Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y

Michael H. Ossipov, En Tan Zhang, Cristina Carvajal, Luis Gardell, Remi Quirion, Yvan Dumont, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Prevention of nerve injury-induced tactile, but not thermal, hypersensitivity is achieved by ipsilateral lesions of the dorsal columns or lidocaine microinjection into the nucleus gracilis (n. gracilis). These and other data support the possibility that tactile hyperresponsiveness after nerve injury may be selectively mediated by a low-threshold myelinated fiber pathway to the n. gracilis. Here we identify a transmitter that might selectively mediate such injury-induced tactile hypersensitivity. Neuropeptide Y (NPY), normally not detected in the dorsal root ganglion (DRG) or in the n. gracilis of rats, became markedly upregulated at both sites and in the spinal cord after spinal nerve injury. Injury-induced NPY-IR occurred predominately in large-diameter DRG cells, and the NPY-IR in the n. gracilis was blocked by dorsal rhizotomy or dorsal column lesion. NPY microinjection into the n. gracilis of uninjured rats elicited reversible tactile, but not thermal, hypersensitivity only in the ipsilateral hindpaw. Administration of anti-NPY antiserum, but not control serum or preabsorbed serum, into the n. gracilis ipsilateral to nerve injury reversed tactile, but not thermal, hypersensitivity. Similarly, microinjection of the NPY antagonists NPY18-36 and (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]-methyl]-N2- (diphenylacetyl)-argininamide trifluoroacetate, into the n. gracilis ipsilateral to the injury reversed tactile, but not thermal, hypersensitivity. Antagonist administration into the contralateral n. gracilis had no effect on injury-induced hypersensitivity. These data suggest the selective mediation of nerve injury-induced tactile hypersensitivity by upregulated NPY via large fiber input to n. gracilis. Selective reversal of injury-induced tactile allodynia by NPY receptor antagonists would have significant implications for human neuropathic conditions.

Original languageEnglish (US)
Pages (from-to)9858-9867
Number of pages10
JournalJournal of Neuroscience
Volume22
Issue number22
StatePublished - Nov 15 2002

Fingerprint

Neuropeptide Y
Touch
Hypersensitivity
Wounds and Injuries
Microinjections
Hot Temperature
Spinal Ganglia
Neuropeptide Y Receptors
Rhizotomy
Trifluoroacetic Acid
Spinal Injuries
Spinal Nerves
Hyperalgesia
Lidocaine
Serum
Immune Sera
Spinal Cord

Keywords

  • Allodynia
  • Dorsal column nuclei
  • Dorsal columns
  • Neuropathic pain
  • Neuropeptide Y
  • Nucleus gracilis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ossipov, M. H., Zhang, E. T., Carvajal, C., Gardell, L., Quirion, R., Dumont, Y., ... Porreca, F. (2002). Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. Journal of Neuroscience, 22(22), 9858-9867.

Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. / Ossipov, Michael H.; Zhang, En Tan; Carvajal, Cristina; Gardell, Luis; Quirion, Remi; Dumont, Yvan; Lai, Josephine; Porreca, Frank.

In: Journal of Neuroscience, Vol. 22, No. 22, 15.11.2002, p. 9858-9867.

Research output: Contribution to journalArticle

Ossipov, MH, Zhang, ET, Carvajal, C, Gardell, L, Quirion, R, Dumont, Y, Lai, J & Porreca, F 2002, 'Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y', Journal of Neuroscience, vol. 22, no. 22, pp. 9858-9867.
Ossipov MH, Zhang ET, Carvajal C, Gardell L, Quirion R, Dumont Y et al. Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. Journal of Neuroscience. 2002 Nov 15;22(22):9858-9867.
Ossipov, Michael H. ; Zhang, En Tan ; Carvajal, Cristina ; Gardell, Luis ; Quirion, Remi ; Dumont, Yvan ; Lai, Josephine ; Porreca, Frank. / Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 22. pp. 9858-9867.
@article{890e765fef454926a15f25fcfc9fdb29,
title = "Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y",
abstract = "Prevention of nerve injury-induced tactile, but not thermal, hypersensitivity is achieved by ipsilateral lesions of the dorsal columns or lidocaine microinjection into the nucleus gracilis (n. gracilis). These and other data support the possibility that tactile hyperresponsiveness after nerve injury may be selectively mediated by a low-threshold myelinated fiber pathway to the n. gracilis. Here we identify a transmitter that might selectively mediate such injury-induced tactile hypersensitivity. Neuropeptide Y (NPY), normally not detected in the dorsal root ganglion (DRG) or in the n. gracilis of rats, became markedly upregulated at both sites and in the spinal cord after spinal nerve injury. Injury-induced NPY-IR occurred predominately in large-diameter DRG cells, and the NPY-IR in the n. gracilis was blocked by dorsal rhizotomy or dorsal column lesion. NPY microinjection into the n. gracilis of uninjured rats elicited reversible tactile, but not thermal, hypersensitivity only in the ipsilateral hindpaw. Administration of anti-NPY antiserum, but not control serum or preabsorbed serum, into the n. gracilis ipsilateral to nerve injury reversed tactile, but not thermal, hypersensitivity. Similarly, microinjection of the NPY antagonists NPY18-36 and (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]-methyl]-N2- (diphenylacetyl)-argininamide trifluoroacetate, into the n. gracilis ipsilateral to the injury reversed tactile, but not thermal, hypersensitivity. Antagonist administration into the contralateral n. gracilis had no effect on injury-induced hypersensitivity. These data suggest the selective mediation of nerve injury-induced tactile hypersensitivity by upregulated NPY via large fiber input to n. gracilis. Selective reversal of injury-induced tactile allodynia by NPY receptor antagonists would have significant implications for human neuropathic conditions.",
keywords = "Allodynia, Dorsal column nuclei, Dorsal columns, Neuropathic pain, Neuropeptide Y, Nucleus gracilis",
author = "Ossipov, {Michael H.} and Zhang, {En Tan} and Cristina Carvajal and Luis Gardell and Remi Quirion and Yvan Dumont and Josephine Lai and Frank Porreca",
year = "2002",
month = "11",
day = "15",
language = "English (US)",
volume = "22",
pages = "9858--9867",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "22",

}

TY - JOUR

T1 - Selective mediation of nerve injury-induced tactile hypersensitivity by neuropeptide Y

AU - Ossipov, Michael H.

AU - Zhang, En Tan

AU - Carvajal, Cristina

AU - Gardell, Luis

AU - Quirion, Remi

AU - Dumont, Yvan

AU - Lai, Josephine

AU - Porreca, Frank

PY - 2002/11/15

Y1 - 2002/11/15

N2 - Prevention of nerve injury-induced tactile, but not thermal, hypersensitivity is achieved by ipsilateral lesions of the dorsal columns or lidocaine microinjection into the nucleus gracilis (n. gracilis). These and other data support the possibility that tactile hyperresponsiveness after nerve injury may be selectively mediated by a low-threshold myelinated fiber pathway to the n. gracilis. Here we identify a transmitter that might selectively mediate such injury-induced tactile hypersensitivity. Neuropeptide Y (NPY), normally not detected in the dorsal root ganglion (DRG) or in the n. gracilis of rats, became markedly upregulated at both sites and in the spinal cord after spinal nerve injury. Injury-induced NPY-IR occurred predominately in large-diameter DRG cells, and the NPY-IR in the n. gracilis was blocked by dorsal rhizotomy or dorsal column lesion. NPY microinjection into the n. gracilis of uninjured rats elicited reversible tactile, but not thermal, hypersensitivity only in the ipsilateral hindpaw. Administration of anti-NPY antiserum, but not control serum or preabsorbed serum, into the n. gracilis ipsilateral to nerve injury reversed tactile, but not thermal, hypersensitivity. Similarly, microinjection of the NPY antagonists NPY18-36 and (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]-methyl]-N2- (diphenylacetyl)-argininamide trifluoroacetate, into the n. gracilis ipsilateral to the injury reversed tactile, but not thermal, hypersensitivity. Antagonist administration into the contralateral n. gracilis had no effect on injury-induced hypersensitivity. These data suggest the selective mediation of nerve injury-induced tactile hypersensitivity by upregulated NPY via large fiber input to n. gracilis. Selective reversal of injury-induced tactile allodynia by NPY receptor antagonists would have significant implications for human neuropathic conditions.

AB - Prevention of nerve injury-induced tactile, but not thermal, hypersensitivity is achieved by ipsilateral lesions of the dorsal columns or lidocaine microinjection into the nucleus gracilis (n. gracilis). These and other data support the possibility that tactile hyperresponsiveness after nerve injury may be selectively mediated by a low-threshold myelinated fiber pathway to the n. gracilis. Here we identify a transmitter that might selectively mediate such injury-induced tactile hypersensitivity. Neuropeptide Y (NPY), normally not detected in the dorsal root ganglion (DRG) or in the n. gracilis of rats, became markedly upregulated at both sites and in the spinal cord after spinal nerve injury. Injury-induced NPY-IR occurred predominately in large-diameter DRG cells, and the NPY-IR in the n. gracilis was blocked by dorsal rhizotomy or dorsal column lesion. NPY microinjection into the n. gracilis of uninjured rats elicited reversible tactile, but not thermal, hypersensitivity only in the ipsilateral hindpaw. Administration of anti-NPY antiserum, but not control serum or preabsorbed serum, into the n. gracilis ipsilateral to nerve injury reversed tactile, but not thermal, hypersensitivity. Similarly, microinjection of the NPY antagonists NPY18-36 and (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]-methyl]-N2- (diphenylacetyl)-argininamide trifluoroacetate, into the n. gracilis ipsilateral to the injury reversed tactile, but not thermal, hypersensitivity. Antagonist administration into the contralateral n. gracilis had no effect on injury-induced hypersensitivity. These data suggest the selective mediation of nerve injury-induced tactile hypersensitivity by upregulated NPY via large fiber input to n. gracilis. Selective reversal of injury-induced tactile allodynia by NPY receptor antagonists would have significant implications for human neuropathic conditions.

KW - Allodynia

KW - Dorsal column nuclei

KW - Dorsal columns

KW - Neuropathic pain

KW - Neuropeptide Y

KW - Nucleus gracilis

UR - http://www.scopus.com/inward/record.url?scp=0037112023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037112023&partnerID=8YFLogxK

M3 - Article

VL - 22

SP - 9858

EP - 9867

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 22

ER -