Local Anesthetic-like Inhibition of Voltage-gated Na+Channels by the Partial μ-opioid Receptor Agonist Buprenorphine

Abstract

Buprenorphine is a potent local anesthetic and blocks voltage-gated Na(+) channels via the local anesthetic binding site. This property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia.

Effects of local and spinal administrations of mu-opioids on postoperative pain in aged vs adult mice

“…Buprenorphine is also capable of inhibiting and modulating voltage-gated sodium-channels [24]. The mu-agonist effect of buprenorphine models a bell-shaped distribution [43], and it is reported to be at least 100 times more potent than morphine [37].…”

Opioids Resistance in Chronic Pain Management

“…Partial agonists with mixed agonist-antagonist action are generally not indicated for the treatment of chronic pain [94], however, in 2011 the Food and Drug Administration has approved a transdermal formulation of buprenorphine for treatment of moderate to severe chronic pain [86]. Interestingly, buprenorphine may also act as a potent local anesthetic and blocks voltage-gated sodium channels via the local anesthetic binding site [95] and this property is likely to be relevant when buprenorphine is used for pain treatment and for local anesthesia. Ideally, the greatest analgesic activity would be obtained by a drug able to activate µ receptors and to inhibit k receptors.…”

In patients undergoing fast track total knee arthroplasty, addition of buprenorphine to a femoral nerve block has no clinical advantage

“…Fields et al [5] described the presence of multiple opiate receptor sites on primary afferent nerve fibers. [5] On the other hand, Leffler et al [6] showed that buprenorphine also has an inhibitory effect on voltage-gated Na(+) channels, thereby acting as a local anesthetic. [6] Clinically, buprenorphine added to a local anesthetic leads to longer lasting postoperative analgesia in some types of blocks.…”

“…[5] On the other hand, Leffler et al [6] showed that buprenorphine also has an inhibitory effect on voltage-gated Na(+) channels, thereby acting as a local anesthetic. [6] Clinically, buprenorphine added to a local anesthetic leads to longer lasting postoperative analgesia in some types of blocks. [7–12] More recently, Kosel et al [13] found lower numeric rating scale (NRS) pain scores with buprenorphine added to single-shot bupivacaine femoral nerve blocks in patients undergoing total knee arthroplasty.…”