Neuronal loss in the rostral ventromedial medulla in a rat model of neuropathic pain

Journal of Neuroscience

Volumn 31, Issue 47, 2011, Pages 17028-17039

  Lan Leong, Mai ^a   Gu, Ming ^a,b   Speltz Paiz, Rebecca ^a   Stahura, Eleanor I ^a   Mottey, Neli ^a   Steer, Clifford J ^a   Wessendorf, Martin ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MARYLAND DENTAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5,7 DIHYDROXYTRYPTAMINE; NEUROTOXIN; TAUROURSODEOXYCHOLIC ACID;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ASTROCYTE; BRAIN STEM; CELL COUNT; CELL LOSS; CONTROLLED STUDY; GLIA CELL; IMMUNOREACTIVITY; MALE; MICROGLIA; NERVE CELL; NERVE CELL NECROSIS; NERVE INJURY; NERVE LIGATION; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PAIN THRESHOLD; PRIORITY JOURNAL; RAT; ROSTRAL VENTROMEDIAL MEDULLA; SEROTONINERGIC NERVE CELL; SPINAL CORD DORSAL HORN; SPINAL NERVE; WITHDRAWAL REFLEX;

ANIMALS; CELL COUNT; CELL DEATH; DISEASE MODELS, ANIMAL; MALE; MEDULLA OBLONGATA; NEURALGIA; NEURONS; PAIN MEASUREMENT; RATS; RATS, SPRAGUE-DAWLEY; SPINAL NERVES;

EID: 81855180513     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1268-11.2011     Document Type: Article

References (80)

