Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice

Journal of Traditional Chinese Medicine, 2023 · DOI: 10.19852/j.cnki.jtcm.20230802.006 · Published: August 2, 2023

Alternative Medicine Pharmacology Pain Management

Simple Explanation

This study investigates berberine's effects on morphine's pain-relieving abilities and the development of tolerance and hyperalgesia (increased pain sensitivity) in mice. The researchers aimed to see if berberine could enhance morphine's effects and prevent these negative side effects. The researchers used different morphine tolerance models (acute, chronic, and established) in mice. They measured pain responses, as well as nitric oxide synthase (NOS) activity and nitric oxide (NO) levels in the spinal cord. They also studied how berberine interacts with nerve cells treated with NMDA, a substance that can cause nerve damage. The study found that berberine could indeed enhance and prolong morphine's pain-relieving effects, and it could also inhibit the development of morphine tolerance and hyperalgesia. It also showed a neuroprotective effect, possibly by blocking NMDA activity.

Study Duration

Not specified

Participants

C57BL/6J mice

Evidence Level

Animal study

Key Findings

1
Berberine can prolong the duration of morphine analgesia.
2
Berberine can inhibit the decrease of maximum possible analgesic effect (MPAE) and baseline latency in acute and chronic morphine tolerance models.
3
Berberine can rapidly reverse the decreased MPAE in the established tolerance model.

Research Summary

The study evaluated the effects of berberine on morphine analgesia, tolerance, and hyperalgesia in mice, utilizing acute, chronic, and established morphine tolerance models. The researchers measured pain responses, NOS activity, and NO levels in the spinal cord and investigated berberine's interaction with NMDA-treated nerve cells. The results indicated that berberine could enhance and prolong morphine's analgesic effects, inhibit the development of morphine-induced tolerance and hyperalgesia, and rapidly reverse established tolerance. It also showed a neuroprotective effect, possibly related to the inhibition of NMDA activity. The findings suggest that berberine may serve as an effective analgesic adjuvant, potentially reducing the clinical dosage of morphine, enhancing its duration of action, and preventing the development of morphine-induced tolerance and hyperalgesia.

Practical Implications

Analgesic Adjuvant

Berberine may be used in conjunction with morphine to enhance its pain-relieving effects.

Tolerance and Hyperalgesia Prevention

Berberine may help to prevent or delay the development of morphine tolerance and hyperalgesia in patients requiring long-term opioid therapy.

Neuroprotective Agent

Berberine's neuroprotective properties could be beneficial in mitigating neuronal injury associated with opioid use.

Study Limitations

1
The study was conducted on mice, and the results may not be directly applicable to humans.
2
Plasma concentrations of morphine after administration were not measured.
3
PKC levels were not detected in this study.

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