Comparison of Adrenaline and Dexmedetomidine in Improving the Cutaneous Analgesia of Mexiletine in Response to Skin Pinpricks in Rats

Abstract

<b><i>Background:</i></b> Adrenaline (Adr) and dexmedetomidine (Dex) are commonly used adjuvants of local anesthetics; however, the difference in the improvement of analgesia of local anesthetics between the 2 adjuvants remains unclear. <b><i>Objective:</i></b> The objective of this experimental research was to evaluate the cutaneous analgesic effect of mexiletine (Mex) by coadministration with Dex or Adr. <b><i>Methods:</i></b> The effect of a nociceptive block was assessed based on the inhibition of the cutaneous trunci muscle reflex in response to skin pinpricks in rats. The analgesic activity of Mex alone and Mex coadministered with Dex or Adr was evaluated after subcutaneous injections. Subcutaneous injections of drugs or combinations include Mex 0.6, 1.8, and 6.0 μmol; Adr 13.66 nmol; Dex 1.05600 nmol; saline; and Mex 1.8 and 6.0 μmol, respectively, combined with Dex 0.01056, 0.10560, and 1.05600 nmol or Adr 0.55, 2.73, and 13.66 nmol, with each injection dose of 0.6 mL. <b><i>Results:</i></b> Subcutaneous injections of Mex elicited dose-related cutaneous analgesia. Compared with Mex (1.8 μmol), adding Dex or Adr to Mex (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action. Mex (6.0 μmol) combined with Dex or Adr extended the duration of cutaneous analgesia when compared with Mex (6.0 μmol) alone. A high dose of Adr is more effective with Mex 1.8 μmol than that of Dex, whereas medium and low doses were less effective. Mex 6.0 μmol combined with any dose of Adr is superior to that of Dex. <b><i>Conclusions:</i></b> Both Dex and Adr improve the sensory block and enhance the nociceptive block duration of Mex. But in most cases, Adr is superior to Dex. It may be that different mechanisms of action of the 2 adjuvants lead to the differences.