Top

Molecular Pain

Published in:

Open Access 01-12-2013 | Research

Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse

Authors: Noboru Iwagaki, Francesca Garzillo, Erika Polgár, John S Riddell, Andrew J Todd

Published in: Molecular Pain | Issue 1/2013

Abstract

Background

Inhibitory interneurons in the superficial dorsal horn play important roles in modulating sensory transmission, and these roles are thought to be performed by distinct functional populations. We have identified 4 non-overlapping classes among the inhibitory interneurons in the rat, defined by the presence of galanin, neuropeptide Y, neuronal nitric oxide synthase (nNOS) and parvalbumin. The somatostatin receptor sst_2A is expressed by ~50% of the inhibitory interneurons in this region, and is particularly associated with nNOS- and galanin-expressing cells. The main aim of the present study was to test whether a genetically-defined population of inhibitory interneurons, those expressing green fluorescent protein (GFP) in the PrP-GFP mouse, belonged to one or more of the neurochemical classes identified in the rat.

Results

The expression of sst_2A and its relation to other neurochemical markers in the mouse was similar to that in the rat, except that a significant number of cells co-expressed nNOS and galanin. The PrP-GFP cells were entirely contained within the set of inhibitory interneurons that possessed sst_2A receptors, and virtually all expressed nNOS and/or galanin. GFP was present in ~3-4% of neurons in the superficial dorsal horn, corresponding to ~16% of the inhibitory interneurons in this region. Consistent with their sst_2A-immunoreactivity, all of the GFP cells were hyperpolarised by somatostatin, and this was prevented by administration of a selective sst₂ receptor antagonist or a blocker of G-protein-coupled inwardly rectifying K⁺ channels.

Conclusions

These findings support the view that neurochemistry provides a valuable way of classifying inhibitory interneurons in the superficial laminae. Together with previous evidence that the PrP-GFP cells form a relatively homogeneous population in terms of their physiological properties, they suggest that these neurons have specific roles in processing sensory information in the dorsal horn.

Available only for authorised users

Todd AJ: Neuronal circuitry for pain processing in the dorsal horn. Nat Rev Neurosci 2010, 11: 823–836.PubMedCentralCrossRefPubMed

Polgár E, Hughes DI, Riddell JS, Maxwell DJ, Puskar Z, Todd AJ: Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain. Pain 2003, 104: 229–239. 10.1016/S0304-3959(03)00011-3CrossRefPubMed

Todd AJ, Sullivan AC: Light microscope study of the coexistence of GABA-like and glycine-like immunoreactivities in the spinal cord of the rat. J Comp Neurol 1990, 296: 496–505. 10.1002/cne.902960312CrossRefPubMed

Polgár E, Durrieux C, Hughes DI, Todd AJ: A quantitative study of inhibitory interneurons in laminae I-III of the mouse spinal dorsal horn. PloS one 2013, e78309.

Basbaum AI, Bautista DM, Scherrer G, Julius D: Cellular and molecular mechanisms of pain. Cell 2009, 139: 267–284. 10.1016/j.cell.2009.09.028PubMedCentralCrossRefPubMed

Ross SE, Mardinly AR, McCord AE, Zurawski J, Cohen S, Jung C, Hu L, Mok SI, Shah A, Savner EM, et al.: Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 2010, 65: 886–898. 10.1016/j.neuron.2010.02.025PubMedCentralCrossRefPubMed

Sandkuhler J: Models and mechanisms of hyperalgesia and allodynia. Physiol Rev 2009, 89: 707–758. 10.1152/physrev.00025.2008CrossRefPubMed

Zeilhofer HU, Wildner H, Yevenes GE: Fast synaptic inhibition in spinal sensory processing and pain control. Physiol Rev 2012, 92: 193–235. 10.1152/physrev.00043.2010PubMedCentralCrossRefPubMed

Gobel S: Golgi studies of the neurons in layer II of the dorsal horn of the medulla (trigeminal nucleus caudalis). J Comp Neurol 1978, 180: 395–413. 10.1002/cne.901800213CrossRefPubMed

10.

