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The purinergic P2Y12 receptor regulates microglial activation, resulting in persistence and aggravation of pain in neuropathic and nociceptive pain models. We conducted a retrospective chart review to explore the analgesic potency of the P2Y12 receptor-specific antagonist, clopidogrel, for clinical management of postoperative pain in patients who underwent abdominal surgery. Twenty-seven patients with cardiovascular comorbidities, who underwent laparoscopic abdominal surgery and had ceased aspirin (ASP,  n  = 17) or clopidogrel (CLP,  n  = 10) for 14 days pre-operatively, were enrolled retrospectively. In both groups, the number of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) consumed for managing postoperative pain was compared using the chi-square test and Mann–Whitney test. Our results showed that from postoperative day (POD) 0 to POD 3, the average numerical rating reflecting the postoperative pain was comparable between the two groups (CLP: 4.0 ± 1.4 vs. ASP: 3.7 ± 0.8, P-value = 0.56). However, at POD 7, opioid consumption in the CLP-treated group (fentanyl-equivalent dose: 0.49 ± 0.56 mg) was significantly lower than that in the ASP-treated group (1.48 ± 1.35 mg, P-value = 0.037). After reaching a stable state by repeated systemic administration, clopidogrel sustained the analgesic efficacy for a certain period. In conclusion, microglial P2Y12 receptors may mediate signal transduction of postoperative nociceptive pain and enhance clinical opioid analgesia.

Clopidogrel, an ADP-P2Y12 Receptor Antagonist, Can Prevent Severe Postoperative Pain: A Retrospective Chart Review