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 char0acteristics 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 oligodeoxynu-cleotide, 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 oligodeoxynucleotidetreated 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 incisioninduced pain, although PLC[beta]3 does not play a major role in thermal nociception or mechanical nociception in normal conditions. Keywords: phospholipase C[beta]3, inflammatory pain, postoperative pain, thermal hyperalgesia, mechanical hyperalgesia