Phospholipase C Beta 3 Expressed In Mouse Drgs Is Involved In Inflammatory And Postoperative Pain

Background: Previous studies suggested that phospholipase C beta 3 (PLC beta 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 PLC beta 3-expressing dorsal root ganglion (DRG) neurons and involvement of PLC beta 3 in inflammatory and postoperative pain have not been fully investigated.Purpose: We evaluated neurochemical characteristics of PLC beta 3-expressing DRG neurons in mice and then we examined the effects of selective knockdown of PLC beta 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. PLC beta 3 antisense oligodeoxynucleotide or PLC beta 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 PLC beta 3 protein levels in DRGs were evaluated by Western blotting.Results: Immunohistochemical analysis showed that high proportion of the PLC beta 3-positive profiles were biotinylated isolectin B4-positive or transient receptor potential vanilloid subfamily 1-positive. PLC beta 3 protein level in DRGs during CFA-induced inflammation was comparable to that at baseline. Intrathecal administration of PLC beta 3 antisense oligodeoxynucleotide, which significantly suppressed PLC beta 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 PLC beta 3 antisense oligodeoxynucleotide also inhibited surgical incision-induced thermal and mechanical hyperalgesia.Conclusion: Our results uncover a unique role of PLC beta 3 in the development and maintenance of inflammatory pain induced by CFA application and in those of surgical incision-induced pain, although PLC beta 3 does not play a major role in thermal nociception or mechanical nociception in normal conditions.