Home LiteratureArticle Details
PMID: 9221788 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: imaging peptide action in vivo.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 17 ·No. 15 ·1997-08-01 ·Pages 5921-7

Allen BJ, Rogers SD, Ghilardi JR, Menning PM, Kuskowski MA, Basbaum AI, Simone DA, Mantyh PW

Abstract

Dorsal root ganglia (DRG) neurons synthesize and transport substance P (SP) to the spinal cord where it is released in response to intense noxious somatosensory stimuli. We have shown previously that SP release in vivo causes a rapid and reversible internalization of SP receptors (SPRs) in dorsal horn neurons, which may provide a pharmacologically specific image of neurons activated by SP. Here, we report that noxious heat (43 degrees, 48 degrees, and 55 degrees C) and cold (10 degrees, 0 degrees, -10 degrees, and -20 degrees C) stimuli, but not innocuous warm (38 degrees C) and cold (20 degrees C) stimuli, applied to the hindpaw of anesthetized rats induce SPR internalization in spinal cord neurons that is graded with respect to the intensity of the thermal stimulus. Thus, with increasing stimulus intensities, both the total number of SPR+ lamina I neurons showing SPR internalization and the number of internalized SPR+ endosomes within each SPR immunoreactive neuron showed a significant increase. These data suggest that thermal stimuli induce a graded release of SP from primary afferent terminals and that agonist dependent receptor endocytosis provides evidence of a spatially and pharmacologically unique "neurochemical signature" after specific somatosensory stimuli.

MeSH Terms
Animals Male Microscopy, Confocal Neurons, Afferent/physiology Pain Measurement Rats Rats, Sprague-Dawley Spinal Cord/metabolism,ultrastructure Substance P/metabolism
Chemicals
Substance P
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Allen B J
Molecular Neurobiology Laboratory, Education and Clinical Center, Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
Rogers S D
Ghilardi J R
Menning P M
Kuskowski M A
Basbaum A I
Simone D A
Mantyh P W
References (47)
47 references, click to expand
  1. Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain.
    Neuroscience. 1996 Jan;70(1):201-9 PMID: 8848125
  2. Combined application of excitatory amino acids and substance P produces long-lasting changes in responses of primate spinothalamic tract neurons.
    Brain Res Brain Res Rev. 1993 May-Aug;18(2):227-46 PMID: 7687919
  3. Catecholamine receptors: structure, function, and regulation.
    Recent Prog Horm Res. 1993;48:277-90 PMID: 8441851
  4. Sustained isometric contraction of skeletal muscle results in release of immunoreactive neurokinins in the spinal cord of the anaesthetized cat.
    Neurosci Lett. 1991 Jan 28;122(2):191-4 PMID: 1851262
  5. Subtype-specific differences in the intracellular sorting of G protein-coupled receptors.
    J Biol Chem. 1993 Jan 15;268(2):763-6 PMID: 7678260
  6. The neuropharmacology of capsaicin: review of some recent observations.
    Pharmacol Rev. 1986 Sep;38(3):179-226 PMID: 3534898
  7. Painful sensation induced by a thermal cutaneous stimulus.
    Pain. 1983 Oct;17(2):109-37 PMID: 6417617
  8. Characterization of antibodies to the rat substance P (NK-1) receptor and to a chimeric substance P receptor expressed in mammalian cells.
    J Neurosci. 1994 Feb;14(2):834-45 PMID: 7507985
  9. Dual pathways of internalization of the cholecystokinin receptor.
    J Cell Biol. 1995 Mar;128(6):1029-41 PMID: 7896869
  10. Mechanisms of desensitization and resensitization of G protein-coupled neurokinin1 and neurokinin2 receptors.
    Mol Pharmacol. 1996 Mar;49(3):438-46 PMID: 8643083
  11. Enhancement of spinothalamic neuron responses to chemical and mechanical stimuli following combined micro-iontophoretic application of N-methyl-D-aspartic acid and substance P.
    Pain. 1991 Oct;47(1):85-93 PMID: 1722895
  12. Morphological characterization of substance P receptor-immunoreactive neurons in the rat spinal cord and trigeminal nucleus caudalis.
    J Comp Neurol. 1995 Jun 5;356(3):327-44 PMID: 7642798
  13. High levels of mRNA coding for substance P, somatostatin and alpha-tubulin are expressed by rat and rabbit dorsal root ganglia neurons.
    Peptides. 1989 Nov-Dec;10(6):1179-94 PMID: 2482965
  14. Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues.
    J Neurosci. 1989 Jan;9(1):258-79 PMID: 2536418
  15. Binding and internalization of neurotensin in hybrid cells derived from septal cholinergic neurons.
    Ann N Y Acad Sci. 1992;668:345-7 PMID: 1334390
  16. Differential roles of NMDA and non-NMDA receptor activation in induction and maintenance of thermal hyperalgesia in rats with painful peripheral mononeuropathy.
    Brain Res. 1992 Dec 11;598(1-2):271-8 PMID: 1362520
  17. Peripheral projections and neuropeptide coexistence in a subpopulation of fluoride-resistant acid phosphatase reactive spinal primary sensory neurons.
    Neurosci Lett. 1984 Sep 28;51(1):139-44 PMID: 6096769
  18. Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11344-8 PMID: 1722327
  19. Opiate analgesics inhibit substance P release from rat trigeminal nucleus.
    Nature. 1977 Aug 11;268(5620):549-51 PMID: 18681
  20. Multiple effects of phorbol esters in the rat spinal dorsal horn.
    J Neurosci. 1989 Oct;9(10):3606-17 PMID: 2571684
  21. Single C nociceptor responses and psychophysical parameters of evoked pain: effect of rate of rise of heat stimuli in humans.
    J Physiol. 1992 May;450:581-92 PMID: 1432719
  22. Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors.
    Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1009-13 PMID: 7508118
  23. Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation.
    Science. 1995 Jun 16;268(5217):1629-32 PMID: 7539937
  24. Characterization of the peptide and sensory neurotoxic effects of capsaicin in the guinea pig.
    J Neurosci. 1983 Oct;3(10):2064-74 PMID: 6194277
  25. Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin.
    Neuroscience. 1991;43(2-3):601-10 PMID: 1717888
  26. Substance P release from knee joint afferent terminals: modulation by opioids.
    Brain Res. 1988 Aug 23;458(2):319-24 PMID: 2463049
  27. Adrenergic receptors as models for G protein-coupled receptors.
    Annu Rev Neurosci. 1992;15:87-114 PMID: 1575451
  28. Neurokinin-1 receptors on lumbar spinothalamic neurons in the rat.
    Neuroscience. 1996 May;72(1):255-63 PMID: 8730722
  29. Adrenergic receptors: recent insights into their mechanism of activation and desensitization.
    Adv Second Messenger Phosphoprotein Res. 1993;28:1-9 PMID: 8398391
  30. Modulation of spinal excitability: co-operation between neurokinin and excitatory amino acid neurotransmitters.
    Trends Neurosci. 1994 Oct;17(10):432-8 PMID: 7530882
  31. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation.
    Nature. 1992 Apr 9;356(6369):521-3 PMID: 1373227
  32. Stimulus specificity of peripherally evoked substance P release from the rabbit dorsal horn in situ.
    Neuroscience. 1989;30(1):241-50 PMID: 2473412
  33. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo.
    Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2622-6 PMID: 7535928
  34. Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat.
    Brain Res. 1988 Jun 7;451(1-2):261-73 PMID: 2472190
  35. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu opioid.
    Neuron. 1991 Aug;7(2):319-26 PMID: 1678615
  36. Release of immunoreactive substance P in the spinal cord during development of acute arthritis in the knee joint of the cat: a study with antibody microprobes.
    Brain Res. 1990 Oct 8;529(1-2):214-23 PMID: 1704282
  37. Spinoparabrachial tract neurons showing substance P receptor-like immunoreactivity in the lumbar spinal cord of the rat.
    Brain Res. 1995 Mar 20;674(2):336-40 PMID: 7796113
  38. Gastrin-releasing peptide receptor-induced internalization, down-regulation, desensitization, and growth: possible role for cyclic AMP.
    Mol Pharmacol. 1994 Aug;46(2):235-45 PMID: 8078487
  39. Novel substance P antagonist, CP-96,345, blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P.
    Neurosci Lett. 1991 Oct 28;132(1):39-43 PMID: 1724068
  40. Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig. Binding of radioiodinated peptide.
    Acta Physiol Scand. 1980 May;109(1):97-105 PMID: 6160731
  41. Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo.
    Peptides. 1989 Nov-Dec;10(6):1127-31 PMID: 2482963
  42. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons.
    Brain Res. 1975 Dec 19;100(2):235-52 PMID: 1104079
  43. Agonist-induced internalization of the substance P (NK1) receptor expressed in epithelial cells.
    Biochem J. 1994 Oct 1;303 ( Pt 1):177-86 PMID: 7524481
  44. Specificity of receptor-G protein interactions. Discrimination of Gi subtypes by the D2 dopamine receptor in a reconstituted system.
    J Biol Chem. 1990 Mar 15;265(8):4507-14 PMID: 2137824
  45. Activation of protein kinase C promotes glutamate-mediated transmission at the neuromuscular junction of the mealworm.
    J Physiol. 1988 Jun;400:691-700 PMID: 2901491
  46. Peptides and the primary afferent nociceptor.
    J Neurosci. 1993 Jun;13(6):2273-86 PMID: 8501507
  47. Distribution of somatostatin receptors in normal and tumor tissue.
    Metabolism. 1990 Sep;39(9 Suppl 2):78-81 PMID: 2169575
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1997-08-01
Pages
5921-7
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6573203
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2