BACKGROUND Repeated morphine treatment has been shown to induce transient receptor potential vanilloid type 1 (TRPV1) expression in the spinal cord, dorsal root ganglion (DRG), and sciatic nerve of a rat model. Increased TRPV1 expression may therefore play a role in morphine tolerance. In this study, we evaluated the hypothesis that blockage of TRPV1 may be useful as an adjunctive pain manageme...

INTRODUCTION Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. METHODS To better u...

Previous data suggest that the analgesic effect of morphine may be modulated by P-glycoprotein (P-gp) inhibition. The effects of the P-gp inhibitor GF120918 on brain distribution and antinociceptive effects of morphine were examined in a rat cerebral microdialysis model. Pretreatment with GF120918 increased both the area under the concentration-time curve of unbound morphine in brain extracellu...

BACKGROUND I.V. morphine titration (MT) allows adjustment of the dose needed for pain relief in the post-anaesthesia care unit (PACU). However, MT has limitations such as a delay to achieve pain relief. We thus assessed the effect of a fixed intraoperative loading dose of morphine administered before titration. METHODS One hundred patients who were undergoing major orthopaedic surgery were in...

This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a sta...

Bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor (SNSR). The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal (i.t.) administration of morphine for 7 d produced morphine tolerance in rats. Then the rats wer...

The tolerance and dependence after chronic medication with morphine are thought to be representative models for studying the plasticity, including the remodeling of neuronal networks. To test the hypothesis that changes in neuronal plasticity observed in opioid tolerance or dependence are derived from increased activity of the anti-opioid nociceptin system, the effects of chronic treatments wit...

Several variables have been reported to affect the expression of sex differences in the analgesic potency of morphine. Although the effect of genetic background on morphine analgesia has been well documented, the relevance of genotype to sex differences in morphine analgesia has rarely been considered. The present study investigated morphine dose-response relationships in male and female mice o...

The present study examined the role of the rostral ventrolateral medulla (RVLM) in the modulation of acetylcholine (ACh) release by morphine. We examined the effect of morphine on the release of ACh in the RVLM of freely moving rats using the in vivo microdialysis method. The basal level of ACh was 303.0 +/- 28.2 fmol/20 microliter/15 min in the presence of neostigmine (10 microM). Morphine at ...

Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory-depressant effects of the drug (Hill et al., 2016). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Ju...