Additive analgesic effect of dexmedetomidine and dezocine administered intrathecally in a mouse pain model

Abstract

BackgroundIt is known that dexmedetomidine can reduce opioid requirements and that there is a synergistic effect when dexmedetomidine and morphine (a full mu opioid receptor agonist) are administered together. However, it was unclear whether a synergistic or additive effect would be observed when dexmedetomidine was co-administered with a partial mu opioid receptor agonist. The present study was designed to elucidate such effects by intrathecally co-administering dexmedetomidine and dezocine, a partial mu receptor agonist, in a mouse pain model.MethodsC57 mice (N = 165) were randomly divided into 19 groups. The tail flick test was adopted to measure the antinociceptive effects of the tested agents. The mice were divided into saline and drug groups to investigate the dose-dependent analgesic effects. Each drug was administered at fixed doses alone and in combination with one of three doses of a second drug.ResultsDezocine (0.3125 - 1.25 μg) and dexmedetomidine (0.04 - 1 μg) both enhanced the tail withdrawal latency in dose-dependent fashions. Dexmedetomidine (0.04 - 1 μg) enhanced the analgesic effect of dezocine. Dezocine (0.3125 - 1.25 μg) enhanced the analgesic effect of dexmedetomidine. Compared with the individual drug effects, the combined effects of dezocine (0.625 μg) and dexmedetomidine (0.04 μg) were more potent 15 - 60 min after injection, but they remained similar to the sum of the effects of the two individual drugs.ConclusionsDexmedetomidine and dezocine produce an additive analgesic effect on acute nociception when administered simultaneously.

Dezocine as a potent analgesic: overview of its pharmacological characterization

“…Another study showed that dezocine in dose of 0.625-2.5 μg (it) significantly increased tail withdrawal latency for C57 mice [24]. Huang with colleagues also demonstrated that dezocine increased tail withdrawal latency within the dose range of 0.3125-1.25 μg (it) and produced highest effect around 43% [17].…”

“…The analgesic effects of dezocine have been demonstrated in a number of preclinical behavioral paradigms. The literature is reviewed here, particularly focusing on the effects of dezocine on acute and chronic pain with varying experimental conditions on behavioral outcomes [15][16][17][18][19]. The relevant studies are shown in Table 3.…”

Dexmedetomidine Attenuates Neuropathic Pain by Inhibiting P2X7R Expression and ERK Phosphorylation in Rats

“…There are three highly homologous subtypes of the α 2 -adrenoceptor: α 2 A, α 2 B, and α 2 C. Dexmedetomidine, a highly selective α 2 -adrenoceptor agonist, has been used for conscious sedation and as an adjunct for clinical anesthesia [ 8 9 10 ]. In animal experiments, dexmedetomidine has been shown to produce analgesic effects in models of neuropathic pain, but the mechanisms underlying these effects remain largely unknown [ 11 12 13 ].…”

The analgesic effects of dezocine in rats with chronic constriction injuries

“…Compared with morphine, the gold-standard analgesic, dezocine exhibits less physiological dependence, analgesic tolerance, and hyperalgesia [12]. Huang et al [13] reported that 4 dezocine combined with dexmedetomidine has an additive dose-dependent analgesic effect in a mice model of pain. Wu et al [14] reported that dezocine can inhibit the internalization of the κ-opioid receptor induced by agonists and weaken the activation of astrocytes and dependence of rat models on opioid drugs.…”