Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors

Sakurada, Tsukasa; Watanabe, Chizuko; Okuda, Kazuhiro; Sugiyama, Akinori; Moriyama, Toshiyuki; Sakurada, Chikai; Tan-No, Koichi; Sakurada, Shinobu

doi:10.1016/s0169-328x(01)00332-1

Cited by 26 publications

(8 citation statements)

References 52 publications

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“…Perhaps most intriguing is the finding that OIH occurs independently of opioid receptors [42,77,[93][94][95][96], and is not a consequence of either prior or concurrent opioid receptor activity [42]. As such, research spanning nearly two decades has focused on understanding how OIH manifests without direct involvement of the opioid receptor system, the main findings of which are summarized in the following sections.…”

Section: The Neurobiology Of Oihmentioning

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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Section: The Neurobiology Of Oihmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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“…Morphine-evoked behavioural responses in mice are shown to be nonreversible with naloxone pretreatment. Rather dose-dependent inhibition is achieved using intrathecal administration of NMDA receptor antagonist or NMDA ion channel blocker [26].…”

Section: Key Pointsmentioning

confidence: 99%

Opioid-induced hyperalgesia

Bannister

2015

Current Opinion in Supportive &Amp; Palliative Care

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“…Instead, dose-dependent inhibition was achieved using intrathecal administration of NMDA receptor antagonist or NMDA ion channel blocker. 62 Translating research from bench to clinic, and corroborating animal model and patient case data regarding OIH, is crucial. Reassuringly, a recent study showed that naloxone did not reverse the hyperalgesia experienced by healthy human volunteers who were briefly exposed to remifentanil.…”

Section: Opioid-induced Hyperalgesiamentioning

confidence: 99%

“…Instead, dose-dependent inhibition was achieved using intrathecal administration of NMDA receptor antagonist or NMDA ion channel blocker. 62…”

Section: Opioid-induced Hyperalgesiamentioning

confidence: 99%

Cancer pain physiology

Falk

Bannister

Dickenson

2014

British Journal of Pain

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Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur. This model prompted related approaches, and we can now state that cancer pain may include elements of inflammatory and neuropathic pains but also unique changes in sensory processing. Cancer-induced bone pain results in progressive bone destruction, elevated osteoclast activity and distinctive nocifensive behaviours (indicating the triad of ongoing, spontaneous and movement-induced hyperalgesia). In addition, cancer cells induce an inflammatory infiltrate and release growth factors, cytokines, interleukins, chemokines, prostanoids and endothelins, resulting in a reduction of pH to below 5 and direct deformation of primary afferents within bone. These peripheral changes, in turn, drive hypersensitivity of spinal cord sensory neurons, many of which project to the parts of the brain involved in the emotional response to pain. Within the spinal cord, a unique neuronal function reorganization within segments of the dorsal horn of the spinal cord receiving nociceptive input from the bone are discussed. Changes in certain neurotransmitters implicated in brain modulation of spinal function are also altered with implications for the affective components of cancer pain. Treatments are described in terms of mechanistic insights and in the case of opioids, which modulate pain transmission at spinal and supraspinal sites, their use can be compromised by opioid-induced hyperalgesia. We discuss evidence for how this comes about and how it may be treated.

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Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors

Cited by 26 publications

References 52 publications

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

Opioid-induced hyperalgesia

Cancer pain physiology

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