This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of 4 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 4 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 (ED ; 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 (ED , ED , and ED ). Co-administration of lidocaine (ED ) with 4 adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that 4 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.