The Effects of Intrathecally Administered Opioid and Adrenergic Agents on Spinal Function

Yaksh, Tony L.

doi:10.1007/978-1-4684-4994-5_20

Cited by 7 publications

(6 citation statements)

References 120 publications

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“…regional glutamate availability caused by the GT downregulation would modulate the activity of excitatory amino acid receptors including NMDARs at both presynaptic and postsynaptic sites, considering that NMDARs as well as -opioid receptors are located both presynaptically and postsynaptically (Yaksh, 1986;Liu et al, 1994). This extends previous views of NMDA and -opioid receptor interactions that have focused on the postsynaptic site (Mao et al 1995b).…”

Section: Relation To Mechanisms Of Morphine Tolerance and Associated supporting

confidence: 72%

“…This is suggested by the observations that downregulation of GLT-1 and GLAST occurs in the rat's brain regions after an impaired cortical glutamatergic connection (Ginsberg et al, 1995), and conversely, that an increase in extracellular glutamate upregulates GLT-1 in astroglial cultures (Thorlin et al, 1998). If this is the case, a decreased level of extracellular glutamate resulting from the inhibitory effect of morphine on neurotransmitter (e.g., glutamate) release (Yaksh, 1986) could lead to a simultaneous downregulation of both EAAC1 and GLAST to maintain regional glutamate homeostasis. The present data showing a time course of progressive GT downregulation after chronic morphine would lend some support to this possibility.…”

Section: Potential Mechanisms Of Morphine-induced Gt Downregulationmentioning

confidence: 99%

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Chronic Morphine Induces Downregulation of Spinal Glutamate Transporters: Implications in Morphine Tolerance and Abnormal Pain Sensitivity

et al. 2002

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Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we examined the role of spinal glutamate transporters (GTs) in the development of both morphine tolerance and associated thermal hyperalgesia. Chronic morphine administered through either intrathecal boluses or continuous infusion induced a dose-dependent downregulation of GTs (EAAC1 and GLAST) in the rat's superficial spinal cord dorsal horn. This GT downregulation was mediated through opioid receptors because naloxone blocked such GT changes. Morphine-induced GT downregulation reduced the ability to maintain in vivo glutamate homeostasis at the spinal level, because the hyperalgesic response to exogenous glutamate was enhanced, including an increased magnitude and a prolonged time course, in morphine-treated rats with reduced spinal GTs. Moreover, the downregulation of spinal GTs exhibited a temporal correlation with the development of morphine tolerance and thermal hyperalgesia. Consistently, the GT inhibitor l-trans-pyrrolidine-2-4-dicarboxylate (PDC) potentiated, whereas the positive GT regulator riluzole reduced, the development of both morphine tolerance and thermal hyperalgesia. The effects from regulating spinal GT activity by PDC were at least in part mediated through activation of the NMDA receptor (NMDAR), because the noncompetitive NMDAR antagonist MK-801 blocked both morphine tolerance and thermal hyperalgesia that were potentiated by PDC. These results indicate that spinal GTs may contribute to the neural mechanisms of morphine tolerance and associated abnormal pain sensitivity by means of regulating regional glutamate homeostasis.

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Section: Relation To Mechanisms Of Morphine Tolerance and Associated supporting

confidence: 72%

Section: Potential Mechanisms Of Morphine-induced Gt Downregulationmentioning

confidence: 99%

Chronic Morphine Induces Downregulation of Spinal Glutamate Transporters: Implications in Morphine Tolerance and Abnormal Pain Sensitivity

et al. 2002

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“…Previous studies have shown that electrical or chemical stimulation of these areas can produce antinociceptive effects (Willis et al, 1977;Basbaum and Fields, 1978;Haber et al, 1980;Tattersall et al, 1986b;Hodge et al, 1986;Yaksh, 1986;Janss et al, 1987;Jones and Gebhart, 1988;Zhao and Duggan 1988;Burnett and Gebhart, 1991;Miller and Proudfit, 1991;Proudfit, 1992; through known descending projections (Westlund and Coulter, 1980;Kuypers and Martin, 1982).…”

Section: Functional Considerationsmentioning

confidence: 97%

Ascending projections from the area around the spinal cord central canal: APhaseolus vulgaris leucoagglutinin study in rats

Wang¹,

Willis²,

Westlund³

1999

J. Comp. Neurol.

117

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“…It is well known that opioids, at analgesic doses, produce inhibition or block excitation of dorsal horn cells by depression of their firing. 67 Morphine reduces the C fiber-evoked slow synaptic potential, and this may attenuate summation sufficiently to prevent windup. 68 Intrathecal morphine administered prior to or after a nerve injury reduces spinal hyperexcitability in acute animal experiments.…”

Section: The Effects Of Opioids On the Plastic Changes In The Central Nervous System After Injurymentioning

confidence: 99%

Opioid Poorly-Responsive Cancer Pain. Part 2

Mercadante

Portenoy

2001

Journal of Pain and Symptom Management

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The Effects of Intrathecally Administered Opioid and Adrenergic Agents on Spinal Function

Cited by 7 publications

References 120 publications

Chronic Morphine Induces Downregulation of Spinal Glutamate Transporters: Implications in Morphine Tolerance and Abnormal Pain Sensitivity

Chronic Morphine Induces Downregulation of Spinal Glutamate Transporters: Implications in Morphine Tolerance and Abnormal Pain Sensitivity

Ascending projections from the area around the spinal cord central canal: APhaseolus vulgaris leucoagglutinin study in rats

Opioid Poorly-Responsive Cancer Pain. Part 2

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