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Mechanisms of nociception evoked by intrathecal high-dose morphine.

Abstract：

:Morphine is recommended by WHO as the analgesic of choice for effective treatment of moderate to severe cancer pain . Indeed spinally administered morphine at small doses injected intrathecally (i.t.) or intracerebroventricularly into animals produces a profound antinociception at both spinal and supraspinal sites. Conversely, high doses of spinally administered morphine elicit a series of scratching, biting and licking in mice, and vocalization and agitation in rats, indicative of a spontaneous nociceptive behavioural response. Hyperalgesia and allodynia are also induced by such morphine treatment in humans as well as animals. These behaviours are not an opioid receptor-mediated event. This article will review the potential mechanisms of spinally mediated nociceptive behaviour evoked by i.t. morphine at high concentrations. We will discuss a possible presynaptic release of nociceptive neurotransmitters/neuromodulators (e.g., substance P, glutamate and dynorphin) in the primary afferent fibers following i.t. high-dose morphine. There must be an intimate interaction of i.t. high-dose morphine with tachykinin neurokinin 1 (NK1) receptors and multiple sites on the N-methyl-D-aspartate (NMDA) receptor complex in the dorsal spinal cord. Since the effect of NMDA receptor activation and the associated Ca2+ influx results in production of nitric oxide (NO) by activation of NO synthase, it seems that spinal NO also plays an important role in nociception evoked by i.t. high-dose morphine. Morphine-3-glucuronide, one of the major metabolites of morphine, has been found to evoke nociceptive behaviour similar to that of i.t. high-dose morphine. It is plausible that morphine-3-glucuronide may be responsible for nociception seen after i.t. high-dose morphine treatment. The demonstration of neural mechanism underlying morphine-induced nociception provides a pharmacological basis for improved pain management with morphine at high doses.

journal_name

Neurotoxicology

journal_title

Neurotoxicology

authors

Sakurada T,Komatsu T,Sakurada S

doi

10.1016/j.neuro.2004.12.011

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

801-9

issue

5

eissn

0161-813X

issn

1872-9711

pii

S0161-813X(05)00054-9

journal_volume

26

pub_type

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