1. Amir R, Devor M (2000) Functional cross-excitation between afferent Aand C-neurons in dorsal root ganglia. Neuroscience 95:189-195.
2. Björklund A, Baumgarten HG, Rensch A. (1975) 5,7-Dihydroxytryptamine: improvement of its selectivity for serotonin neurons in the CNS by pretreatment with desipramine. J Neurochem 24:833-835.
3. Blenk KH, Häbler HJ, Jänig W. (1997) Neomycin and gadolinium applied to an L5 spinal nerve lesion prevent mechanical allodynia-like behaviour in rats. Pain 70:155-165.
4. Blumberg H, Jänig W (1984) Discharge pattern of afferent fibers from a neuroma. Pain 20:335-353.
5. Bowker RM, Westlund KN, Coulter JD (1981) Origins of serotonergic projections to the spinal cord in rat: an immunocytochemical-retrograde transport study. Brain Res 226:187-199.
6. Burgess SE, Gardell LR, Ossipov MH, Malan TP Jr, Vanderah TW, Lai J, Porreca F (2002) Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci 22:5129-5136.
7. Bursch W, Paffe S, Putz B, Barthel G, Schulte-Hermann R (1990) Determination of the length of the histological stages of apoptosis in normal liver and in altered hepatic foci of rats. Carcinogenesis 11:847-853.
8. Carlson JD, Maire JJ, Martenson ME, Heinricher MM (2007) Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J Neurosci 27:13222-13231.
9. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55-63.
10. Coggeshall RE, Lekan HA, White FA, Woolf CJ (2001) A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord. J Comp Neurol 435:276-282.
11. Compton MM, Caron LA, Cidlowski JA (1987) Glucocorticoid action on the immune system. J Steroid Biochem 27:201-208.
12. de Novellis V, Siniscalco D, Galderisi U, Fuccio C, Nolano M, Santoro L, Cascino A, Roth KA, Rossi F, Maione S (2004) Blockade of glutamate mGlu5 receptors in a rat model of neuropathic pain prevents early overexpression of pro-apoptotic genes and morphological changes in dorsal horn lamina II. Neuropharmacology 46:468-479.
13. Devor M (2006) Responses of nerves to injury in relation to neuropathic pain. In: Wall and Melzack's textbook of pain (McMahon S, Koltzenburg M, eds), pp 905-927. London: Elsevier Limited.
14. Dogrul A, Ossipov MH, Porreca F (2009) Differential mediation of descending pain facilitation and inhibition by spinal 5HT-3 and 5HT-7 receptors. Brain Res 1280:52-59.
15. Fields HL, Vanegas H, Hentall ID, Zorman G (1983a) Evidence that disinhibition of brain stem neurones contributes to morphine analgesia. Nature 306:684-686.
16. Fields HL, Bry J, Hentall I, Zorman G (1983b) The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 3:2545-2552.
17. Fields HL, Heinricher MM, Mason P (1991) Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 14:219-245.
18. Fields HL, Malick A, Burstein R (1995) Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol 74:1742-1759.
19. Fuccio C, Luongo C, Capodanno P, Giordano C, Scafuro MA, Siniscalco D, Lettieri B, Rossi F, Maione S, Berrino L (2009) A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice. Eur J Pharmacol 603:42-49.
20. Gonçalves L, Almeida A, Pertovaara A (2007) Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of peripheral neuropathy. Eur J Neurosci 26:2188-2195.
21. Gu M, Wessendorf M (2007) Endomorphin-2-immunoreactive fibers selectively appose serotonergic neuronal somata in the rostral ventral medial medulla. J Comp Neurol 502:701-713.
22. Hassanzadeh P, Ahmadiani A (2006) Nitric oxide and c-Jun N-terminal kinase are involved in the development of dark neurons induced by inflammatory pain. Synapse 59:101-106.
23. Heinricher MM, Barbaro NM, Fields HL (1989) Putative nociceptive modulating neurons in the rostral ventromedial medulla of the rat: firing of on-and off-cells is related to nociceptive responsiveness. Somatosens Mot Res 6:427-439.
24. Hokfelt T, Zhang X, Wiesenfeld-Hallin Z (2006) Central consequences of peripheral nerve damage. In: Wall and Melzack's textbook of pain (McMahon S, Koltzenburg M, eds), pp 947-959. London: Elsevier.
25. Howard CV, Reed MG (1998) Unbiased stereology: three-dimensional measurement in microscopy. Oxford: BIOS.
26. Jalalvand E, Javan M, Haeri-Rohani A, Ahmadiani A (2008) Stress-and non-stress-mediated mechanisms are involved in pain-induced apoptosis in hippocampus and dorsal lumbar spinal cord in rats. Neuroscience 157:446-452.
