Effects of recurrent withdrawal on spinal GABA release during chronic morphine infusion in the rat

Dunbar, Stuart A.; Karamian, Ivan; Yeatman, Amy; Zhang, Jiahui

doi:10.1016/j.ejphar.2006.02.007

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…It has also been shown that morphine treatment alters the expression of several receptors in the amygdala, including the GABA A receptor [29]. Moreover, chronic treatment of morphine leads to a decrease in GABAergic tonus [40], [41]. Our DNA microarray analysis confirms this down-regulation of GABA A receptor subunits (β3 and γ1) in DRG neurons induced by chronic morphine treatment.…”

Section: Discussionsupporting

confidence: 80%

Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

et al. 2014

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Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

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Section: Discussionsupporting

confidence: 80%

Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

et al. 2014

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“…Other explanations may include study population differences in initial opioid dose, duration of opioid use, rate of opioid cessation, presence of opioid rotation, other medications used during tapering, and number of times detoxified—all of which have been shown to influence OIH or WIH. 14,24,30,44,47,66,74,104,124,131 …”

Section: Discussionmentioning

confidence: 99%

“…6,29,51 Once opioids are stopped, the pain sensitivity can continue or seem to heighten temporarily because any pain-relieving effect opioids may have provided is eliminated, and the drug-opposite effect can take time to subside. 139 Also, in preclinical models, opioid withdrawal induces central changes in neurotransmitters, along with neuroimmune and neuroinflammatory mediators involved in nociception, 43,44 thus potentially intensifying pain beyond OIH. A general increase in pain sensitivity after opioid cessation can occur after acute 4,55 or chronic 66,109,132,144 opioid exposure, referred to by a variety of names including withdrawal-induced hyperalgesia (WIH).…”

Section: Introductionmentioning

confidence: 99%

Withdrawal-associated injury site pain (WISP): a descriptive case series of an opioid cessation phenomenon

Rieb

Norman

Martin

et al. 2016

Pain

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“…Specifically, OIH manifests as increased pain sensitivity, which could lead a patient to believe that they must consume more opioid than truly required to treat the original underlying pain condition. Furthermore, it is not clear if the hyperalgesia seen during opioid withdrawal is synonymous with OIH seen during continuous use, as preclinical studies have demonstrated a mechanistic difference [78,[83][84][85][86]. In the case of opioid withdrawal syndrome, hyperalgesia appears after abrupt termination of opioid use.…”

Section: Oih's Relationship To Addictionmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

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Effects of recurrent withdrawal on spinal GABA release during chronic morphine infusion in the rat

Cited by 10 publications

References 23 publications

Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

Withdrawal-associated injury site pain (WISP): a descriptive case series of an opioid cessation phenomenon

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

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