Opioid Poorly-Responsive Cancer Pain. Part 3. Clinical Strategies to Improve Opioid Responsiveness

Mercadante, Sebastiano; Portenoy, Russell K.

doi:10.1016/s0885-3924(01)00250-0

Cited by 83 publications

(39 citation statements)

References 160 publications

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“…In postherpetic neuralgia patients, a combination of systemic ketamine and morphine was more efficacious than either of the drugs alone [4]. Not all reports, however, show beneficial effects, and the overall clinical picture is mixed [152].…”

Section: Clinical Experiencementioning

confidence: 99%

NMDA Antagonists and Neuropathic Pain - Multiple Drug Targets and Multiple Uses

Chizh¹,

Headley²

2005

CPD

133

102

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NMDA (N-methyl-D-aspartate) receptors are one class of ionotropic receptor for the ubiquitous excitatory neurotransmitter L-glutamate. The receptor is made up of four protein subunits combined from a larger library of proteins, which gives this receptor a great deal of variability. This explains the large number of modulatory sites, a variety of sites at which antagonists can interact, and therefore a number of potential drug targets. Sensitivity of the NMDA ion channel to ambient levels of Mg++ gives it a voltage dependence that suits a function of responding to intense synaptic activation; the ability of the channel to admit Ca++ tends to trigger long-term processes. The receptor is thereby involved in long-term physiological processes such as learning and memory as well as in pathological processes such as neuropathic pain. Separating these functions therapeutically with NMDA antagonists has been a major difficulty, and has not yet been achieved with currently-available agents. This review summarises the preclinical rationale, based on animal models, and the clinical evidence on the use of NMDA antagonists in pain states. It also summarises the details of the receptor so as to explain the rationale for targeting either specific sites on the receptor, or exploiting anatomical differences in subtype expression, so as to provide the beneficial effects of NMDA receptor block with an improved side effect profile. In particular, agents that are selective for receptors that include the NR2B subunit preclinically have a substantially better profile for treating neuropathic pain than do current NMDA antagonists; some emerging clinical evidence supports this view.

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Section: Clinical Experiencementioning

confidence: 99%

NMDA Antagonists and Neuropathic Pain - Multiple Drug Targets and Multiple Uses

Chizh¹,

Headley²

2005

CPD

133

102

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“…7,31,32 However, although medications including nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors block the production of arachidonic acid metabolites, these medications are minimally effective in reducing cancer pain. 22,29 The poor efficacy of these drugs suggests that other mediators are likely responsible for intractable cancer pain. Cancer cells and associated cells in the tumor microenvironment (macrophages, neutrophils, and T cells) release a number of cytokines and enzymes that sensitize and/or directly excite primary afferent neurons.…”

Section: Original Report/connelly and Schmidtmentioning

confidence: 99%

Evaluation of pain in patients with oral squamous cell carcinoma

Connelly

Schmidt

2004

The Journal of Pain

111

137

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“…A stepwise scheme uses additive or perhaps synergistic effects of different substances. Nonopioid coanalgesics are not listed in this WHO scheme, but they are essential and can improve opioid effects in antinociceptive therapy [39]. Bisphosphonates and calcitonin are helpful for stabilizing bone metabolism.…”

Section: Pain From Urogenital Tumorsmentioning

confidence: 99%