar, G.; Das, B. Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats. J. Neurosci. Rural Pract., 2011, 2(2), 130-136.
[] [PMID: 21897674]
Faria, J.; Barbosa, J.; Moreira, R.; Queirós, O.; Carvalho, F.; Dinis-Oliveira, R.J. Comparative pharmacology and toxicology of tramadol and tapentadol. Eur. J. Pain, 2018, 22(5), 827-844.
[] [PMID: 29369473]
Rigo, F.K.; Trevisan, G.; Godoy, M.C.; Rossato, M.F.; Dalmolin, G.D.; Silva, M.A.; Menezes, M.S.; Caumo, W.; Ferreira, J. Management of neuropathic chronic pain with methadone combined with ketamine: a randomized, double blind, active-controlled clinical trial. Pain Physician, 2017, 20(3), 207-215.
[PMID: 28339433]
Safakhah, H.A.; Moradi Kor, N.; Bazargani, A.; Bandegi, A.R.; Gholami Pourbadie, H.; Khoshkholgh-Sima, B.; Ghanbari, A. Forced exercise attenuates neuropathic pain in chronic constriction injury of male rat: an investigation of oxidative stress and inflammation. J. Pain Res., 2017, 10, 1457-1466.
[] [PMID: 28721088]
Baron, R.; Allegri, M.; Correa-Illanes, G.; Hans, G.; Serpell, M.; Mick, G.; Mayoral, V. The 5% lidocaine-medicated plaster: its inclusion in international treatment guidelines for treating localized neuropathic pain, and clinical evidence supporting its use. Pain Ther., 2016, 5(2), 149-169.
[] [PMID: 27822619]
Russo, E.B. Cannabinoids in the management of difficult to treat pain. Ther. Clin. Risk Manag., 2008, 4(1), 245-259.
[] [PMID: 18728714]
Finnerup, N.B.; Haroutounian, S. Recommendations for Pharmacologic Therapy of Neuropathic Pain in: Essentials of Pain Medicine. Benzon, H.T.; Raja, S.N.; Fishman, S.M.; Liu, S.S; Cohen, S.P., Ed.; Elsevier, 2018, pp. 445-446.
Meng, H.; Johnston, B.; Englesakis, M.; Moulin, D.E.; Bhatia, A. Selective cannabinoids for chronic neuropathic pain: a systematic review and meta-analysis. Anesth. Analg., 2017, 125(5), 1638-1652.
[] [PMID: 28537982]
Markovits, E.; Gilhar, A. Capsaicin--an effective topical treatment in pain. Int. J. Dermatol., 1997, 36(6), 401-404.
[] [PMID: 9248881]
van Nooten, F.; Treur, M.; Pantiri, K.; Stoker, M.; Charokopou, M. Capsaicin 8% patch versus oral neuropathic pain medications for the treatment of painful diabetic peripheral neuropathy: A systematic literature review and network meta-analysis. Clin. Ther., 2017, 39(4), 787-803.e18.
[] [PMID: 28365034]
Zhao, S.; Yang, J.; Han, X.; Gong, Y.; Rao, S.; Wu, B.; Yi, Z.; Zou, L.; Jia, T.; Li, L.; Yuan, H.; Shi, L.; Zhang, C.; Gao, Y.; Li, G.; Liu, S.; Xu, H.; Liu, H.; Liang, S. Effects of nanoparticle-encapsulated curcumin on HIV-gp120-associated neuropathic pain induced by the P2X3 receptor in dorsal root ganglia. Brain Res. Bull., 2017, 135, 53-61.
[] [PMID: 28962965]
Verma, S.; Jain, C.P.; Chauhan, L.S.; Shukla, A.K. A review on treatment and management of neuropathic pain with herbal folk drugs. AJPP, 2016, 2, 104-110.
Petrosino, S.; Di Marzo, V. The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br. J. Pharmacol., 2017, 174(11), 1349-1365.
[] [PMID: 27539936]
Lo Verme, J.; Fu, J.; Astarita, G.; La Rana, G.; Russo, R.; Calignano, A.; Piomelli, D. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol. Pharmacol., 2005, 67(1), 15-19.
[] [PMID: 15465922]
Ryberg, E.; Larsson, N.; Sjögren, S.; Hjorth, S.; Hermansson, N.O.; Leonova, J.; Elebring, T.; Nilsson, K.; Drmota, T.; Greasley, P.J. The orphan receptor GPR55 is a novel cannabinoid receptor. Br. J. Pharmacol., 2007, 152(7), 1092-1101.
