Role of Cytokines in Wound Healing Following Wound Catheter Analgesia in Rats.

BACKGROUND: Local analgesia administered through a wound catheter is widely used for postoperative pain control, yet its effects on wound healing remain incompletely understood. This study examined how levobupivacaine alone or combined with meloxicam or buprenorphine influences inflammatory markers, angiogenesis, apoptosis, and transforming growth factor β1 (TGF-β1) expression during wound healing in rats. METHODS: Thirty Sprague Dawley rats were assigned to five groups: control, saline, levobupivacaine (L), levobupivacaine/meloxicam (L/MEL), and levobupivacaine/buprenorphine (L/BUP). Treatments were administered via a wound catheter for three days. Blood and skin samples were collected before surgery and on days 3, 10, and 21. RESULTS: Levobupivacaine combined with meloxicam or buprenorphine caused fluctuations in white blood cell counts, while albumin levels remained stable. Angiogenesis in the L/MEL group was markedly increased compared with the control, saline, and levobupivacaine-only groups, but the newly formed vessels exhibited consistently narrow lumina during the early healing phase. Caspase-3-positive cells were most numerous in L/MEL during inflammatory and proliferative phases, whereas delayed caspase-3 activation was observed in L/BUP. TGF-β1 expression peaked in both adjuvant groups on days 3 and 10. CONCLUSIONS: Meloxicam and buprenorphine increased TGF-β1 expression, but their vascular effects differed considerably. Meloxicam induced a marked increase in angiogenesis, but the newly formed vessels were structurally immature, displaying uniformly narrow lumina and poor architectural organisation, which led to their subsequent regression. In contrast, buprenorphine supported the formation of more mature vascular structures, characterised by wider vessel lumina and a more organised vascular network. These findings demonstrate that adjuvants used with levobupivacaine can significantly modify angiogenic and apoptotic responses and should be carefully considered when selecting multimodal local analgesia strategies after surgery.