27. Ji RR, Kohno T, Moore KA, Woolf CJ (2003) Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26:696-705.
28. Kalyuzhny AE, Arvidsson U, Wu W, Wessendorf MW (1996) mu-Opioid and delta-opioid receptors are expressed in brainstem antinociceptive circuits: studies using immunocytochemistry and retrograde tracttracing. J Neurosci 16:6490-6503.
29. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239-257.
30. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355-363.
31. Koltzenburg M, Lundberg LE, Torebjörk HE (1992) Dynamic and static components of mechanical hyperalgesia in human hairy skin. Pain 51:207-219.
32. Koltzenburg M, Torebjörk HE, Wahren LK (1994) Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 117:579-591.
33. Kwiat G, Basbaum AI (1992) The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat. Somatosens Mot Res 9:157-173.
34. Lawen A (2003) Apoptosis-an introduction. Bioessays 25:888-896.
35. Li Y, Dorsi MJ, Meyer RA, Belzberg AJ (2000) Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers. Pain 85:493-502.
36. Liu CN, Raber P, Ziv-Sefer S, Devor M (2001) Hyperexcitability in sensory neurons of rats selected for high versus low neuropathic pain phenotype. Neuroscience 105:265-275.
37. Liu NJ, Chakrabarti S, Schnell S, Wessendorf M, Gintzler AR (2011) Spinal synthesis of estrogen and concomitant membrane estrogen receptor signaling regulate spinal kappa-and mu-opioid receptor heterodimerization and female-specific spinal morphine antinociception. J Neurosci 31:11836-11845.
38. Maione S, Siniscalco D, Galderisi U, de Novellis V, Uliano R, Di Bernardo G, Berrino L, Cascino A, Rossi F (2002) Apoptotic genes expression in the lumbar dorsal horn in a model neuropathic pain in rat. Neuroreport 13:101-106.
39. McCleane GJ, Suzuki R, Dickenson AH (2003) Does a single intravenous injection of the 5HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A double-blinded, placebo-controlled crossover study. Anesth Analg 97:1474-1478.
40. Mei XP, Xu H, Xie C, Ren J, Zhou Y, Zhang H, Xu LX (2011) Post-injury administration of minocycline: an effective treatment for nerve-injury induced neuropathic pain. Neurosci Res 70:305-312.
41. Meisner JG, Marsh AD, Marsh DR (2010) Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury. J Neurotrauma 27:729-737.
42. Michaelis M, Liu X, Jänig W (2000) Axotomized and intact muscle afferents but no skin afferents develop ongoing discharges of dorsal root ganglion origin after peripheral nerve lesion. J Neurosci 20:2742-2748.
43. Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ (2002) Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 22:6724-6731.
44. Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201-211.
45. Ossipov MH, Hong Sun T, Malan P Jr, Lai J, Porreca F (2000) Mediation of spinal nerve injury induced tactile allodynia by descending facilitatory pathways in the dorsolateral funiculus in rats. Neurosci Lett 290:129-132.
46. Pertovaara A, Wei H, Hämäläinen MM (1996) Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats. Neurosci Lett 218:127-130.
47. Polgár E, Gray S, Riddell JS, Todd AJ (2004) Lack of evidence for significant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model. Pain 111:144-150.
48. Polgár E, Hughes DI, Arham AZ, Todd AJ (2005) Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain. J Neurosci 25:6658-6666.
49. Popken GJ, Farel PB (1997) Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods. JComp Neurol 386:8-15.
50. Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TP Jr, Ossipov MH, Lappi DA, Lai J (2001) Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the mu-opioid receptor. J Neurosci 21:5281-5288.
51. Porreca F, Ossipov MH, Gebhart GF (2002) Chronic pain and medullary descending facilitation. Trends Neurosci 25:319-325.
52. Quaglino D, Ronchetti IP (2001) Cell death in the rat thymus: a minireview. Apoptosis 6:389-401.
53. Rahman W, Suzuki R, Webber M, Hunt SP, Dickenson AH (2006) Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation. Pain 123:264-274.
54. Ramalho RM, Viana RJ, Low WC, Steer CJ, Rodrigues CM (2008) Bile acids and apoptosis modulation: an emerging role in experimental Alzheimer's disease. Trends Mol Med 14:54-62.
55. Reed MG, Howard CV (1998) Surface-weighted star volume: concept and estimation. J Microsc 190:350-356.
