Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain

Abstract

Background Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. Methods Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord. Results The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord. Conclusions The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.

Administration of flurbiprofen axetil and dezocine for the postoperative analgesia in patients with non‑small cell lung cancer: A randomized, controlled study

“…In the present study, flurbiprofen axetil plus dezocine exhibited a stronger analgesic effect than monotherapy, as determined by decreased postoperative VAS scores and PCA consumption in patients with NSCLC. This was due to the following reasons: Flurbiprofen axetil suppressed inflammatory cytokines, such as TNF-α in the local injury of peripheral nerves, while dezocine acted on the µ-and κ-opioid receptors in the brain; therefore, their combination may exhibit a stronger analgesic effect by two different mechanisms and further lead to reduced postoperative pain compared with monotherapy in patients with resectable NSCLC (10,24).…”

The analgesic effects of dezocine in rats with chronic constriction injuries

“…In sham operation and model group, the concentration of dezocine was 0 mg/kg. Overall, 2.5, 5.0, and 10.0 mg/kg dezocine was administered in the D1, D2, and D3 groups, respectively [17]. The other two groups were given the same amount of normal saline.…”