Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 10 October 1997:
Vol. 278. no. 5336, pp. 275 - 279
DOI: 10.1126/science.278.5336.275
Prev | Table of Contents | Next

Reports

Inhibition of Hyperalgesia by Ablation of Lamina I Spinal Neurons Expressing the Substance P Receptor

Patrick W. Mantyh, * Scott D. Rogers, Prisca Honore, Brian J. Allen, Joseph R. Ghilardi, Jun Li, Randy S. Daughters, Douglas A. Lappi, Ronald G. Wiley, Donald A. Simone

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.

P. W. Mantyh, S. D. Rogers, P. Honore, B. J. Allen, J. R. Ghilardi, Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417; and Department of Preventive Sciences, School of Dentistry, University of Minnesota and the Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
J. Li, R. S. Daughters, D. A. Simone, Department of Preventive Sciences, School of Dentistry, University of Minnesota and the Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
D. A. Lappi, Advanced Targeting Systems, 1600 Faraday Avenue, Carlsbad, CA 92008, USA.
R. G. Wiley, Neurology Service (147), Veterans Administration Medical Center, Nashville, TN 37212, USA.
*   To whom correspondence should be addressed. E-mail: manty001{at}maroon.tc.umn.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Identifying Brain Activity Specifically Related to the Maintenance and Perceptual Consequence of Central Sensitization in Humans.
M. C. Lee, L. Zambreanu, D. K. Menon, and I. Tracey (2008)
J. Neurosci. 28, 11642-11649
   Abstract »    Full Text »    PDF »
Change of AMPA Receptors in Spinal Nociceptive Synapses during Inflammatory Hyperalgesia.
W. Wang and J. Huang (2008)
J. Neurosci. 28, 10185-10186
   Full Text »    PDF »
cGMP Produced by NO-Sensitive Guanylyl Cyclase Essentially Contributes to Inflammatory and Neuropathic Pain by Using Targets Different from cGMP-Dependent Protein Kinase I.
A. Schmidtko, W. Gao, P. Konig, S. Heine, R. Motterlini, P. Ruth, J. Schlossmann, D. Koesling, E. Niederberger, I. Tegeder, et al. (2008)
J. Neurosci. 28, 8568-8576
   Abstract »    Full Text »    PDF »
Translocation of GluR1-Containing AMPA Receptors to a Spinal Nociceptive Synapse during Acute Noxious Stimulation.
M. Larsson and J. Broman (2008)
J. Neurosci. 28, 7084-7090
   Abstract »    Full Text »    PDF »
Spinal cord mechanisms of pain.
R. D'Mello and A. H. Dickenson (2008)
Br. J. Anaesth. 101, 8-16
   Abstract »    Full Text »    PDF »
Long-term alterations of colonic nerve-mast cell interactions induced by neonatal maternal deprivation in rats.
F Barreau, C Salvador-Cartier, E Houdeau, L Bueno, and J Fioramonti (2008)
Gut 57, 582-590
   Abstract »    Full Text »    PDF »
Commonly Used Preclinical Models of Pain.
Y. Jeong and J. E. Holden (2008)
West J Nurs Res 30, 350-364
   Abstract »    PDF »
Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat.
K. S. Vikman, B. K. Rycroft, and M. J. Christie (2008)
J. Physiol. 586, 515-527
   Abstract »    Full Text »    PDF »
Neurokinin-1 Receptor Enhances TRPV1 Activity in Primary Sensory Neurons via PKC{varepsilon}: A Novel Pathway for Heat Hyperalgesia.
H. Zhang, C.-L. Cang, Y. Kawasaki, L.-L. Liang, Y.-Q. Zhang, R.-R. Ji, and Z.-Q. Zhao (2007)
J. Neurosci. 27, 12067-12077
   Abstract »    Full Text »    PDF »
4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
M. Trevisani, J. Siemens, S. Materazzi, D. M. Bautista, R. Nassini, B. Campi, N. Imamachi, E. Andre, R. Patacchini, G. S. Cottrell, et al. (2007)
PNAS 104, 13519-13524
   Abstract »    Full Text »    PDF »
Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto NK1 receptor-positive lamina I neurons in the rat dorsal horn.
