Alpha lipoic acid attenuates evoked and spontaneous pain following surgical skin incision in rats

Abstract

Our previous studies have implicated Ca V 3.2 isoform of T-type Ca2+ channels (T-channels) in the development of postsurgical pain. We have also previously established that different T-channel antagonists can alleviate in vivo postsurgical pain. Here we investigated the analgesic potential of another T-channel blocker and endogenous antioxidant molecule, α-lipoic acid (ALA), in a postsurgical pain model in rats. Our in vivo results suggest that single and repetitive intraperitoneal injections of ALA after surgery or preemptively, significantly reduced evoked mechanical hyperalgesia following surgical paw incision. Furthermore, repeated preemptive systemic injections of ALA effectively alleviated spontaneous postsurgical pain as determined by dynamic weight-bearing testing. We expect that our preclinical study may lead to further investigation of analgesic properties and mechanisms of analgesic action of ALA in patients undergoing surgery.

Assessment of the analgesic effect of Alpha-lipoic acid by three acute pain models

“…The peak analgesic effect of lipoic acid was one hour after injection when using the water bath test. This result was harmonized with the study conducted on rats, which was interpreted by its long duration of action (3). There are several theories about the analgesic mechanism of alphalipoic acid.…”

“…The first method for eliciting pain was the pain model. Surgical Incisional pain model and Mechanical hyperalgesia (3), and to explain the putative mechanism of analgesia, it was revealed that V3.2-type calcium channels play an essential role in mechanical and thermal stimulation in rats and mice (3). A previous study on rats indicates ALA has an inhibitory effect on calcium channels type V3.2 in sensory neurons of the dorsal root ganglia of rats and reported that local injection of ALA reduced the sensation of heat and mechanical stimulation (4).…”

The role of voltage-gated calcium channels in the mechanisms of anesthesia and perioperative analgesia

“…In that context, we have recently shown that disruption of the Ca V 3.2 channel trafficking and recycling to the membrane (ubiquitination) in peripheral sensory neurons contributes to the development of postsurgical pain in rodents [32]. Additionally, in the same pain model, a natural antioxidant and T-type channel blocker such as alpha-lipoic acid alleviated both evoked and spontaneous pain in rats [33 ▪ ]. Importantly, it was shown in the same study that alpha-lipoic acid is effective when given systemically, either before or after onset of hyperalgesia induced with surgical paw incision.…”

Roles of AMPK and Its Downstream Signals in Pain Regulation

“…Berberine, a natural isoquinoline alkaloid, activates AMPK via either LKB1 or CaMKKβ [ 29 ]. The above activators have been applied as analgesics in experimental models of inflammatory pain, nerve injury, painful diabetic neuropathy and cancer pain [ 10 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Moreover, the short-term administration of metformin or AICAR can alleviate diabetic neuropathic pain without anti-diabetic effect [ 10 , 40 ].…”