title: Opposing roles of corticotropin-releasing factor and neuropeptide Y within the dorsolateral bed nucleus of the stria terminalis in the negative affective component of pain in rats.
abstract: Pain is a complex experience composed of sensory and affective components. Although the neural systems of the sensory component of pain have been studied extensively, those of its affective component remain to be determined. In the present study, we examined the effects of corticotropin-releasing factor (CRF) and neuropeptide Y (NPY) injected into the dorsolateral bed nucleus of the stria terminalis (dlBNST) on pain-induced aversion and nociceptive behaviors in rats to examine the roles of these peptides in affective and sensory components of pain, respectively. In vivo microdialysis showed that formalin-evoked pain enhanced the release of CRF in this brain region. Using a conditioned place aversion (CPA) test, we found that intra-dlBNST injection of a CRF1 or CRF2 receptor antagonist suppressed pain-induced aversion. Intra-dlBNST CRF injection induced CPA even in the absence of pain stimulation. On the other hand, intra-dlBNST NPY injection suppressed pain-induced aversion. Coadministration of NPY inhibited CRF-induced CPA. This inhibitory effect of NPY was blocked by coadministration of a Y1 or Y5 receptor antagonist. Furthermore, whole-cell patch-clamp electrophysiology in dlBNST slices revealed that CRF increased neuronal excitability specifically in type II dlBNST neurons, whereas NPY decreased it in these neurons. Excitatory effects of CRF on type II dlBNST neurons were suppressed by NPY. These results have uncovered some of the neuronal mechanisms underlying the affective component of pain by showing opposing roles of intra-dlBNST CRF and NPY in pain-induced aversion and opposing actions of these peptides on neuronal excitability converging on the same target, type II neurons, within the dlBNST.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Ide
authors.forename: Taiki
authors.initials: T
authors.lastname: Hara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohno
authors.forename: Ryuta
authors.initials: R
authors.lastname: Tamano
authors.forename: Kana
authors.initials: K
authors.lastname: Koseki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Naka
authors.forename: Chikashi
authors.initials: C
authors.lastname: Maruyama
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kaneda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Masabumi
authors.initials: M
authors.lastname: Minami
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000342:Affective Symptoms / Q000188:drug therapy* / Q000209:etiology; D000704:Analysis of Variance; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000009:adverse effects* / Q000819:agonists / Q000037:antagonists & inhibitors; D003510:Cyclohexanes / Q000494:pharmacology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005557:Formaldehyde / Q000633:toxicity; D018756:GABA Antagonists / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000009:adverse effects* / Q000819:agonists; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D009478:Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D010146:Pain / Q000139:chemically induced / Q000150:complications*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: C471210:2-methyl-4-(N-propyl-N-cycloproanemethylamino)-5-chloro-6-(2,4,6-trichloranilino)pyrimidine; D000814:Aniline Compounds; C092926:BIBP 3226; D003510:Cyclohexanes; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D006727:Hormone Antagonists; D006728:Hormones; C410588:L 152804; D009478:Neuropeptide Y; D010446:Peptide Fragments; D011724:Pyridazines; D011743:Pyrimidines; D014966:Xanthenes; C116607:antisauvagine 30; D005557:Formaldehyde; D003346:Corticotropin-Releasing Hormone; D001120:Arginine; C049853:gabazine; D007736:Kynurenic Acid
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