B. K. Rycroft, K. S. Vikman, and M. J. Christie (2007)
J. Physiol. 580, 883-894
   Abstract »    Full Text »    PDF »
NK-1 Receptors Modulate the Excitability of ON Cells in the Rostral Ventromedial Medulla.
D. Budai, S. G. Khasabov, P. W. Mantyh, and D. A. Simone (2007)
J Neurophysiol 97, 1388-1395
   Abstract »    Full Text »    PDF »
Contribution of Substance P and Neurokinin A to the Differential Injury-Induced Thermal and Mechanical Responsiveness of Lamina I and V Neurons.
J. Mazario and A. I. Basbaum (2007)
J. Neurosci. 27, 762-770
   Abstract »    Full Text »    PDF »
Both Ca2+-permeable and -impermeable AMPA receptors contribute to primary synaptic drive onto rat dorsal horn neurons.
C.-K. Tong and A. B. MacDermott (2006)
J. Physiol. 575, 133-144
   Abstract »    Full Text »    PDF »
GABAA-Receptor Blockade Reverses the Injury-Induced Sensitization of Nociceptor-Specific (NS) Neurons in the Spinal Dorsal Horn of the Rat.
E. Garcia-Nicas, J. M. A. Laird, and F. Cervero (2006)
J Neurophysiol 96, 661-670
   Abstract »    Full Text »    PDF »
Synaptic amplifier of inflammatory pain in the spinal dorsal horn..
H. Ikeda, J. Stark, H. Fischer, M. Wagner, R. Drdla, T. Jager, and J. Sandkuhler (2006)
Science 312, 1659-1662
   Abstract »    Full Text »    PDF »
Safety Evaluation of Intrathecal Substance P-Saporin, a Targeted Neurotoxin, in Dogs.
J. W. Allen, P. W. Mantyh, K. Horais, N. Tozier, S. D. Rogers, J. R. Ghilardi, D. Cizkova, M. R. Grafe, P. Richter, D. A. Lappi, et al. (2006)
Toxicol. Sci. 91, 286-298
   Abstract »    Full Text »    PDF »
Pathway-specific bidirectional regulation of Ca2+/calmodulin-dependent protein kinase II at spinal nociceptive synapses after acute noxious stimulation..
M. Larsson and J. Broman (2006)
J. Neurosci. 26, 4198-4205
   Abstract »    Full Text »    PDF »
Disinhibition Opens the Gate to Pathological Pain Signaling in Superficial Neurokinin 1 Receptor-Expressing Neurons in Rat Spinal Cord.
C. Torsney and A. B. MacDermott (2006)
J. Neurosci. 26, 1833-1843
   Abstract »    Full Text »    PDF »
Attenuation of acid induced oesophagitis in VR-1 deficient mice.
K Fujino, S G de la Fuente, Y Takami, T Takahashi, and C R Mantyh (2006)
Gut 55, 34-40
   Abstract »    Full Text »    PDF »
A Comparison of Visceral and Somatic Pain Processing in the Human Brainstem Using Functional Magnetic Resonance Imaging.
P. Dunckley, R. G. Wise, M. Fairhurst, P. Hobden, Q. Aziz, L. Chang, and I. Tracey (2005)
J. Neurosci. 25, 7333-7341
   Abstract »    Full Text »    PDF »
Synaptic input of rat spinal lamina I projection and unidentified neurones in vitro.
A. Dahlhaus, R. Ruscheweyh, and J. Sandkuhler (2005)
J. Physiol. 566, 355-368
   Abstract »    Full Text »    PDF »
Developmental Abnormalities of Neuronal Structure and Function in Prenatal Mice Lacking the Prader-Willi Syndrome Gene Necdin.
S. Pagliardini, J. Ren, R. Wevrick, and J. J. Greer (2005)
Am. J. Pathol. 167, 175-191
   Abstract »    Full Text »    PDF »
Substance P inhibits progesterone conversion to neuroactive metabolites in spinal sensory circuit: A potential component of nociception.
C. Patte-Mensah, C. Kibaly, and A. G. Mensah-Nyagan (2005)
PNAS 102, 9044-9049
   Abstract »    Full Text »    PDF »
Inhibition by Spinal {micro}- and {delta}-Opioid Agonists of Afferent-Evoked Substance P Release.
