Naphazoline and oxymetazoline are superior to epinephrine in enhancing the cutaneous analgesia of lidocaine in rats

This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of four adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous four adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED₅₀; median effective dose) was epinephrine [0.013 (0.012–0.014) μmol] > oxymetazoline [0.25 (0.22–0.28) μmol] > naphazoline [0.42 (0.34–0.53) μmol] = bupivacaine [0.43 (0.37–0.50) μmol] > xylometazoline [1.34 (1.25–1.45) μmol] > lidocaine [5.86 (5.11–6.72) μmol] > tetrahydrozoline [6.76 (6.21–7.36) μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P < 0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED₂₅, ED₅₀, and ED₇₅). Co-administration of lidocaine (ED₅₀) with four adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that four adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.