[] [PMID: 17876302]
Yoshihara, S.; Morimoto, H.; Ohori, M.; Yamada, Y.; Abe, T.; Arisaka, O. Cannabinoid receptor agonists inhibit Ca(2+) influx to synaptosomes from rat brain. Pharmacology, 2006, 76(4), 157-162.
[] [PMID: 16446560]
Aloe, L.; Leon, A.; Levi-Montalcini, R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions, 1993, 39(Spec No), C145-C147.
[] [PMID: 7505999]
Costa, B.; Comelli, F.; Bettoni, I.; Colleoni, M.; Giagnoni, G. The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain, 2008, 139(3), 541-550.
[] [PMID: 18602217]
Hesselink, J.M.K.; Hekker, T.A.M. Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J. Pain Res., 2012, 5, 437-442.
[] [PMID: 23166447]
Evangelista, M.; Cilli, V.; De Vitis, R.; Militerno, A.; Fanfani, F. Ultra-micronized palmitoylethanolamide effects on sleep-wake rhythm and neuropathic pain phenotypes in patients with carpal tunnel syndrome: an open-label, randomized controlled study. CNS Neurol. Disord. Drug Targets, 2018, 17(4), 291-298.
[] [PMID: 29676237]
Chirchiglia, D.; Cione, E.; Caroleo, M.C.; Wang, M.; Di Mizio, G.; Faedda, N.; Giacolini, T.; Siviglia, S.; Guidetti, V.; Gallelli, L. Effects of add-on ultramicronized N-Palmitol ethanol amide in patients suffering of migraine with aura: a pilot study. Front. Neurol., 2018, 9, 674.
[] [PMID: 30177906]
Chirchiglia, D.; Paventi, S.; Seminara, P.; Cione, E.; Gallelli, L. N-Palmitoyl ethanol amide pharmacological treatment in patients with nonsurgical lumbar radiculopathy. J. Clin. Pharmacol., 2018, 58(6), 733-739.
[] [PMID: 29364513]
Chaumette, T.; Chapuy, E.; Berrocoso, E.; Llorca-Torralba, M.; Bravo, L.; Mico, J.A.; Chalus, M.; Eschalier, A.; Ardid, D.; Marchand, F.; Sors, A. Effects of S 38093, an antagonist/inverse agonist of histamine H3 receptors, in models of neuropathic pain in rats. Eur. J. Pain, 2018, 22(1), 127-141.
[] [PMID: 28877402]
Abdel-Magid, A.F. Inhibitors of adaptor-associated kinase 1 (AAK1) may treat neuropathic pain, schizophrenia, parkinson’s disease, and other disorders. ACS Med. Chem. Lett., 2017, 8(6), 595-597.
[] [PMID: 28626516]
Supuran, C.T. Carbonic anhydrase inhibition and the management of neuropathic pain. Expert Rev. Neurother., 2016, 16(8), 961-968.
[] [PMID: 27211329]
Davis, M.P. Sigma-1 receptors and animal studies centered on pain and analgesia. Expert Opin. Drug Discov., 2015, 10(8), 885-900.
[] [PMID: 26037105]
Chien, C.C.; Pasternak, G.W. Functional antagonism of morphine analgesia by (+)-pentazocine: evidence for an anti-opioid σ 1 system. Eur. J. Pharmacol., 1993, 250(1), R7-R8.
[] [PMID: 8119306]
Chien, C.C.; Carroll, F.I.; Brown, G.P.; Pan, Y.X.; Bowen, W.; Pasternak, G.W. Synthesis and characterization of [125I]3′-(-)-iodopentazocine, a selective σ 1 receptor ligand. Eur. J. Pharmacol., 1997, 321(3), 361-368.
[] [PMID: 9085049]
Inoue, A.; Sugita, S.; Shoji, H.; Ichimoto, H.; Hide, I.; Nakata, Y. Repeated haloperidol treatment decreases sigma(1) receptor binding but does not affect its mRNA levels in the guinea pig or rat brain. Eur. J. Pharmacol., 2000, 401(3), 307-316.
[] [PMID: 10936488]
Vela, J.M.; Merlos, M.; Almansa, C. Investigational sigma-1 receptor antagonists for the treatment of pain. Expert Opin. Investig. Drugs, 2015, 24(7), 883-896.