I. Kondo, J. C. G. Marvizon, B. Song, F. Salgado, S. Codeluppi, X.-Y. Hua, and T. L. Yaksh (2005)
J. Neurosci. 25, 3651-3660
   Abstract »    Full Text »    PDF »
Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation.
S. Seki, K. A. Erickson, M. Seki, O. Nishizawa, Y. Igawa, T. Ogawa, W. C. de Groat, M. B. Chancellor, and N. Yoshimura (2005)
Am J Physiol Renal Physiol 288, F466-F473
   Abstract »    Full Text »    PDF »
Spinal Neurons That Express NK-1 Receptors Modulate Descending Controls That Project Through the Dorsolateral Funiculus.
S. G. Khasabov, J. R. Ghilardi, P. W. Mantyh, and D. A. Simone (2005)
J Neurophysiol 93, 998-1006
   Abstract »    Full Text »    PDF »
Distribution and Injury-Induced Plasticity of Cadherins in Relationship to Identified Synaptic Circuitry in Adult Rat Spinal Cord.
J. H. Brock, A. Elste, and G. W. Huntley (2004)
J. Neurosci. 24, 8806-8817
   Abstract »    Full Text »    PDF »
Characterization of Wide Dynamic Range Neurons in the Deep Dorsal Horn of the Spinal Cord in Preprotachykinin-A Null Mice In Vivo.
W. J. Martin, Y. Cao, and A. I. Basbaum (2004)
J Neurophysiol 91, 1945-1954
   Abstract »    Full Text »    PDF »
Medullary serotonergic neurones and adjacent neurones that express neurokinin-1 receptors are both involved in chemoreception in vivo.
E. E. Nattie, A. Li, G. Richerson, and D. A. Lappi (2004)
J. Physiol. 556, 235-253
   Abstract »    Full Text »    PDF »
Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia.
J. R. Ghilardi, C. I. Svensson, S. D. Rogers, T. L. Yaksh, and P. W. Mantyh (2004)
J. Neurosci. 24, 2727-2732
   Abstract »    Full Text »    PDF »
Distinctive membrane and discharge properties of rat spinal lamina I projection neurones in vitro.
R. Ruscheweyh, H. Ikeda, B. Heinke, and J. Sandkuhler (2004)
J. Physiol. 555, 527-543
   Abstract »    Full Text »    PDF »
Perceptual Correlates of Nociceptive Long-Term Potentiation and Long-Term Depression in Humans.
T. Klein, W. Magerl, H.-C. Hopf, J. Sandkuhler, and R.-D. Treede (2004)
J. Neurosci. 24, 964-971
   Abstract »    Full Text »    PDF »
Ontogeny of the Pre-Botzinger Complex in Perinatal Rats.
S. Pagliardini, J. Ren, and J. J. Greer (2003)
J. Neurosci. 23, 9575-9584
   Abstract »    Full Text »    PDF »
Neurokinin-1 Receptor-Expressing Neurons in the Amygdala Modulate Morphine Reward and Anxiety Behaviors in the Mouse.
C. A. Gadd, P. Murtra, C. De Felipe, and S. P. Hunt (2003)
J. Neurosci. 23, 8271-8280
   Abstract »    Full Text »    PDF »
Peptide Receptors as Molecular Targets for Cancer Diagnosis and Therapy.
J. C. Reubi (2003)
Endocr. Rev. 24, 389-427
   Abstract »    Full Text »    PDF »
Neurokinin-1 Projection Cells in the Rat Dorsal Horn Receive Synaptic Contacts from Axons That Possess {alpha}2C-Adrenergic Receptors.
M. J. Olave and D. J. Maxwell (2003)
J. Neurosci. 23, 6837-6846
   Abstract »    Full Text »    PDF »
Pain: new insights, new treatments?.
O. Skott (2003)
Am J Physiol Regulatory Integrative Comp Physiol 285, R30-R31
   Full Text »    PDF »
Direct interstitial infusion of NK1-targeted neurotoxin into the spinal cord: a computational model.
M. Sarntinoranont, M. J. Iadarola, R. R. Lonser, and P. F. Morrison (2003)
Am J Physiol Regulatory Integrative Comp Physiol 285, R243-R254
   Abstract »    Full Text »    PDF »
Synaptic Plasticity in Spinal Lamina I Projection Neurons That Mediate Hyperalgesia.