56. Ringkamp M, Eschenfelder S, Grethel EJ, Häbler HJ, Meyer RA, Jänig W, Raja SN (1999) Lumbar sympathectomy failed to reverse mechanical allodynia-and hyperalgesia-like behavior in rats with L5 spinal nerve injury. Pain 79:143-153.
57. Rodrigues CM, Steer CJ (2001) The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent. Expert Opin Investig Drugs 10:1243-1253.
58. Rodrigues CM, Fan G, Ma X, Kren BT, Steer CJ (1998) A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J Clin Invest 101:2790-2799.
59. Rodrigues CM, Spellman SR, Sola ́ S, Grande AW, Linehan-Stieers C, Low WC, Steer CJ (2002) Neuroprotection by a bile acid in an acute stroke model in the rat. J Cereb Blood Flow Metab 22:463-471.
60. Rodrigues CM, Sola S, Nan Z, Castro RE, Ribeiro PS, Low WC, Steer CJ (2003) Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats. Proc Natl Acad Sci USA 100:6087-6092.
61. Sanchez V, Lucas M, Sanz A, Goberna R (1992) Decreased protein kinase C activity is associated with programmed cell death (apoptosis) in freshly isolated rat hepatocytes. Biosci Rep 12:199-206.
62. Schmued LC, Swanson LW, Sawchenko PE (1982) Some fluorescent counterstains for neuroanatomical studies. J Histochem Cytochem 30:123-128.
63. Schoemaker MH, Conde de la Rosa L, Buist-Homan M, Vrenken TE, Havinga R, Poelstra K, Haisma HJ, Jansen PL, Moshage H (2004) Tauroursodeoxycholic acid protects rat hepatocytes from bile acidinduced apoptosis via activation of survival pathways. Hepatology 39:1563-1573.
64. Scholz J, Broom DC, Youn DH, Mills CD, Kohno T, Suter MR, Moore KA, Decosterd I, Coggeshall RE, Woolf CJ (2005) Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve. J Neurosci 25:7317-7323.
65. Sekiguchi M, Sekiguchi Y, Konno S, Kobayashi H, Homma Y, Kikuchi S (2009) Comparison of neuropathic pain and neuronal apoptosis following nerve root or spinal nerve compression. Eur Spine J 18:1978-1985.
66. Siniscalco D, Fuccio C, Giordano C, Ferraraccio F, Palazzo E, Luongo L, Rossi F, Roth KA, Maione S, de Novellis V (2007) Role of reactive oxygen species and spinal cord apoptotic genes in the development of neuropathic pain. Pharmacol Res 55:158-166.
67. Skagerberg G, Björklund A (1985) Topographic principles in the spinal projections of serotonergic and non-serotonergic brainstem neurons in the rat. Neuroscience 15:445-480.
68. Solá S, Aranha MM, Steer CJ, Rodrigues CM (2007) Game and players: mitochondrial apoptosis and the therapeutic potential of ursodeoxycholic acid. Curr Issues Mol Biol 9:123-138.
69. Sugimoto T, Bennett GJ, Kajander KC (1990) Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine. Pain 42:205-213.
70. Suzuki R, Rahman W, Hunt SP, Dickenson AH (2004) Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res 1019:68-76.
71. Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH (2005) Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain 117:292-303.
72. Vera-Portocarrero LP, Zhang ET, Ossipov MH, Xie JY, King T, Lai J, Porreca F (2006) Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization. Neuroscience 140:1311-1320.
73. Wallace J (2007) Update on pharmacotherapy guidelines for treatment of neuropathic pain. Pain Headache Rep 11:208-214.
74. Ward A, Brogden RN, Heel RC, Speight TM, Avery GS (1984) Ursodeoxycholic acid: a review of its pharmacological properties and therapeutic efficacy. Drugs 27:95-131.
75. Wei F, Guo W, Zou S, Ren K, Dubner R (2008) Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J Neurosci 28:10482-10495.
76. Wei F, Dubner R, Zou S, Ren K, Bai G, Wei D, Guo W (2010) Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. J Neurosci 30:8624-8636.
77. Wei H, Pertovaara A (1999) MK-801, an NMDA receptor antagonist, in the rostroventromedial medulla attenuates development of neuropathic symptoms in the rat. Neuroreport 10:2933-2937.
78. Whiteside GT, Munglani R (2001) Cell death in the superficial dorsal horn in a model of neuropathic pain. J Neurosci Res 64:168-173.
79. Winkler CW, Hermes SM, Chavkin CI, Drake CT, Morrison SF, Aicher SA (2006) Kappa opioid receptor (KOR) and GAD67 immunoreactivity are found in OFF and NEUTRAL cells in the rostral ventromedial medulla. J Neurophysiol 96:3465-3473.
80. Woolf CJ, Salter MW (2000) Neuronal plasticity: increasing the gain in pain. Science 288:17651769.