[] [PMID: 26037209]
Cobos, E.J.; del Pozo, E.; Baeyens, J.M. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells. J. Neurochem., 2007, 102(3), 812-825.
[] [PMID: 17419803]
Entrena, J.M.; Cobos, E.J.; Nieto, F.R.; Cendán, C.M.; Baeyens, J.M.; Del Pozo, E. Antagonism by haloperidol and its metabolites of mechanical hypersensitivity induced by intraplantar capsaicin in mice: role of sigma-1 receptors. Psychopharmacology (Berl.), 2009, 205(1), 21-33.
[] [PMID: 19326101]
Salpeter, S.R.; Buckley, J.S.; Buckley, N.S.; Bruera, E. The use of very-low-dose methadone and haloperidol for pain control in the hospital setting: a preliminary report. J. Palliat. Med., 2015, 18(2), 114-119.
[] [PMID: 25494475]
Cobos, E.J.; Baeyens, J.M. Use of very-low-dose methadone and haloperidol for pain control in palliative care patients: are the sigma-1 receptors involved? J. Palliat. Med., 2015, 18(8), 660.
[] [PMID: 26087240]
Kim, F.J.; Kovalyshyn, I.; Burgman, M.; Neilan, C.; Chien, C.C.; Pasternak, G.W. Sigma 1 receptor modulation of G-protein-coupled receptor signaling: potentiation of opioid transduction independent from receptor binding. Mol. Pharmacol., 2010, 77(4), 695-703.
[] [PMID: 20089882]
Gris, G.; Portillo-Salido, E.; Aubel, B.; Darbaky, Y.; Deseure, K.; Vela, J.M.; Merlos, M.; Zamanillo, D. The selective sigma-1 receptor antagonist E-52862 attenuates neuropathic pain of different aetiology in rats. Sci. Rep., 2016, 6, 24591.
[] [PMID: 27087602]
Sahn, J.J.; Mejia, G.L.; Ray, P.R.; Martin, S.F.; Price, T.J. Sigma 2 receptor/Tmem97 agonists produce long lasting antineuropathic pain effects in mice. ACS Chem. Neurosci., 2017, 8(8), 1801-1811.
[] [PMID: 28644012]
Rais, R.; Vávra, J.; Tichý, T.; Dash, R.P.; Gadiano, A.J.; Tenora, L.; Monincová, L.; Bařinka, C.; Alt, J.; Zimmermann, S.C.; Slusher, C.E.; Wu, Y.; Wozniak, K.; Majer, P.; Tsukamoto, T.; Slusher, B.S. Discovery of a para-Acetoxy-benzyl ester prodrug of a hydroxamate-based glutamate carboxypeptidase ii inhibitor as oral therapy for neuropathic pain. J. Med. Chem., 2017, 60(18), 7799-7809.
[] [PMID: 28759215]
Liu, X.; Liu, H.; Dai, L.; Ma, B.; Ma, K. CXCR4 antagonist AMD3100 elicits analgesic effect and restores the GlyRα3 expression against neuropathic pain. J. Pain Res., 2017, 10, 2205-2212.
[] [PMID: 28919816]
Jung, Y.H.; Kim, Y.O.; Lin, H.; Cho, J.H.; Park, J.H.; Lee, S.D.; Bae, J.; Kang, K.M.; Kim, Y.G.; Pae, A.N.; Ko, H.; Park, C.S.; Yoon, M.H.; Kim, Y.C. Discovery of potent antiallodynic agents for neuropathic pain targeting P3X3 receptors. ACS Chem. Neurosci., 2017, 8(7), 1465-1478.
[] [PMID: 28323403]
Velasco, M.; O’Sullivan, C.; Sheridan, G.K. Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain. Neuropharmacology, 2017, 113(Pt B), 608-617.
U. S. National Library of Medicine Available at: . (Accessed Date: 25 January, 2018)
Weinstein, S.M.; Abernethy, A.P.; Spruill, S.E.; Pike, I.M.; True Kelly, A.; Jett, L.G. A spicamycin derivative (KRN5500) provides neuropathic pain relief in patients with advanced cancer: a placebo-controlled, proof-of-concept trial. J. Pain Symptom Manage., 2012, 43(4), 679-693.
[] [PMID: 21983265]
Gadgeel, S.M.; Boinpally, R.R.; Heilbrun, L.K.; Wozniak, A.; Jain, V.; Redman, B.; Zalupski, M.; Wiegand, R.; Parchment, R.; LoRusso, P.M. A phase I clinical trial of spicamycin derivative KRN5500 (NSC 650426) using a phase I accelerated titration “2B” design. Invest. New Drugs, 2003, 21(1), 63-74.
[] [PMID: 12795531]
Yamamoto, N.; Tamura, T.; Kamiya, Y.; Ono, H.; Kondoh, H.; Shirao, K.; Matsumura, Y.; Tanigawara, Y.; Shimada, Y. Phase I and pharmacokinetic study of KRN5500, a spicamycin derivative, for patients with advanced solid tumors. Jpn. J. Clin. Oncol., 2003, 33(6), 302-308.
[] [PMID: 12913085]
Andrew, R.; Derry, S.; Taylor, R.S.; Straube, S.; Phillips, C.J. The costs and consequences of adequately managed chronic non-cancer pain and chronic neuropathic pain. Pain Pract., 2014, 14(1), 79-94.
[] [PMID: 23464879]
Berger, A.; Dukes, E.M.; Oster, G. Clinical characteristics and economic costs of patients with painful neuropathic disorders. J. Pain, 2004, 5(3), 143-149.
[] [PMID: 15106126]
Dworkin, R.H.; O’Connor, A.B.; Backonja, M.; Farrar, J.T.; Finnerup, N.B.; Jensen, T.S.; Kalso, E.A.; Loeser, J.D.; Miaskowski, C.; Nurmikko, T.J.; Portenoy, R.K.; Rice, A.S.C.; Stacey, B.R.; Treede, R.D.; Turk, D.C.; Wallace, M.S. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain, 2007, 132(3), 237-251.
[] [PMID: 17920770]
Kremer, M.; Salvat, E.; Muller, A.; Yalcin, I.; Barrot, M. Antidepressants and gabapentinoids in neuropathic pain: Mechanistic insights. Neuroscience, 2016, 338, 183-206.
[] [PMID: 27401055]
Sałat, K.; Kowalczyk, P.; Gryzło, B.; Jakubowska, A.; Kulig, K. New investigational drugs for the treatment of neuropathic pain. Expert Opin. Investig. Drugs, 2014, 23(8), 1093-1104.
[] [PMID: 24896842]
V Euler, U.S; Gaddum, J.H. An unidentified depressor substance in certain tissue extracts. J. Physiol., 1931, 72(1), 74-87.
[] [PMID: 16994201]
Eipper, B.A.; Stoffers, D.A.; Mains, R.E. The biosynthesis of neuropeptides: peptide alpha-amidation. Annu. Rev. Neurosci., 1992, 15, 57-85.
[] [PMID: 1575450]
Marchand, J.E.; Hershman, K.; Kumar, M.S.; Thompson, M.L.; Kream, R.M. Disulfiram administration affects substance P-like immunoreactive and monoaminergic neural systems in rodent brain. J. Biol. Chem., 1990, 265(1), 264-273.
[PMID: 1688429]
Nawa, H.; Hirose, T.; Takashima, H.; Inayama, S.; Nakanishi, S. Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature, 1983, 306(5938), 32-36.
[] [PMID: 6195531]
Zubrzycka, M.; Janecka, A. Substance P: transmitter of nociception (Minireview). Endocr. Regul., 2000, 34(4), 195-201.
[PMID: 11137976]
Barnes, P.J. Asthma as an axon reflex. Lancet, 1986, 1(8475), 242-245.
[] [PMID: 2418322]
Lembeck, F.; Holzer, P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch. Pharmacol.,, 1979, 310(2), 175-183.
[] [PMID: 93706]
Levine, J.D.; Dardick, S.J.; Roizen, M.F.; Helms, C.; Basbaum, A.I. Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis. J. Neurosci., 1986, 6(12), 3423-3429.
[] [PMID: 3794780]
Mantyh, C.R.; Gates, T.S.; Zimmerman, R.P.; Welton, M.L.; Passaro, E.P., Jr; Vigna, S.R.; Maggio, J.E.; Kruger, L.; Mantyh, P.W. Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Proc. Natl. Acad. Sci. USA, 1988, 85(9), 3235-3239.