Graham BA, Brichta AM, Callister RJ: Moving from an averaged to specific view of spinal cord pain processing circuits. J Neurophysiol 2007, 98: 1057–1063. 10.1152/jn.00581.2007CrossRefPubMed

11.

Grudt TJ, Perl ER: Correlations between neuronal morphology and electrophysiological features in the rodent superficial dorsal horn. J Physiol 2002, 540: 189–207. 10.1113/jphysiol.2001.012890PubMedCentralCrossRefPubMed

12.

Heinke B, Ruscheweyh R, Forsthuber L, Wunderbaldinger G, Sandkuhler J: Physiological, neurochemical and morphological properties of a subgroup of GABAergic spinal lamina II neurones identified by expression of green fluorescent protein in mice. J Physiol 2004, 560: 249–266. 10.1113/jphysiol.2004.070540PubMedCentralCrossRefPubMed

13.

Polgár E, Sardella TCP, Tiong SYX, Locke S, Watanabe M, Todd AJ: Functional differences between neurochemically-defined populations of inhibitory interneurons in the rat spinal cord. Pain 2013, 2606–2615. in press

14.

Yasaka T, Tiong SYX, Hughes DI, Riddell JS, Todd AJ: Populations of inhibitory and excitatory interneurons in lamina II of the adult rat spinal dorsal horn revealed by a combined electrophysiological and anatomical approach. Pain 2010, 151: 475–488. 10.1016/j.pain.2010.08.008PubMedCentralCrossRefPubMed

15.

Maxwell DJ, Belle MD, Cheunsuang O, Stewart A, Morris R: Morphology of inhibitory and excitatory interneurons in superficial laminae of the rat dorsal horn. J Physiol 2007, 584: 521–533. 10.1113/jphysiol.2007.140996PubMedCentralCrossRefPubMed

16.

Davies AJ, North RA: Electrophysiological and morphological properties of neurons in the substantia gelatinosa of the mouse trigeminal subnucleus caudalis. Pain 2009, 146: 214–221. 10.1016/j.pain.2009.07.038CrossRefPubMed

17.

Laing I, Todd AJ, Heizmann CW, Schmidt HH: Subpopulations of GABAergic neurons in laminae I-III of rat spinal dorsal horn defined by coexistence with classical transmitters, peptides, nitric oxide synthase or parvalbumin. Neuroscience 1994, 61: 123–132. 10.1016/0306-4522(94)90065-5CrossRefPubMed

18.

Light AR, Trevino DL, Perl ER: Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn. J Comp Neurol 1979, 186: 151–171. 10.1002/cne.901860204CrossRefPubMed

19.

Lu Y, Perl ER: A specific inhibitory pathway between substantia gelatinosa neurons receiving direct C-fiber input. J Neurosci 2003, 23: 8752–8758.PubMed

20.

Lu Y, Perl ER: Modular organization of excitatory circuits between neurons of the spinal superficial dorsal horn (laminae I and II). J Neurosci 2005, 25: 3900–3907. 10.1523/JNEUROSCI.0102-05.2005CrossRefPubMed

21.

Réthelyi M, Light AR, Perl ER: Synaptic ultrastructure of functionally and morphologically characterized neurons of the superficial spinal dorsal horn of cat. J Neurosci 1989, 9: 1846–1863.PubMed

22.

Santos SF, Rebelo S, Derkach VA, Safronov BV: Excitatory interneurons dominate sensory processing in the spinal substantia gelatinosa of rat. J Physiol 2007, 581: 241–254. 10.1113/jphysiol.2006.126912PubMedCentralCrossRefPubMed

23.

Todd AJ, Lewis SG: The morphology of Golgi-stained neurons in lamina II of the rat spinal cord. J Anat 1986, 149: 113–119.PubMedCentralPubMed

24.

Wang H, Zylka MJ: Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons. J Neurosci 2009, 29: 13202–13209. 10.1523/JNEUROSCI.3248-09.2009PubMedCentralCrossRefPubMed

25.

Woolf CJ, Fitzgerald M: The properties of neurones recorded in the superficial dorsal horn of the rat spinal cord. J Comp Neurol 1983, 221: 313–328. 10.1002/cne.902210307CrossRefPubMed

26.

Hu HJ, Gereau RW: ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. II. Modulation of neuronal excitability. J Neurophysiol 2003, 90: 1680–1688. 10.1152/jn.00341.2003CrossRefPubMed

27.

Brohl D, Strehle M, Wende H, Hori K, Bormuth I, Nave KA, Muller T, Birchmeier C: A transcriptional network coordinately determines transmitter and peptidergic fate in the dorsal spinal cord. Dev Biol 2008, 322: 381–393. 10.1016/j.ydbio.2008.08.002CrossRefPubMed

28.

Wildner H, Das Gupta R, Brohl D, Heppenstall PA, Zeilhofer HU, Birchmeier C: Genome-wide expression analysis of Ptf1a- and Ascl1-deficient mice reveals new markers for distinct dorsal horn interneuron populations contributing to nociceptive reflex plasticity. J Neurosci 2013, 33: 7299–7307. 10.1523/JNEUROSCI.0491-13.2013PubMedCentralCrossRefPubMed

29.

Todd AJ, McKenzie J: GABA-immunoreactive neurons in the dorsal horn of the rat spinal cord. Neuroscience 1989, 31: 799–806. 10.1016/0306-4522(89)90442-9CrossRefPubMed

30.

Yasaka T, Kato G, Furue H, Rashid MH, Sonohata M, Tamae A, Murata Y, Masuko S, Yoshimura M: Cell-type-specific excitatory and inhibitory circuits involving primary afferents in the substantia gelatinosa of the rat spinal dorsal horn in vitro. J Physiol 2007, 581: 603–618. 10.1113/jphysiol.2006.123919PubMedCentralCrossRefPubMed

31.

Tiong SYX, Polgár E, van Kralingen JC, Watanabe M, Todd AJ: Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord. Mol Pain 2011, 7: 36. 10.1186/1744-8069-7-36PubMedCentralCrossRefPubMed

32.

Todd AJ, Spike RC, Polgar E: A quantitative study of neurons which express neurokinin-1 or somatostatin sst2a receptor in rat spinal dorsal horn. Neuroscience 1998, 85: 459–473. 10.1016/S0306-4522(97)00669-6CrossRefPubMed

33.

Daniele CA, MacDermott AB: Low-threshold primary afferent drive onto GABAergic interneurons in the superficial dorsal horn of the mouse. J Neurosci 2009, 29: 686–695. 10.1523/JNEUROSCI.5120-08.2009PubMedCentralCrossRefPubMed

34.

Hantman AW, Perl ER: Molecular and genetic features of a labeled class of spinal substantia gelatinosa neurons in a transgenic mouse. J Comp Neurol 2005, 492: 90–100. 10.1002/cne.20709CrossRefPubMed

35.

Hantman AW, van den Pol AN, Perl ER: Morphological and physiological features of a set of spinal substantia gelatinosa neurons defined by green fluorescent protein expression. J Neurosci 2004, 24: 836–842. 10.1523/JNEUROSCI.4221-03.2004CrossRefPubMed

36.

Hughes DI, Sikander S, Kinnon CM, Boyle KA, Watanabe M, Callister RJ, Graham BA: Morphological, neurochemical and electrophysiological features of parvalbumin-expressing cells: a likely source of axo-axonic inputs in the mouse spinal dorsal horn. J Physiol 2012, 590: 3927–3951. 10.1113/jphysiol.2012.235655PubMedCentralCrossRefPubMed

37.

Leitner J, Westerholz S, Heinke B, Forsthuber L, Wunderbaldinger G, Jager T, Gruber-Schoffnegger D, Braun K, Sandkuhler J: Impaired excitatory drive to spinal GABAergic neurons of neuropathic mice. PloS one 2013, 8: e73370. 10.1371/journal.pone.0073370PubMedCentralCrossRefPubMed

38.