H. Ikeda, B. Heinke, R. Ruscheweyh, and J. Sandkuhler (2003)
Science 299, 1237-1240
   Abstract »    Full Text »    PDF »
In vivo activation of a mutant {micro}-opioid receptor by antagonist: Future direction for opiate pain treatment paradigm that lacks undesirable side effects.
P.-Y. Law, J. W. Yang, X. Guo, and H. H. Loh (2003)
PNAS 100, 2117-2121
   Abstract »    Full Text »    PDF »
Ablation of NK1 Receptors in Rat Nucleus Tractus Solitarii Blocks Baroreflexes.
J. Riley, L.-H. Lin, D. A. Chianca Jr, and W. T. Talman (2002)
Hypertension 40, 823-826
   Abstract »    Full Text »    PDF »
Spinal Neurons that Possess the Substance P Receptor Are Required for the Development of Central Sensitization.
S. G. Khasabov, S. D. Rogers, J. R. Ghilardi, C. M. Peters, P. W. Mantyh, and D. A. Simone (2002)
J. Neurosci. 22, 9086-9098
   Abstract »    Full Text »    PDF »
Projection Neurons in Lamina I of Rat Spinal Cord with the Neurokinin 1 Receptor Are Selectively Innervated by Substance P-Containing Afferents and Respond to Noxious Stimulation.
A. J. Todd, Z. Puskar, R. C. Spike, C. Hughes, C. Watt, and L. Forrest (2002)
J. Neurosci. 22, 4103-4113
   Abstract »    Full Text »    PDF »
Depressor and Tachypneic Responses to Chemical Stimulation of the Ventral Respiratory Group Are Reduced by Ablation of Neurokinin-1 Receptor-Expressing Neurons.
H. Wang, T. P. Germanson, and P. G. Guyenet (2002)
J. Neurosci. 22, 3755-3764
   Abstract »    Full Text »    PDF »
The NK1 receptor mediates both the hyperalgesia and the resistance to morphine in mice lacking noradrenaline.
L. Jasmin, D. Tien, D. Weinshenker, R. D. Palmiter, P. G. Green, G. Janni, and P. T. Ohara (2002)
PNAS 99, 1029-1034
   Abstract »    Full Text »    PDF »
Intestinal inflammation and activation of sensory nerve pathways: a functional and morphological study in the nematode infected rat.
R De Giorgio, G Barbara, P Blennerhassett, L Wang, V Stanghellini, R Corinaldesi, S M Collins, and G Tougas (2001)
Gut 49, 822-827
   Abstract »    Full Text »    PDF »
Hypocretin-2-Saporin Lesions of the Lateral Hypothalamus Produce Narcoleptic-Like Sleep Behavior in the Rat.
D. Gerashchenko, M. D. Kohls, M. Greco, N. S. Waleh, R. Salin-Pascual, T. S. Kilduff, D. A. Lappi, and P. J. Shiromani (2001)
J. Neurosci. 21, 7273-7283
   Abstract »    Full Text »    PDF »
Stressor Specificity of Central Neuroendocrine Responses: Implications for Stress-Related Disorders.
K. Pacak and M. Palkovits (2001)
Endocr. Rev. 22, 502-548
   Abstract »    Full Text »    PDF »
Inhibition of Neuropathic Pain by Selective Ablation of Brainstem Medullary Cells Expressing the {micro}-Opioid Receptor.
F. Porreca, S. E. Burgess, L. R. Gardell, T. W. Vanderah, T. P. Malan Jr, M. H. Ossipov, D. A. Lappi, and J. Lai (2001)
J. Neurosci. 21, 5281-5288
   Abstract »    Full Text »    PDF »
An Animal Model to Assess Aversion to Intra-oral Capsaicin: Increased Threshold in Mice Lacking Substance P.
C. T. Simons, J.-M. Dessirier, S. L. Jinks, and E. Carstens (2001)
Chem Senses 26, 491-497
   Abstract »    Full Text »    PDF »
Substance P Abolishes the Facilitatory Effect of ATP on Spontaneous Glycine Release in Neurons of the Trigeminal Nucleus Pars Caudalis.
Z.-M. Wang, S. Katsurabayashi, J.-S. Rhee, M. Brodwick, and N. Akaike (2001)
J. Neurosci. 21, 2983-2991
   Abstract »    Full Text »    PDF »
Osteoprotegerin Diminishes Advanced Bone Cancer Pain.
N. M. Luger, P. Honore, M. A. C. Sabino, M. J. Schwei, S. D. Rogers, D. B. Mach, D. R. Clohisy, and P. W. Mantyh (2001)
Cancer Res. 61, 4038-4047
   Abstract »    Full Text »
The NK1 Receptor Is Essential for the Full Expression of Noxious Inhibitory Controls in the Mouse.
H. Bester, C. De Felipe, and S. P. Hunt (2001)
J. Neurosci. 21, 1039-1046
   Abstract »    Full Text »    PDF »
Schwann Cells Are Removed from the Spinal Cord after Effecting Recovery from Paraplegia.
L. Jasmin, G. Janni, T. M. Moallem, D. A. Lappi, and P. T. Ohara (2000)
J. Neurosci. 20, 9215-9223
   Abstract »    Full Text »    PDF »
The Effects of KRN5500, a Spicamycin Derivative, on Neuropathic and Nociceptive Pain Models in Rats.
S. Abdi, N. Vilassova, I. Decosterd, N. Feroz, and D. Borsook (2000)
Anesth. Analg. 91, 955-959
   Abstract »    Full Text »    PDF »
{micro}-Opioid Receptors Often Colocalize with the Substance P Receptor (NK1) in the Trigeminal Dorsal Horn.
S. A. Aicher, A. Punnoose, and A. Goldberg (2000)
J. Neurosci. 20, 4345-4354
   Abstract »    Full Text »    PDF »
Cytoarchitectonic and immunohistochemical characterization of a specific pain and temperature relay, the posterior portion of the ventral medial nucleus, in the human thalamus.
A. Blomqvist, E.-T. Zhang, and A. D. Craig (2000)
Brain 123, 601-619
   Abstract »    Full Text »    PDF »
Selective Impairment of Corticotropin-Releasing Factor1 (CRF1) Receptor-Mediated Function Using CRF Coupled to Saporin.
D. Maciejewski-Lenoir, S. C. Heinrichs, X.-J. Liu, N. Ling, A. Tucker, Q. Xie, D. A. Lappi, and D. E. Grigoriadis (2000)
Endocrinology 141, 498-504
   Abstract »    Full Text »    PDF »
Cytosolic immunization allows the expression of preATF-saporin chimeric toxin in eukaryotic cells.
M. S. FABBRINI, D. CARPANI, M. R. SORIA, and A. CERIOTTI (2000)
FASEB J 14, 391-398
   Abstract »    Full Text »
Transmission of Chronic Nociception by Spinal Neurons Expressing the Substance P Receptor.
M. L. Nichols, B. J. Allen, S. D. Rogers, J. R. Ghilardi, P. Honore, N. M. Luger, M. P. Finke, J. Li, D. A. Lappi, D. A. Simone, et al. (1999)
Science 286, 1558-1561
   Abstract »    Full Text »
Isolectin B4-Positive and -Negative Nociceptors Are Functionally Distinct.
C. L. Stucky and G. R. Lewin (1999)
J. Neurosci. 19, 6497-6505
   Abstract »    Full Text »    PDF »
Distinct neurochemical features of acute and persistent pain.
A. I. Basbaum (1999)
PNAS 96, 7739-7743
   Abstract »    Full Text »    PDF »
Vanilloid (Capsaicin) Receptors and Mechanisms.
A. Szallasi and P. M. Blumberg (1999)
Pharmacol. Rev. 51, 159-212
   Abstract »    Full Text »    PDF »
The Distribution of Neurons Expressing Calcium-Permeable AMPA Receptors in the Superficial Laminae of the Spinal Cord Dorsal Horn.
H. S. Engelman, T. B. Allen, and A. B. MacDermott (1999)
J. Neurosci. 19, 2081-2089
   Abstract »    Full Text »    PDF »
The central questions in pain perception may be peripheral.
G. W. Pasternak (1998)
PNAS 95, 10354-10355
   Full Text »    PDF »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)