Abstract
BackgroundClinically, 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.MethodsThermal 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.ResultsThe 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.ConclusionsThe 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.
Highlights
Cancer pain is a common symptom in cancer patients, and 70% of patients with advanced cancer can develop symptoms of pain [1]
The present study investigated the analgesic effect and tolerance of dezocine in combination with morphine in a rat bone cancer pain (BCP) model and detected the mRNA and protein expression of opioid receptors in periaqueductal gray (PAG) and spinal cord which may induced by morphine and/or dezocine, aiming to provide preliminary data on cotreatment therapy and opioid receptor-related mechanisms of cancer pain
In the BCP group, the defense time was prolonged over time, and there were significant differences compared with the sham group from day 5 (P < 0.05)
Summary
Cancer pain is a common symptom in cancer patients, and 70% of patients with advanced cancer can develop symptoms of pain [1]. Opioid coadministration to enhance antinociception and decrease tolerance has increasingly attracted the attention of clinicians and researchers [2, 3]. Opioid receptor agonists-antagonists, including dezocine, pentazocine and buprenorphine, are a class of opioid drugs that are widely used in clinical anesthesia and pain therapy. Yekkirala et al suggested that when the opioid receptor agonist-antagonist pentazocine was combined with morphine, pentazocine antagonized morphine-induced activation of μ receptors, weakening its analgesic effect [8]. 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
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