Donepezil attenuates the development of morphine tolerance in rats with cancer-induced bone pain: The role of cortical N-methyl-D-aspartate receptors

Zhang, Bo; Wu, Lingling; Zhu, Qianmei; Dong, Yanpeng; Sun, Li

doi:10.1016/j.neulet.2021.135678

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…Several mechanisms have been suggested for the development of morphine tolerance, including downregulation of MOR [40], inhibition of opioid receptor internalization [41], and activation of NMDARs [9]. However, evidences demostrate that neuronal apoptosis plays an important role in the development of morphine tolerance [15,42].…”

Section: Discussionmentioning

confidence: 99%

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Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia

et al. 2023

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Morphine is a drug used in chronic pain such as diabetic neuropathy, but the development of tolerance to its antinociceptive effect is an important clinical problem. Recently, it has been stated that morphineinduced neuronal apoptosis can stimulate morphine tolerance. Our aim in this study was to investigate the effects of aspirin on morphine-induced neuronal apoptosis and analgesic tolerance in rats with diabetic neuropathy. After morphine tolerance induction, the antinociceptive effects of aspirin (50 mg/kg) and morphine (5 mg/kg) were evaluated by thermal pain tests at 15 or 30 minute intervals.Streptozotocin (STZ, 65 mg/kg) was injected intraperitoneally to induce diabetic neuropathy. To evaluate apoptosis in dorsal root ganglion (DRG) tissue, ELISA kits were used to measure caspase-3, Bax and Bcl-2 levels. Apoptotic cells were detected histologically by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. Study results indicate that prior administration of aspirin to diabetic rats signi cantly increased the antinociceptive e cacy of morphine compared to morphine alone. Thermal pain tests showed that aspirin signi cantly reduced morphine tolerance in rats with diabetic neuropathy. Biochemical analysis revealed that aspirin signi cantly decreased the levels of proapoptotic proteins, caspase-3 and Bax, while increasing the anti-apoptotic Bcl-2 in DRG neurons. Semiquantitative scoring demonstrated that aspirin provided a signi cant reduction in apoptotic cell counts in diabetic rats. In conclusion, these data suggested that aspirin attenuated morphine antinociceptive tolerance through anti-apoptotic activity in diabetic rat DRG neurons. Further studies are needed to elucidate these effects of aspirin on morphine tolerance.

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Section: Discussionmentioning

confidence: 99%

“…Different mechanisms have been proposed for morphine tolerance. These include nitric oxide (NO)-cGMP and mammalian target of rapamycin (mTOR) signaling pathways, glial cell and N-methyl-D-aspartate receptor (NMDAR) activation, opioid receptor desensitization, and ghrelin receptor inactivation [7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia

et al. 2023

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“…These signs may be mitigated by administration of drugs like clonidine and methadone 7 . Multilayered mechanisms have been associated with opioid tolerance and dependence such as the generation of free radicals, down-regulation of opioid receptors and activation of the N-methyl-Daspartate (NMDA) glutamatergic receptor [8][9] .…”

Section: Introductionmentioning

confidence: 99%

Xylopic acid from Xylopia aethiopica (Annonaceae) inhibits morphine tolerance in rats

Mante¹,

Abakah-Ewusi²,

Mingle³

et al. 2022

Pharm Sci Asia

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Traditionally, Xylopia aethiopica is used to manage pain disorders such as neuralgia, colic pain, rheumatism and headache. Using animal models, this study aimed to investigate the ability of Xylopic Acid (XA), a kaurene diterpene obtained from Xylopia aethiopica, to cause tolerance when administered alone or combined with morphine. Development of withdrawal symptoms on discontinuation was also investigated. Tolerance to morphine was induced in rats through an 8-day regimen of chronic administration of morphine (10 mg/kg; twice daily). Effects of XA alone (100 mg/kg) or XA (10-100 mg/kg) on morphine tolerance and withdrawal syndrome precipitated with naloxone hydrochloride (3 mg/kg) were also assessed. XA's mechanism of action was then explored through drug-receptor binding.Chronic morphine administration in rats resulted in analgesic tolerance and morphine withdrawal syndrome. Chronic XA administration did not result in tolerance to XA's antinociceptive effect. Development of morphine withdrawal syndrome precipitated by naloxone and morphine tolerance was significantly (F(12, 60)=29.88, p<0.0001) inhibited by XA. Xylopic acid inhibited development of diarrhea, jumps and weight loss. Pretreatment with α-2-adrenoceptor antagonist, yohimbine, 5HT3 antagonist, ondansetron and muscarinic antagonist, atropine, significantly (p=0.0042) blocked the inhibitory effect of XA on withdrawal jumps. Pretreatment with naloxone produced similar effects on withdrawal jumps as XA alone. Drug-receptor binding assays revealed a lack of significant interaction of XA on alpha-2 adrenoceptors (A, B, C) but exhibited significant DOR-selective antagonism similar to naltrindole. This study reveals that xylopic acid significantly inhibits morphine antinociceptive tolerance and withdrawal in rats. This is the first report of xylopic acid's antagonism on delta opioidergic receptors and potential as an inhibitor of chronic morphine tolerance.

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Cognitive Enhancers: What They Are and How They Are Used in Heroin Addiction

Shen

Mei

Liu

et al. 2022

Handbook of Substance Misuse and Addictions

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Donepezil attenuates the development of morphine tolerance in rats with cancer-induced bone pain: The role of cortical N-methyl-D-aspartate receptors

Cited by 6 publications

References 31 publications

Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia

Aspirin attenuates morphine antinociceptive tolerance in rats with diabetic neuropathy by inhibiting apoptosis in the dorsal root ganglia

Xylopic acid from Xylopia aethiopica (Annonaceae) inhibits morphine tolerance in rats

Cognitive Enhancers: What They Are and How They Are Used in Heroin Addiction

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