title: Isolation rearing reduces mechanical allodynia in a mouse model of chronic inflammatory pain.
abstract: Social isolation rearing in mice after weaning reduces pain sensitivity to acute pain, and this hypoalgesia is mediated by the descending serotonergic pain inhibitory system in which the spinal serotonin (5-HT)1A receptor is involved. However, it is not known whether isolation rearing affects pain sensitivity to neuropathic or inflammatory chronic pain. In this study, we examined the effects of isolation rearing on chronic pain induced by Freund's complete adjuvant (FCA) and partial sciatic nerve ligation using the von Frey test (to assess mechanical allodynia) and the plantar test (to assess thermal hyperalgesia). In the FCA model, isolation rearing reduced mechanical allodynia, but not thermal hyperalgesia. In contrast, isolation rearing had no effect on allodynia or hyperalgesia in the sciatic nerve ligation model. The isolation rearing-induced inhibition of allodynia was alleviated by intrathecal injection of WAY100635, a selective 5-HT1A receptor antagonist. FCA increased 5-HT turnover and decreased 5-HT1A receptor expression in the spinal cord of group-reared mice, while it did not have these effects in isolation-reared mice. These results suggest that FCA suppresses the serotonergic pain inhibitory system selectively in group-reared mice. Moreover, systemic administration of osemozotan, a selective 5-HT1A receptor agonist, inhibited FCA-induced mechanical allodynia in group-reared mice, and this effect of the drug was suppressed by intrathecal injection of WAY100635. Collectively, these findings suggest that isolation rearing selectively reduces FCA-induced mechanical allodynia in mice and that this effect is mediated by the activation of spinal 5-HT1A receptors.
authors.affiliation: Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Horiguchi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ago
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hasebe
authors.forename: Kosuke
authors.initials: K
authors.lastname: Higashino
authors.forename: Kazuki
authors.initials: K
authors.lastname: Asada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001483:Base Sequence; D059350:Chronic Pain / Q000503:physiopathology*; D017931:DNA Primers; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D012934:Social Isolation
chemical_list: D017931:DNA Primers
keywords: Freund's complete adjuvant (FCA); Isolation rearing; Mechanical allodynia; Serotonin (5-HT)(1A) receptor; Thermal hyperalgesia