Antihyperalgesia induced by de novo endomorphin-2 biosynthesis in the spinal cord is mediated by an interaction between CART containing nociceptiv afferents and NPY expressing interneurons
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1
Semmelweis University, Department of Anatomy, Histology and Embryology, Hungary
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2
HAS Institute of Experimental Medicine, Hungary
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3
Semmelweis University, Department of Pharmacology and Pharmacotherapy, Hungary
Intrathecal (i.t.) administration of Ile-Pro-Ile (IPI), an inhibitor of dipeptidyl peptidase IV enzyme (DPP-IV), exerts antihyperalgesic action in carrageenan-induced hyperalgesia in the rat. Cocaine- and Amphetamine-Regulated Transcript (CART) peptide is present in peptidergic C primary afferents and is likely to have a significant role in spinal pain processing. The N-terminal sequence in rat CART(55-102) peptide is Ile-Pro-Ile. The peptide bond between Ile57 and Tyr58 may serve as a cleavage site for neutral endopeptidase, therefore IPI can possibly be generated in vivo. The aims of this study are: (i) to clarify if the presence of N-terminal IPI in the rat CART(55-102) peptide has a definite role in nociceptive information processing and (ii) to explore the anatomical bases of possible interactions among neuropeptides and their receptors contributing to spinal pain processing under pathological conditions. I.t. administration of IPI (3-30 nmol/rat) was antihyperalgesic in carrageenan-induced hindpaw inflammation. IPI-induced antihyperalgesia could be antagonized by the opioid receptor antagonist naloxone or by a specific antiserum to endomorphin-2. I.t. CART (3 nmol/rat) caused a moderate increase of nociceptive threshold and induced hindleg and tail movement abnormalities under the same conditions. Using fluorescent immunohistochemistry we demonstrated close appositions between CART/Substance P/Calcitonin Gene-Related Peptide-containing primary afferents and neuropeptide Y-expressing interneurons on neurokinin-1 receptor-positive neurons in the rat spinal dorsal horn. Pathological overexcitation of C fibers induced by chronic inflammation may create ideal conditions for the generation of the endogenous opioid endomorphin-2 by membrane-bound DPP-IV, when "switched" to synthase mode by IPI in the spinal cord which may be mediated by an interaction between CART-containing nociceptive afferents and NPY- expressing interneurons.
Conference:
IBRO International Workshop 2010, Pécs, Hungary, 21 Jan - 23 Jan, 2010.
Presentation Type:
Poster Presentation
Topic:
Sensory and motor systems
Citation:
Kozsurek
M,
Lukácsi
E,
Gyimesi
K,
Puskár
Z,
Barna
I,
Király
K and
Rónai
A
(2010). Antihyperalgesia induced by de novo endomorphin-2 biosynthesis in the spinal cord is mediated by an interaction between CART containing nociceptiv afferents and NPY expressing interneurons.
Front. Neurosci.
Conference Abstract:
IBRO International Workshop 2010.
doi: 10.3389/conf.fnins.2010.10.00236
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Received:
05 May 2010;
Published Online:
05 May 2010.
*
Correspondence:
Márk Kozsurek, Semmelweis University, Department of Anatomy, Histology and Embryology, Budapest, Hungary, mark@kozsurek.hu