[] [PMID: 2834738]
Kramer, M.S.; Cutler, N.; Feighner, J.; Shrivastava, R.; Carman, J.; Sramek, J.J.; Reines, S.A.; Liu, G.; Snavely, D.; Wyatt-Knowles, E.; Hale, J.J.; Mills, S.G.; MacCoss, M.; Swain, C.J.; Harrison, T.; Hill, R.G.; Hefti, F.; Scolnick, E.M.; Cascieri, M.A.; Chicchi, G.G.; Sadowski, S.; Williams, A.R.; Hewson, L.; Smith, D.; Carlson, E.J.; Hargreaves, R.J.; Rupniak, N.M. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science, 1998, 281(5383), 1640-1645.
[] [PMID: 9733503]
De Araújo, J.E.; Huston, J.P.; Brandão, M.L. Opposite effects of substance P fragments C (anxiogenic) and N (anxiolytic) injected into dorsal periaqueductal gray. Eur. J. Pharmacol., 2001, 432(1), 43-51.
[] [PMID: 11734186]
Santarelli, L.; Gobbi, G.; Debs, P.C.; Sibille, E.T.; Blier, P.; Hen, R.; Heath, M.J. Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proc. Natl. Acad. Sci. USA, 2001, 98(4), 1912-1917.
[] [PMID: 11172050]
Persson, S.; Le Grevés, P.; Thörnwall, M.; Eriksson, U.; Silberring, J.; Nyberg, F. Neuropeptide converting and processing enzymes in the spinal cord and cerebrospinal fluid. Prog. Brain Res., 1995, 104, 111-130.
[] [PMID: 8552764]
Skidgel, R.A.; Engelbrecht, S.; Johnson, A.R.; Erdös, E.G. Hydrolysis of substance p and neurotensin by converting enzyme and neutral endopeptidase. Peptides, 1984, 5(4), 769-776.
[] [PMID: 6208535]
Yokosawa, H.; Endo, S.; Ogura, Y.; Ishii, S. A new feature of angiotensin-converting enzyme in the brain: hydrolysis of substance P. Biochem. Biophys. Res. Commun., 1983, 116(2), 735-742.
[] [PMID: 6197070]
Michael-Titus, A.T.; Fernandes, K.; Setty, H.; Whelpton, R. In vivo metabolism and clearance of substance P and co-expressed tachykinins in rat striatum. Neuroscience, 2002, 110(2), 277-286.
[] [PMID: 11958869]
Zhou, Q.; Liu, Z.; Ray, A.; Huang, W.; Karlsson, K.; Nyberg, F. Alteration in the brain content of substance P (1-7) during withdrawal in morphine-dependent rats. Neuropharmacology, 1998, 37(12), 1545-1552.
[] [PMID: 9886677]
Hallberg, M.; Nyberg, F. Neuropeptide conversion to bioactive fragments--an important pathway in neuromodulation. Curr. Protein Pept. Sci., 2003, 4(1), 31-44.
[] [PMID: 12570783]
Sakurada, T.; Le Grevés, P.; Stewart, J.; Terenius, L. Measurement of substance P metabolites in rat CNS. J. Neurochem., 1985, 44(3), 718-722.
[] [PMID: 2579196]
Wiktelius, D.; Khalil, Z.; Nyberg, F. Modulation of peripheral inflammation by the substance P N-terminal metabolite substance P1-7. Peptides, 2006, 27(6), 1490-1497.
[] [PMID: 16414148]
Tomaz, C.; Silva, A.C.; Nogueira, P.J. Long-lasting mnemotropic effect of substance P and its N-terminal fragment (SP1-7) on avoidance learning. Braz. J. Med. Biol. Res., 1997, 30(2), 231-233.
[] [PMID: 9239309]
Kreeger, J.S.; Larson, A.A. Substance P-(1-7), a substance P metabolite, inhibits withdrawal jumping in morphine-dependent mice. Eur. J. Pharmacol., 1993, 238(1), 111-115.
[] [PMID: 7691618]
Zhou, Q.; Frändberg, P.A.; Kindlundh, A.M.; Le Grevès, P.; Nyberg, F. Substance P(1-7) affects the expression of dopamine D2 receptor mRNA in male rat brain during morphine withdrawal. Peptides, 2003, 24(1), 147-153.
[] [PMID: 12576096]
Botros, M.; Hallberg, M.; Johansson, T.; Zhou, Q.; Lindeberg, G.; Frändberg, P.A.; Tömböly, C.; Tóth, G.; Le Grevès, P.; Nyberg, F. Endomorphin-1 and endomorphin-2 differentially interact with specific binding sites for substance P (SP) aminoterminal SP1-7 in the rat spinal cord. Peptides, 2006, 27(4), 753-759.
[] [PMID: 16216386]
Igwe, O.J.; Kim, D.C.; Seybold, V.S.; Larson, A.A. Specific binding of substance P aminoterminal heptapeptide [SP(1-7)] to mouse brain and spinal cord membranes. J. Neurosci., 1990, 10(11), 3653-3663.
[] [PMID: 1700082]
Botros, M.; Johansson, T.; Zhou, Q.; Lindeberg, G.; Tomboly, C.; Toth, G.; Le Greves, P.; Nyberg, F.; Hallberg, M. Endomorphins interact with the substance P (SP) aminoterminal SP1-7 binding in the ventral tegmental area of the rat brain. Peptides, 2008, 29, 1820-1824.
[] [PMID: 18597894]
Betancur, C.; Azzi, M.; Rostène, W. Nonpeptide antagonists of neuropeptide receptors: tools for research and therapy. Trends Pharmacol. Sci., 1997, 18(10), 372-386.
[] [PMID: 9357322]
Hökfelt, T.; Bartfai, T.; Bloom, F. Neuropeptides: opportunities for drug discovery. Lancet Neurol., 2003, 2(8), 463-472.
[] [PMID: 12878434]
Hökfelt, T.; Broberger, C.; Xu, Z.Q.D.; Sergeyev, V.; Ubink, R.; Diez, M. Neuropeptides--an overview. Neuropharmacology, 2000, 39(8), 1337-1356.
[] [PMID: 10818251]
Fransson, R.; Botros, M.; Nyberg, F.; Lindeberg, G.; Sandström, A.; Hallberg, M. Small peptides mimicking substance P (1-7) and encompassing a C-terminal amide functionality. Neuropeptides, 2008, 42(1), 31-37.
[] [PMID: 18093649]
Zadina, J.E.; Hackler, L.; Ge, L-J.; Kastin, A.J. A potent and selective endogenous agonist for the mu-opiate receptor. Nature, 1997, 386(6624), 499-502.
[] [PMID: 9087409]
Okada, Y.; Fujita, Y.; Motoyama, T.; Tsuda, Y.; Yokoi, T.; Li, T.; Sasaki, Y.; Ambo, A.; Jinsmaa, Y.; Bryant, S.D.; Lazarus, L.H. Structural studies of [2′,6′-dimethyl-L-tyrosine1]endomorphin-2 analogues: enhanced activity and cis orientation of the Dmt-Pro amide bond. Bioorg. Med. Chem., 2003, 11(9), 1983-1994.
[] [PMID: 12670649]
Kruszynski, R.; Fichna, J.; do-Rego, J-C.; Janecki, T.; Kosson, P.; Pakulska, W.; Costentin, J.; Janecka, A. Synthesis and biological activity of N-methylated analogs of endomorphin-2. Bioorg. Med. Chem., 2005, 13(24), 6713-6717.
[] [PMID: 16143536]
Fichna, J.; Janecka, A.; Costentin, J.; Do Rego, J-C. The endomorphin system and its evolving neurophysiological role. Pharmacol. Rev., 2007, 59(1), 88-123.
[] [PMID: 17329549]
Fransson, R.; Botros, M.; Sköld, C.; Nyberg, F.; Lindeberg, G.; Hallberg, M.; Sandström, A. Discovery of dipeptides with high affinity to the specific binding site for substance P1-7. J. Med. Chem., 2010, 53(6), 2383-2389.
[] [PMID: 20178322]
Ohsawa, M.; Carlsson, A.; Asato, M.; Koizumi, T.; Nakanishi, Y.; Fransson, R.; Sandström, A.; Hallberg, M.; Nyberg, F.; Kamei, J. The dipeptide Phe-Phe amide attenuates signs of hyperalgesia, allodynia and nociception in diabetic mice using a mechanism involving the sigma receptor system. Mol. Pain, 2011, 7, 85-95.
[] [PMID: 22040520]
Fransson, R.; Sköld, C.; Kratz, J.M.; Svensson, R.; Artursson, P.; Nyberg, F.; Hallberg, M.; Sandström, A. Constrained H-Phe-Phe-NH2 analogues with high affinity to the substance P1-7 binding site and with improved metabolic stability and cell permeability. J. Med. Chem., 2013, 56, 4953-4965.