Mesnage B, Gaillard S, Godin AG, Rodeau JL, Hammer M, Von Engelhardt J, Wiseman PW, De Koninck Y, Schlichter R, Cordero-Erausquin M: Morphological and functional characterization of cholinergic interneurons in the dorsal horn of the mouse spinal cord. J Comp Neurol 2011, 519: 3139–3158. 10.1002/cne.22668CrossRefPubMed

39.

Zeilhofer HU, Studler B, Arabadzisz D, Schweizer C, Ahmadi S, Layh B, Bosl MR, Fritschy JM: Glycinergic neurons expressing enhanced green fluorescent protein in bacterial artificial chromosome transgenic mice. J Comp Neurol 2005, 482: 123–141. 10.1002/cne.20349CrossRefPubMed

40.

Zheng J, Lu Y, Perl ER: Inhibitory neurones of the spinal substantia gelatinosa mediate interaction of signals from primary afferents. J Physiol 2010, 588: 2065–2075. 10.1113/jphysiol.2010.188052PubMedCentralCrossRefPubMed

41.

van den Pol AN, Ghosh PK, Liu RJ, Li Y, Aghajanian GK, Gao XB: Hypocretin (orexin) enhances neuron activity and cell synchrony in developing mouse GFP-expressing locus coeruleus. J Physiol 2002, 541: 169–185. 10.1113/jphysiol.2002.017426PubMedCentralCrossRefPubMed

42.

Kim SJ, Chung WH, Rhim H, Eun SY, Jung SJ, Kim J: Postsynaptic action mechanism of somatostatin on the membrane excitability in spinal substantia gelatinosa neurons of juvenile rats. Neuroscience 2002, 114: 1139–1148. 10.1016/S0306-4522(02)00245-2CrossRefPubMed

43.

Ottersen OP, Storm-Mathiesen J: Localization of amino acid neurotransmitters by immunocytochemistry. Trends Neurosci 1987, 10: 250–255. 10.1016/0166-2236(87)90168-8CrossRef

44.

Somogyi P, Hodgson AJ, Chubb IW, Penke B, Erdei A: Antisera to gamma-aminobutyric acid. II. Immunocytochemical application to the central nervous system. J Histochem Cytochem 1985, 33: 240–248. 10.1177/33.3.2579123CrossRefPubMed

45.

Sardella TC, Polgar E, Watanabe M, Todd AJ: A quantitative study of neuronal nitric oxide synthase expression in laminae I-III of the rat spinal dorsal horn. Neuroscience 2011, 192: 708–720.PubMedCentralCrossRefPubMed

46.

Sloviter RS, Ali-Akbarian L, Horvath KD, Menkens KA: Substance P receptor expression by inhibitory interneurons of the rat hippocampus: enhanced detection using improved immunocytochemical methods for the preservation and colocalization of GABA and other neuronal markers. J Comp Neurol 2001, 430: 283–305. 10.1002/1096-9861(20010212)430:3<283::AID-CNE1031>3.0.CO;2-VCrossRefPubMed

47.

Polgár E, Sardella T, Watanabe M, Todd AJ: A quantitative study of NPY-expressing GABAergic neurons and axons in rat spinal dorsal horn. J Comp Neurol 2011, 519: 1007–1023. 10.1002/cne.22570PubMedCentralCrossRefPubMed

48.

Pow DV, Crook DK: Extremely high titre polyclonal antisera against small neurotransmitter molecules: rapid production, characterisation and use in light- and electron-microscopic immunocytochemistry. J Neurosci Methods 1993, 48: 51–63. 10.1016/S0165-0270(05)80007-XCrossRefPubMed

49.

Herbison AE, Simonian SX, Norris PJ, Emson PC: Relationship of neuronal nitric oxide synthase immunoreactivity to GnRH neurons in the ovariectomized and intact female rat. J Neuroendocrinol 1996, 8: 73–82. 10.1111/j.1365-2826.1996.tb00688.xCrossRefPubMed

50.

Rowan S, Todd AJ, Spike RC: Evidence that neuropeptide Y is present in GABAergic neurons in the superficial dorsal horn of the rat spinal cord. Neuroscience 1993, 53: 537–545. 10.1016/0306-4522(93)90218-5CrossRefPubMed

51.

