title: Pregabalin alters nociceptive behavior and expression level of P2X3 receptor in the spinal dorsal horn in a rat model induced by chronic compression of the dorsal root ganglion.
abstract: P2X3 receptors are present in the spinal dorsal horn (SDH) and play an essential role in the regulation of nociception and pain. Pregabalin (PGB) has been used as a new antiepileptic drug in the treatment of neuropathic pain. However, it is unclear whether PGB-induced analgesia was associated with the P2X3 receptor in SDH. Here, rats were randomly divided into four groups (n = 12 per group), including 2 sham operation groups, which was treated by normal saline (Sham + NS group) or PGB (Sham + PGB group), other 2 groups with chronic compression of the dorsal root ganglion, a normal saline-treated CCD group (CCD+NS group), and a PGB-treated CCD group (CCD + PGB group). A rat model of neuropathic pain was used by compressing the right L4 and L5 dorsal root ganglia. Each group was evaluated using the mechanical withdrawal threshold (MWT). The mRNA and protein levels of the P2X3 receptor in the ipsilateral SDH were measured by RT-PCR, western blot, and immunofluorescence on 14 day after CCD operation. CCD rats showed the highest mechanical hyperalgesia and the lowest pain threshold in the four groups. Simultaneously, CCD rats showed higher P2X3 mRNA and protein expression in ipsilateral side of the SDH than the sham operation rats. However, the MWT was increased and expression of P2X3 mRNA and protein in the ipsilateral SDH in CCD rats was decreased 3 days after PGB treatment. Thus, PGB may partially reverse mechanical hyperalgesia in CCD rats by inhibiting P2X3 receptor expression in the ipsilateral SDH.
authors.affiliation: Department of Anesthesiology, Weifang Medical University, Shandong Province, People's Republic of China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Yu
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Liu
authors.forename: Donghong
authors.initials: D
authors.lastname: Cui
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000473:pathology*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects*; D000069583:Pregabalin; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D058477:Receptors, Purinergic P2X3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013117:Spinal Cord Compression / Q000150:complications* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D058477:Receptors, Purinergic P2X3; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
keywords: P2X3 receptor; Pregabalin; dorsal root ganglion; neuropathic pain; spinal dorsal horn