[] [PMID: 23735006]
Thornber, C.W. Isosterism and molecular modification in drug design. Chem. Soc. Rev., 1979, 8, 563-580.
Chen, X.; Wang, W. The use of bioisosteric groups in lead optimization. Annu. Rep. Med. Chem., 2003, 38, 333-346.
Jonsson, A.; Fransson, R.; Haramaki, Skogh. A Brolin, E.; Watanabe, H.; Nordvall, G.; Hallberg, M.; Sandström, A; Nyberg, F.. Small Constrained SP1-7 analogs bind to a unique site and promote anti-allodynic effects following systemic injection in mice. Neurosci., 2015, 298, 112-119.
Carlsson-Jonsson, A.; Gao, T.; Hao, J-X.; Fransson, R.; Sandström, A.; Nyberg, F.; Wiesenfeld-Hallin, Z.; Xu, X-J. N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanic allodynia in rats. Eur. J. Pharm., 2014, 738, 319-325.
[] [PMID: 24933646]
Fransson, R.; Nordvall, G.; Bylund, J.; Carlsson-Jonsson, A.; Kratz, J.M.; Svensson, R.; Artursson, P.; Hallberg, M.; Sandström, A. Exploration and pharmacokinetic profiling of phenylalanine based carbamates as novel substance p 1-7 analogues. ACS Med. Chem. Lett., 2014, 5(12), 1272-1277.
[] [PMID: 25516784]
Skogh, A.; Lesniak, A.; Gaugaz, F.Z.; Svensson, R.; Lindeberg, G.; Fransson, R.; Nyberg, F.; Hallberg, M.; Sandström, A. Importance of N- and C-terminal residues of substance P 1-7 for alleviating allodynia in mice after peripheral administration. Eur. J. Pharm. Sci., 2017, 106, 345-351.
[] [PMID: 28587787]
Hallberg, M. Neuropeptides: metabolism to bioactive fragments and the pharmacology of their receptors. Med. Res. Rev., 2015, 35(3), 464-519.
[] [PMID: 24894913]
Brasnjevic, I.; Steinbusch, H.W.M.; Schmitz, C.; Martinez-Martinez, P. European NanoBioPharmaceutics Research Initiative. Delivery of peptide and protein drugs over the blood-brain barrier. Prog. Neurobiol., 2009, 87(4), 212-251.
[] [PMID: 19395337]
Chatterjee, J.; Rechenmacher, F.; Kessler, H. N-methylation of peptides and proteins: an important element for modulating biological functions. Angew. Chem. Int. Ed. Engl., 2013, 52(1), 254-269.
[] [PMID: 23161799]
Hill, T.A.; Shepherd, N.E.; Diness, F.; Fairlie, D.P. Constraining cyclic peptides to mimic protein structure motifs. Angew. Chem. Int. Ed. Engl., 2014, 53(48), 13020-13041.
[] [PMID: 25287434]
Pailleux, F.; Lemoine, J.; Beaudry, F. Investigation of the metabolic biotransformation of substance P in liver microsomes by liquid chromatography quadrupole ion trap mass spectrometry. Biomed. Chromatogr., 2013, 27(1), 39-47.
[] [PMID: 22544680]
Bose, P.P.; Chatterjee, U.; Hubatsch, I.; Artursson, P.; Govender, T.; Kruger, H.G.; Bergh, M.; Johansson, J.; Arvidsson, P.I. In vitro ADMET and physicochemical investigations of poly-N-methylated peptides designed to inhibit Abeta aggregation. Bioorg. Med. Chem., 2010, 18(16), 5896-5902.
[] [PMID: 20659803]
Ovadia, O.; Greenberg, S.; Laufer, B.; Gilon, C.; Hoffman, A.; Kessler, H. Improvement of drug-like properties of peptides: the somatostatin paradigm. Expert Opin. Drug Discov., 2010, 5(7), 655-671.
[] [PMID: 22823205]
Hemington, K.S.; Rogachov, A.; Cheng, J.C.; Bosma, R.L.; Kim, J.A.; Osborne, N.R.; Inman, R.D.; Davis, K.D. Patients with chronic pain exhibit a complex relationship triad between pain, resilience, and within- and cross-network functional connectivity of the default mode network. Pain, 2018, 159(8), 1621-1630.
[] [PMID: 29697536]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy