Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats

D. M. Gaumann, T. S. Grabow, T. L. Yaksh, S. J. Casey, M. Rodriguez

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Rats chronically implanted with intrathecal catheters received intrathecal injections (10 μl followed by 10 μl saline flush) of either saline (n = 5), somatostatin (100 μg, n = 10), the somatostatin analog BIM 23003 (100 μg, n = 5), the somatostatin analog SMS 201-995 (100 μg, n = 5), the substance P analog [d-Pro2, d-Trp7,9] SP (10 μg, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.

Original languageEnglish (US)
Pages (from-to)761-774
Number of pages14
JournalNeuroscience
Volume39
Issue number3
DOIs
StatePublished - 1990

Fingerprint

Dynorphins
Substance P
Somatostatin
Spinal Injections
Meninges
Octreotide
Spinal Cord
Peptides
Nociception
Paraplegia
Catheters
Hot Temperature
Skin
Injections

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats. / Gaumann, D. M.; Grabow, T. S.; Yaksh, T. L.; Casey, S. J.; Rodriguez, M.

In: Neuroscience, Vol. 39, No. 3, 1990, p. 761-774.

Research output: Contribution to journalArticle

Gaumann, D. M. ; Grabow, T. S. ; Yaksh, T. L. ; Casey, S. J. ; Rodriguez, M. / Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats. In: Neuroscience. 1990 ; Vol. 39, No. 3. pp. 761-774.
@article{b6d2321c8a734bdba25be919a007da4a,
title = "Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats",
abstract = "Rats chronically implanted with intrathecal catheters received intrathecal injections (10 μl followed by 10 μl saline flush) of either saline (n = 5), somatostatin (100 μg, n = 10), the somatostatin analog BIM 23003 (100 μg, n = 5), the somatostatin analog SMS 201-995 (100 μg, n = 5), the substance P analog [d-Pro2, d-Trp7,9] SP (10 μg, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.",
author = "Gaumann, {D. M.} and Grabow, {T. S.} and Yaksh, {T. L.} and Casey, {S. J.} and M. Rodriguez",
year = "1990",
doi = "10.1016/0306-4522(90)90259-7",
language = "English (US)",
volume = "39",
pages = "761--774",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

TY - JOUR

T1 - Intrathecal somatostatin, somatostatin analogs, substance P analog and dynorphin A cause comparable neurotoxicity in rats

AU - Gaumann, D. M.

AU - Grabow, T. S.

AU - Yaksh, T. L.

AU - Casey, S. J.

AU - Rodriguez, M.

PY - 1990

Y1 - 1990

N2 - Rats chronically implanted with intrathecal catheters received intrathecal injections (10 μl followed by 10 μl saline flush) of either saline (n = 5), somatostatin (100 μg, n = 10), the somatostatin analog BIM 23003 (100 μg, n = 5), the somatostatin analog SMS 201-995 (100 μg, n = 5), the substance P analog [d-Pro2, d-Trp7,9] SP (10 μg, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.

AB - Rats chronically implanted with intrathecal catheters received intrathecal injections (10 μl followed by 10 μl saline flush) of either saline (n = 5), somatostatin (100 μg, n = 10), the somatostatin analog BIM 23003 (100 μg, n = 5), the somatostatin analog SMS 201-995 (100 μg, n = 5), the substance P analog [d-Pro2, d-Trp7,9] SP (10 μg, n = 10), or dynorphin A (1-17) (20 nmol, n = 8). These doses (somatostatin, substance P and dynorphin A) were selected based on previous studies in which they caused significant motor deficits. Effects on thermal cutaneous nociception, behavior, motor function and spinal cord histopathology were evaluated. All peptides caused severe neurotoxicity, evidenced by flaccid hind leg paralysis and lumbar spinal neuronal degeneration, which was accompanied by an inflammatory reaction in meninges and spinal gray matter. Histopathological changes had developed within 24 h after injection of somatostatin, substance P analog and dynorphin A, showing mild to severe neuronal degeneration and mild inflammatory responses in spinal cord and meninges. Significant antinociceptive effects, due to severe neurotoxic effects, were only observed following intrathecal injection of SMS 201-995 and the substance P analog. Potential neurotoxic mechanisms of the different peptides are discussed.

UR - http://www.scopus.com/inward/record.url?scp=0025687709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025687709&partnerID=8YFLogxK

U2 - 10.1016/0306-4522(90)90259-7

DO - 10.1016/0306-4522(90)90259-7

M3 - Article

C2 - 1711172

AN - SCOPUS:0025687709

VL - 39

SP - 761

EP - 774

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -