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Neuroanatomical characterization of imidazoline I 2 receptor agonist‐induced antinociception
Author(s) -
Siemian Justin N.,
Jia Shushan,
Liu JianFeng,
Zhang Yanan,
Li JunXu
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13899
Subject(s) - idazoxan , imidazoline receptor , nucleus accumbens , chemistry , microinjections , agonist , pharmacology , antagonist , endocrinology , medicine , receptor , prazosin
Chronic pain is a significant public health problem with a lack of safe and effective analgesics. The imidazoline I 2 receptor (I 2 R) is a promising analgesic target, but the neuroanatomical structures involved in mediating I 2 R‐associated behaviors are unknown. I 2 Rs are enriched in the arcuate nucleus, dorsal raphe ( DR ), interpeduncular nucleus, lateral mammillary body, medial habenula, nucleus accumbens ( NA c) and paraventricular nucleus; thus, this study investigated the antinociceptive and hypothermic effects of microinjections of the I 2 R agonist 2‐(2‐benzofuranyl)‐2‐imidazoline hydrochloride (2‐ BFI ). In rats, intra‐ DR microinjections produced antinociception in complete Freund's adjuvant‐ and chronic constriction injury‐induced pain models. Intra‐ NA c microinjections produced antinociception and increased noxious stimulus‐associated side time in a place escape/avoidance paradigm. Intra‐ NA c pretreatment with the I 2 R antagonist idazoxan but not the D1 receptor antagonist SCH 23390 or the D2 receptor antagonist raclopride attenuated intra‐ NA c 2‐ BFI ‐induced antinociception. Intra‐ NA c idazoxan did not attenuate systemically administered 2‐ BFI ‐induced antinociception. Microinjections into the other regions did not produce antinociception, and in none of the regions produced hypothermia. These data suggest that I 2 R activation in some but not all I 2 R‐enriched brain regions is sufficient to produce antinociception and supports the theory that different I 2 R‐associated effects are mediated via distinct receptor populations, which may in turn be distributed differentially throughout the CNS .