title: Activation of the beta-adrenoceptor-protein kinase A signaling pathway within the ventral bed nucleus of the stria terminalis mediates the negative affective component of pain in rats.
abstract: Pain is an unpleasant sensory and emotional experience. The neural systems underlying the sensory component of pain have been studied extensively, but we are only beginning to understand those underlying its affective component. The bed nucleus of the stria terminalis (BNST) has been implicated in stress responses and negative affective states, such as anxiety, fear, and aversion. Recently, we demonstrated the crucial role of the BNST in the negative affective component of pain using the conditioned place aversion (CPA) test. In the present study, we investigated the involvement of the beta-adrenoceptor-protein kinase A (PKA) signaling pathway within the BNST, in particular, within the ventral part of the BNST (vBNST), in pain-induced aversion in male Sprague Dawley rats. In vivo microdialysis showed that extracellular noradrenaline levels within the vBNST were significantly increased by intraplantar formalin injection. Using the CPA test, we found that intra-vBNST injection of timolol, a beta-adrenoceptor antagonist, dose-dependently attenuated the intraplantar-formalin-induced CPA (F-CPA) without reducing nociceptive behaviors. Experiments with subtype-selective antagonists demonstrated the essential role of beta(2)-adrenoceptors in F-CPA. Intra-vBNST injection of isoproterenol, a beta-adrenoceptor agonist, dose-dependently produced CPA even in the absence of noxious stimulation. This isoproterenol-induced CPA was reversed by the coinjection of Rp-cyclic adenosine monophosphorothioate (Rp-cAMPS), a selective PKA inhibitor. Furthermore, intra-vBNST injection of Rp-cAMPS dose-dependently attenuated the F-CPA. Together, these results suggest that PKA activation within the vBNST via the enhancement of beta-adrenergic transmission is important for the negative affective component of pain.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Deyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Katayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohno
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Masabumi
authors.initials: M
authors.lastname: Minami
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000342:Affective Symptoms / Q000378:metabolism / Q000523:psychology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases