title: Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats.
abstract: The neurosteroid allopregnanolone (AP) influences the excitability of the central nervous system by acting as a positive allosteric modulator of γ-aminobutyric acid type A (GABA(A)) receptors. Here, we investigated the role of AP and its therapeutic potential in rats that showed hyperalgesic behavior after undergoing spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of rats that underwent SNL were greater than the corresponding levels in control animals. More importantly, spinal AP levels in hyperalgesic rats were lower than those in the rats that did not develop hyperalgesia following SNL; in contrast, brain AP levels were comparable among these groups. No differences in serum AP levels were observed among the groups. In addition, intrathecal exogenous administration of AP showed the antihyperalgesic effects in hyperalgesic rats after SNL. These findings suggest that changes in spinal AP biosynthesis are involved in the pathogenesis of neuropathic pain following peripheral nerve injury, and pharmacological manipulation of this phenomenon may provide a potential therapeutic target for neuropathic pain.
authors: Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi, 783-8505, Japan. takashika@kochi-u.ac.jp
authors: Takashi
authors: T
authors: Kawano
authors: Tomohiro
authors: T
authors: Soga
authors: Haidong
authors: H
authors: Chi
authors: Satoru
authors: S
authors: Eguchi
authors: Fumimoto
authors: F
authors: Yamazaki
authors: Naoko
authors: N
authors: Kumagai
authors: Masataka
authors: M
authors: Yokoyama
mesh_terms: D000777:Anesthetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D009437:Neuralgia / Q000188:drug therapy; D018377:Neurotransmitter Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000188:drug therapy; D011280:Pregnanolone / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013127:Spinal Nerves / Q000293:injuries* / Q000378:metabolism
chemical_list: D000777:Anesthetics; D018377:Neurotransmitter Agents; D011280:Pregnanolone