Simmons DR, Spike RC, Todd AJ: Galanin is contained in GABAergic neurons in the rat spinal dorsal horn. Neurosci Lett 1995, 187: 119–122. 10.1016/0304-3940(95)11358-4CrossRefPubMed

52.

Makwana M, Werner A, Acosta-Saltos A, Gonitel R, Pararajasingham A, Ruff C, Rumajogee P, Cuthill D, Galiano M, Bohatschek M, et al.: Peripheral facial nerve axotomy in mice causes sprouting of motor axons into perineuronal central white matter: time course and molecular characterization. J Comp Neurol 2010, 518: 699–721. 10.1002/cne.22240PubMedCentralCrossRefPubMed

53.

Mullen RJ, Buck CR, Smith AM: NeuN, a neuronal specific nuclear protein in vertebrates. Development 1992, 116: 201–211.PubMed

54.

Ruscheweyh R, Sandkuhler J: Lamina-specific membrane and discharge properties of rat spinal dorsal horn neurones in vitro. J Physiol 2002, 541: 231–244. 10.1113/jphysiol.2002.017756PubMedCentralCrossRefPubMed

55.

Jiang N, Furue H, Katafuchi T, Yoshimura M: Somatostatin directly inhibits substantia gelatinosa neurons in adult rat spinal dorsal horn in vitro. Neurosci Res 2003, 47: 97–107. 10.1016/S0168-0102(03)00183-4CrossRefPubMed

56.

Nakatsuka T, Fujita T, Inoue K, Kumamoto E: Activation of GIRK channels in substantia gelatinosa neurones of the adult rat spinal cord: a possible involvement of somatostatin. J Physiol 2008, 586: 2511–2522. 10.1113/jphysiol.2007.146076PubMedCentralCrossRefPubMed

57.

Polgar E, Sardella TC, Watanabe M, Todd AJ: Quantitative study of NPY-expressing GABAergic neurons and axons in rat spinal dorsal horn. J Comp Neurol 2011, 519: 1007–1023. 10.1002/cne.22570PubMedCentralCrossRefPubMed

58.

Polgár E, Shehab SA, Watt C, Todd AJ: GABAergic neurons that contain neuropeptide Y selectively target cells with the neurokinin 1 receptor in laminae III and IV of the rat spinal cord. J Neurosci 1999, 19: 2637–2646.PubMed

59.

Puskár Z, Polgár E, Todd AJ: A population of large lamina I projection neurons with selective inhibitory input in rat spinal cord. Neuroscience 2001, 102: 167–176. 10.1016/S0306-4522(00)00445-0CrossRefPubMed

60.

Antal M, Freund TF, Polgar E: Calcium-binding proteins, parvalbumin- and calbindin-D 28 k-immunoreactive neurons in the rat spinal cord and dorsal root ganglia: a light and electron microscopic study. J Comp Neurol 1990, 295: 467–484. 10.1002/cne.902950310CrossRefPubMed

61.

Spike RC, Todd AJ, Johnston HM: Coexistence of NADPH diaphorase with GABA, glycine, and acetylcholine in rat spinal cord. J Comp Neurol 1993, 335: 320–333. 10.1002/cne.903350303CrossRefPubMed

62.

Liuzzi FJ, Wu W, Scoville SA, Schinco FP: Development of nitric oxide synthase expression in the superficial dorsal horn of the rat spinal cord. Exp Neurol 1993, 121: 275–278. 10.1006/exnr.1993.1096CrossRefPubMed

63.

Kemp T, Spike RC, Watt C, Todd AJ: The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord. Neuroscience 1996, 75: 1231–1238. 10.1016/0306-4522(96)00333-8CrossRefPubMed

64.

Jeftinija S: Enkephalins modulate excitatory synaptic transmission in the superficial dorsal horn by acting at mu-opioid receptor sites. Brain research 1988, 460: 260–268. 10.1016/0006-8993(88)90371-XCrossRefPubMed

65.

Yoshimura M, North RA: Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 1983, 305: 529–530. 10.1038/305529a0CrossRefPubMed

66.

Schneider SP, Eckert WA 3rd, Light AR: Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell recordings in substantia gelatinosa neurons. J Neurophysiol 1998, 80: 2954–2962.PubMed

67.

Grudt TJ, Williams JT: mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat. J Neurosci 1994, 14: 1646–1654.PubMed

68.

Imhof AK, Gluck L, Gajda M, Lupp A, Brauer R, Schaible HG, Schulz S: Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis. Arthritis Rheum 2011, 63: 2352–2362. 10.1002/art.30410CrossRefPubMed

69.

Schulz S, Schreff M, Schmidt H, Handel M, Przewlocki R, Hollt V: Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia. Eur J Neurosci 1998, 10: 3700–3708. 10.1046/j.1460-9568.1998.00386.xCrossRefPubMed

70.

Schindler M, Sellers LA, Humphrey PP, Emson PC: Immunohistochemical localization of the somatostatin SST2(A) receptor in the rat brain and spinal cord. Neuroscience 1997, 76: 225–240.CrossRefPubMed

71.

Seybold VS, Hylden JL, Wilcox GL: Intrathecal substance P and somatostatin in rats: behaviors indicative of sensation. Peptides 1982, 3: 49–54. 10.1016/0196-9781(82)90141-3CrossRefPubMed

72.

Wiesenfeld-Hallin Z: Intrathecal somatostatin modulates spinal sensory and reflex mechanisms: behavioral and electrophysiological studies in the rat. Neurosci Lett 1985, 62: 69–74. 10.1016/0304-3940(85)90286-1CrossRefPubMed

73.

Wiesenfeld-Hallin Z: Somatostatin and calcitonin gene-related peptide synergistically modulate spinal sensory and reflex mechanisms in the rat: behavioral and electrophysiological studies. Neurosci Lett 1986, 67: 319–323. 10.1016/0304-3940(86)90329-0CrossRefPubMed

74.

Chapman V, Dickenson AH: The effects of sandostatin and somatostatin on nociceptive transmission in the dorsal horn of the rat spinal cord. Neuropeptides 1992, 23: 147–152. 10.1016/0143-4179(92)90115-DCrossRefPubMed

75.

Gaumann DM, Yaksh TL: Intrathecal somatostatin in rats: antinociception only in the presence of toxic effects. Anesthesiology 1988, 68: 733–742. 10.1097/00000542-198805000-00011CrossRefPubMed

76.

Mollenholt P, Post C, Rawal N, Freedman J, Hokfelt T, Paulsson I: Antinociceptive and 'neurotoxic' actions of somatostatin in rat spinal cord after intrathecal administration. Pain 1988, 32: 95–105. 10.1016/0304-3959(88)90028-0CrossRefPubMed

77.

Hokfelt T, Elde R, Johansson O, Luft R, Arimura A: Immunohistochemical evidence for presence of somatostatin, a powerful inhibitory peptide, in some primary sensory neurons. Neurosci Lett 1975, 1: 231–235. 10.1016/0304-3940(75)90066-XCrossRef

78.

Proudlock F, Spike RC, Todd AJ: Immunocytochemical study of somatostatin, neurotensin, GABA, and glycine in rat spinal dorsal horn. J Comp Neurol 1993, 327: 289–297. 10.1002/cne.903270210CrossRefPubMed

Title: Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse
Authors: Noboru Iwagaki
Francesca Garzillo
Erika Polgár
John S Riddell
Andrew J Todd
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2013
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-9-56

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Neurochemical characterisation of lamina II inhibitory interneurons that express GFP in the PrP-GFP mouse

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2013

Intrathecal leptin inhibits expression of the P2X2/3 receptors and alleviates neuropathic pain induced by chronic constriction sciatic nerve injury

Analgesic effect of a mixed T-type channel inhibitor/CB2 receptor agonist

ZIPping to pain relief: the role (or not) of PKMζ in chronic pain

Inhibition of tetrodotoxin-resistant sodium current in dorsal root ganglia neurons mediated by D1/D5 dopamine receptors

Voluntary movements as a possible non-reflexive pain assay

Electroacupuncture improves thermal and mechanical sensitivities in a rat model of postherpetic neuralgia