Role of preprotachykinin A (TAC1) gene-derived peptides and the neurokinin 1 (NK1) receptor in acute nocifensive behaviours and hyperalgesia
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1
University of Pécs, Department of Pharmacology and Pharmacotherapy, Hungary
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2
Liverpool University, School of Biomedical Sciences, United Kingdom
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3
University of Bonn, Institute of Molecular Psychiatry, Germany
Substance P (SP) and neurokinin A (NKA) encoded by the preprotachykinin A (TAC1) gene are involved in neurogenic inflammation and pain via neurokinin 1 and 2 (NK1 and NK2) receptors, respectively, localized in the sensory cortex, spinal cord and primary sensory neurones. Therefore, we investigated the role of SP, NKA and the NK1 receptor in acute somatic and visceral nociception and inflammatory hypersensitivity using gene-deleted mice (TAC1-/- and NK1-/-). Formalin-evoked paw liftings and lickings in the early phase (0-5 min) induced by direct activation of sensory nerves was not altered by deleting either the TAC1 or the NK1 receptor genes. This nocifensive behaviour in the later phase (20-45 min) mediated by inflammatory mechanisms was significantly reduced in the TAC1-/- group. Abdominal contractions evoked by i.p. acetic acid were markedly decreased in TAC1-/- and NK1-/- mice. Attenuation of i.pl. resiniferatoxin-induced thermal allodynia mediated by peripheral mechanisms was greater in TAC1-/- than in NK1-/- mice, while mechanical hyperalgesia involving central sensitization was only decreased in the NK1-/- group. It can be concluded that SP and NKA are responsible for acute visceral and somatic chemonociception, but NK1 receptors mediate their effect only in the visceral region. Inflammatory thermal allodynia develops by these TAC1-encoded tachykinins, but only partially through NK1 receptors. Meanwhile, mechanical hyperalgesia is mediated predominantly by NK1 receptors.
Keywords:
Behaviour and cognition,
Neuroscience
Conference:
13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011.
Presentation Type:
Abstract
Topic:
Behaviour and cognition
Citation:
Hajna
Z,
Borbély
É,
Quinn
JP,
Zimmer
A,
Pintér
E,
Szolcsányi
J and
Helyes
Z
(2011). Role of preprotachykinin A (TAC1) gene-derived peptides and the neurokinin 1 (NK1) receptor in acute nocifensive behaviours and hyperalgesia.
Front. Neurosci.
Conference Abstract:
13th Conference of the Hungarian Neuroscience Society (MITT).
doi: 10.3389/conf.fnins.2011.84.00131
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Received:
03 Mar 2011;
Published Online:
23 Mar 2011.
*
Correspondence:
Dr. Z. Hajna, University of Pécs, Department of Pharmacology and Pharmacotherapy, Pécs, Hungary, zsofia.hajna@aok.pte.hu