Journal of Pain Research (Dec 2020)
Phospholipase Cβ3 Expressed in Mouse DRGs is Involved in Inflammatory and Postoperative Pain
Abstract
Susumu Ide,1 Tomoyuki Kawamata,1,2 Kumiko Ishida,1 Satoshi Fuseya,1 Takashi Ishida,1 Yuki Sugiyama,1 Mikito Kawamata,1 Satoshi Tanaka1 1Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Department of Anesthesiology, Wakayama Medical University, Wakayama, JapanCorrespondence: Susumu Ide; Satoshi TanakaDepartment of Anesthesiology and Resuscitology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, JapanTel +812-6337-2670Fax +812-6335-2734Email [email protected]; [email protected]: Previous studies suggested that phospholipase Cβ 3 (PLCβ 3), which is a common downstream component in the signaling cascade, plays an important role in peripheral mechanisms of perception including nociception. However, detailed profiles of PLCβ 3-expressing dorsal root ganglion (DRG) neurons and involvement of PLCβ 3 in inflammatory and postoperative pain have not been fully investigated.Purpose: We evaluated neurochemical char0acteristics of PLCβ 3-expressing DRG neurons in mice and then we examined the effects of selective knockdown of PLCβ 3 expression in DRGs on inflammatory and postoperative pain.Methods: Male C57BL/6-strain mice were used. For the inflammatory model, each mouse received subcutaneous injection of complete Freund’s adjuvant (CFA) in the left hindpaw. For the postoperative pain model, a plantar incision was made in the left hindpaw. PLCβ 3 antisense oligodeoxynucleotide or PLCβ 3 mismatch oligodeoxynucleotide was intrathecally administered once a day for three consecutive days in each model. The time courses of thermal hyperalgesia and mechanical hyperalgesia were investigated. Changes in PLCβ 3 protein levels in DRGs were evaluated by Western blotting.Results: Immunohistochemical analysis showed that high proportion of the PLCβ 3-positive profiles were biotinylated isolectin B4-positive or transient receptor potential vanilloid subfamily 1-positive. PLCβ 3 protein level in DRGs during CFA-induced inflammation was comparable to that at baseline. Intrathecal administration of PLCβ 3 antisense oligodeoxynucleotide, which significantly suppressed PLCβ 3 expression in DRGs, did not affect pain thresholds in normal conditions but inhibited CFA-induced thermal and mechanical hyperalgesia both at the early and late phases compared to that in mismatch oligodeoxynucleotide-treated mice. Intrathecal administration of PLCβ 3 antisense oligodeoxynucleotide also inhibited surgical incision-induced thermal and mechanical hyperalgesia.Conclusion: Our results uncover a unique role of PLCβ 3 in the development and maintenance of inflammatory pain induced by CFA application and in those of surgical incision-induced pain, although PLCβ 3 does not play a major role in thermal nociception or mechanical nociception in normal conditions.Keywords: phospholipase Cβ 3, inflammatory pain, postoperative pain, thermal hyperalgesia, mechanical hyperalgesia
