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.
N1 - Funding Information:
Acknowledgements-We would like to thank MS Sandy Jacobs for typingt hem anuscripta, nd Dr John Taylor from Biomeasuref or providing the somatostatina nalog BIM-23003. This work was supportedb y NIH Grant DA 02110 (N.Y.), BurroughsW ellcomeF ellowship 1986/87(D .G.), and John G. SearleF ellowship,a nd NIH TeacherI nvesti-gator Award NSO0849(M .R.).
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.
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U2 - 10.1016/0306-4522(90)90259-7
DO - 10.1016/0306-4522(90)90259-7
M3 - Article
C2 - 1711172
AN - SCOPUS:0025687709
SN - 0306-4522
VL - 39
SP - 761
EP - 774
JO - Neuroscience
JF - Neuroscience
IS - 3
ER -