Zimelidine attenuates the development of tolerance to morphine-induced antinociception

Özdemir, Ercan; Gürsoy, Sinan; Bağcıvan, İhsan; Durmuş, Nedim; Altun, Ahmet

doi:10.4103/0253-7613.93851

Cited by 6 publications

(3 citation statements)

References 27 publications

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“…These results demonstrate that the R9-CBD3-A6K peptide exhibits a long-lasting effect without the development of tolerance within the 72 h continuous infusion. In contrast, opiates such as morphine have been shown to elicit antinociceptive tolerance within 2–3 days [38; 65; 92]. …”

Section: Resultsmentioning

confidence: 99%

Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Xie¹,

Chew²,

Yang³

et al. 2016

Pain

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Uncoupling the protein–protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2–CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2.2 and depolarization-evoked Ca2+ influx in rat dorsal root ganglia neurons. In vitro studies demonstrated suppression of excitability of small-to-medium diameter dorsal root ganglion and inhibition of subtypes of voltage-gated Ca2+ channels. Sprague-Dawley rats with tibial nerve injury had profound and long-lasting tactile allodynia and ongoing pain. Immediate administration of R9-CBD3-A6K produced enhanced dopamine release from the nucleus accumbens shell selectively in injured animals, consistent with relief of ongoing pain. R9-CBD3-A6K, when administered repeatedly into the central nervous system ventricles of naive rats, did not result in a positive conditioned place preference demonstrating a lack of abusive liability. Continuous subcutaneous infusion of R9-CBD3-A6K over a 24- to 72-hour period reversed tactile allodynia and ongoing pain, demonstrating a lack of tolerance over this time course. Importantly, continuous infusion of R9-CBD3-A6K did not affect motor activity, anxiety, depression, or memory and learning. Collectively, these results validate the potential therapeutic significance of targeting the CaV-CRMP2 axis for treatment of neuropathic pain.

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Section: Resultsmentioning

confidence: 99%

Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Xie¹,

Chew²,

Yang³

et al. 2016

Pain

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“…in this study, the TF test was performed in sedated animals, and a difference in TF latency did not appear during the measurement time of 60 min. Moreover, TF latency remained constant, and dispersion of the TF latency was more suppressed than the reported TF latency in conscious control animals [9,24]. The learning effect was controlled by use of a sedative (1% isoflurane), which does not affect TF latency [28].…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Animal Model of Epidural Anesthesia and Sedative Tail-Flick Test for Evaluating Local Anesthetic Effects in Rats

et al. 2013

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Abstract:The tail-flick (TF) test is the most frequently used method to measure pain levels and assess the effects of anesthesia. In this study, we performed the TF test in rats sedated via an indwelling epidural catheter and then examined the effectiveness of this method in evaluating the local anesthetic effects. First, an epidural catheter was inserted into the epidural space, and anesthetic [lidocaine (L) or lidocaine including adrenaline (AL)] or normal saline (NS) was administered. Under sedation, we measured the dose for disappearance of the TF response, time to TF response recovery, onset and regression of local anesthesia, as well as the effect of an added agent on its continuation. The time course of TF latency (% maximum possible effect) in the NS group did not change during the experiment. In the AL group, TF latency increased significantly more than baseline during the 30-min period after injection. This was also significantly higher than the latency in the NS group and the L group. In the L group, the TF latency increased significantly above baseline for 20 min after injection and was significantly higher than that in the NS group. Due to the fact that we were able to detect the effect of local anesthesia onset and regression, as well as the local anesthesia continuation action of an additive agent, in rats sedated via an indwelled epidural catheter, we consider our method to be an improvement over conventional methods.

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“…For example, coadministration of fluoxetine, amitriptyline and zimelidine (selective 5-HT uptake inhibitors) with morphine prevents the morphine analgesic tolerance. 17,116 Conversely, administered with either 1-tryptophan, the 5-HT precursor, accelerates the development of morphine tolerance. 117 These conflicting findings could probable caused by a distinct in 5-HT density in different synapses.…”

Section: Serotonin Receptors and Opioid Antinociceptive Tolerancementioning

confidence: 99%

The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

Özdemir

2017

Int J Basic Clin Pharmacol

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Continuous treatment with opioid analgesics, such as morphine, leads to the development of ant nociceptive tolerance in patients. Although a lot of information about antinociceptive, the pathophysiological mechanisms of tolerance to opioid analgesia are not yet completely understood. Proposed mechanisms for opioid analgesic tolerance comprise down-regulation of opioid receptors, reduction of sensitivity G-proteins, altered intracellular signalling pathway including nitric oxide, adenyl cyclase, and protein kinase C. Numerous physiological and behavioural studies have shown an interaction of the serotonergic system and opioid antinociception. The serotonin (5-HT) receptor system is a necessary component of the spinal and midbrain pain modulation circuit mediating opioid analgesia. Various types of serotonin receptors demonstrate different effects on morphine analgesia. Systemic administration of opioids rise 5-HT levels in the spinal cord dorsal horn and contribute to opioid analgesia in the normal state but reduce that in neuropathic pain via spinal 5-HT3 receptors. Spinal and supraspinal serotonergic neurons may also play a pathophysiological role in the development of morphine analgesic tolerance. Serotonin receptor subtypes show different effects on opioid tolerance. This review paper focus on the current understanding of the role of serotonin receptor systems in opioid analgesia and tolerance.

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Zimelidine attenuates the development of tolerance to morphine-induced antinociception

Cited by 6 publications

References 27 publications

Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Sustained relief of ongoing experimental neuropathic pain by a CRMP2 peptide aptamer with low abuse potential

Establishment of an Animal Model of Epidural Anesthesia and Sedative Tail-Flick Test for Evaluating Local Anesthetic Effects in Rats

The pathophysiological role of serotonin receptor systems in opioid analgesia and tolerance

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