Spinal transection reduces both spinal antinociception and CNS concentration of systemically administered morphine in rats

Advokat, Claire; Gulati, Anil

doi:10.1016/0006-8993(91)90349-z

Cited by 39 publications

(10 citation statements)

References 19 publications

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“…For example, less than 0.02% of an i.v. injected dose of morphine enters the brain (Advokat and Gulati, 1991;Banks and Kastin, 1994). These results may have implications for the role that blood-borne gp120 could play in neurotoxicity.…”

Section: Discussionmentioning

confidence: 86%

Characterization of lectin-mediated brain uptake of HIV-1 GP120

Banks

Kastin

1998

J. Neurosci. Res.

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The viral coat of the HIV-1 virus, gp120, has been shown to cross the blood-brain barrier (BBB) in lectin-like fashion by inducing adsorptive endocytosis (AE), a vesicular mechanism that could provide pathways into and across brain endothelial cells for virus and infected immune cells. Here, we extended those findings to show that gp120 slowly crossed the BBB with about 0.15% of an intravenously injected dose entering the brain after about 2 hr. The plant lectin glycoprotein wheat germ agglutinin (WGA) greatly enhanced gp120 crossing without disrupting the BBB. WGA enhanced the uptake of gp120 into all peripheral tissues studied, but the greatest percent increase occurred for brain, whereas another barrier tissue, the testis, had the least increase. Five other plant lectins tested had little or no effect on gp120 uptake by brain, suggesting a key role for sialic acid and N-acetyl-beta-D-glucosaminyl acid, the sugars to which WGA binds, in the uptake of gp120 by brain endothelial cells. WGA did not enhance the uptake of nonglycosylated gp120 and the uptake of gp120 was not self-inhibitable or altered by pretreatment of mice with aluminum. In conclusion, these studies show that gp120 crosses the BBB by a lectin-like mechanism resembling AE that is likely mediated by binding to specific sugar moieties and is rather selective for brain.

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Section: Discussionmentioning

confidence: 86%

Characterization of lectin-mediated brain uptake of HIV-1 GP120

Banks

Kastin

1998

J. Neurosci. Res.

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“…Interestingly, intrathecal morphine has been reported to be more effective in spinal than in intact rats ( Siuciak & Advokat, 1989 ). In addition, following systemic administration, the morphine concentration in the central nervous system was found to be significantly altered by spinal transection ( Advokat & Gulati, 1991 ). Taken together, these data make one cautious about drawing conclusions as to the effects of morphine on descending modulation.…”

Section: Discussionmentioning

confidence: 99%

Effects of sufentanil and NMDA antagonists on a C‐fibre reflex in the rat

Adam

Gairard

Chauvin

et al. 2001

British J Pharmacology

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1 The eects of intravenous sufentanil and pre-administration of N-methyl-D-aspartate (NMDA) receptor antagonists were tested on a re¯ex triggered by C-®bre activation. The re¯ex was elicited by electrical stimulation of the sural nerve and recorded from the ipsilateral biceps femoris muscle in halothane anaesthetized rats either (1) with an intact neuraxis or (2) in which the brain had previously been transected at the level of the obex. 2 All four doses of sufentanil (0.33, 0.6, 1 and 2 mg kg 71) elicited a depression of the re¯ex in a dose-dependent manner. However, following the expected depression, all doses of sufentanil elicited both facilitation of the re¯ex and tonic inter-stimulus discharges. 3 The C-®bre re¯ex was not modi®ed following intravenous ketamine (1 mg kg 71) or (+)-HA966 (5 or 10 mg kg 71) but, when administered 5 min before sufentanil, these drugs enhanced both the extent and the duration of the depression and strongly reduced the facilitations. 4 In the obex-transected rats, the depressive eect of 1 mg kg 71 sufentanil increased, while the facilitation of the C-®bre re¯ex and the tonic inter-stimulus discharges disappeared. Preadministration of 10 mg kg 71 (+)-HA966 reinforced and prolonged the depressive eect of sufentanil. 5 These results extend previous studies suggesting the involvement of NMDA receptors in the spinal transmission of nociceptive signals. They illustrate the potential of spinal NMDA receptor blockade to both enhance the analgesic, and prevent the pro-nociceptive, eects of sufentanil.

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“…Disruption of the dorsal part of the lateral funiculus abolishes the supraspinal antinociceptive effect of opiates (Hayes et al, 1978;Basbaum & Fields, 1984;Advokat & Gulati, 1991). Interestingly, there was a clear decrease in the potency of morphine in producing antinociception in spinally injured allodynic rats.…”

Section: Disassociated Anti-allodynic Effect Of Supraspinal Morphinementioning

confidence: 99%

Comparison of the anti‐allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain

Hao

et al. 1997

European Journal of Pain

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The present study has assessed the efficacy and potency of systemic, intrathecal (i.t.) and intracerebroventricular (i.c.v.) morphine in alleviating a chronic mechanical allodynia-like behaviour in a rat model of central pain after spinal cord injury. The anti-allodynic potency of morphine was compared to its antinociceptive potency in both spinally injured and normal rats. Systemic (intraperitoneal or subcutaneous) morphine did not significantly relieve allodynia up to 3 mg/kg cumulative dose, which was sedative. Mechanical allodynia-like behaviour was only significantly relieved by l0 mg/kg morphine which caused severe sedation. Low doses of i.c.v. morphine abolished vocalization of allodynic rats to von Frey hair stimulation. However, other components of abnormal reactions to innocuous mechanical stimulation, such as agitation, jumping and avoidance, were only relieved by i.c.v. morphine at high, sedative doses. In contrast, i.t. morphine dose dependently reversed all components of the allodynic reactions without causing sedation. Morphine administered by all three routes produced powerful antinociception in the tail flick test in normal rats. The antinociceptive potency of morphine was reduced after systemic, i.t. and, particularly, i.c.v. administration in allodynic rats. These results indicated that i.t. morphine relieved the mechanical allodynia-like responses in spinally injured rats, whereas systemic or i.c.v. morphine only increased the response threshold to innocuous mechanical stimulation at high doses, which was associated with sedation, making it difficult to assess the anti-allodynic effect. However, i.c.v. morphine may be particularly effective for the affective component of pain in the present model. The antinociceptive potency of morphine was also reduced in spinally injured rats. It is suggested that morphine may be differentially effective against different types of pain after different routes of administration. Spinal morphine may be a therapeutic alternative in treating central pain after spinal cord injury.

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Spinal transection reduces both spinal antinociception and CNS concentration of systemically administered morphine in rats

Cited by 39 publications

References 19 publications

Characterization of lectin-mediated brain uptake of HIV-1 GP120

Characterization of lectin-mediated brain uptake of HIV-1 GP120

Effects of sufentanil and NMDA antagonists on a C‐fibre reflex in the rat

Comparison of the anti‐allodynic and antinociceptive effects of systemic; intrathecal and intracerebroventricular morphine in a rat model of central neuropathic pain

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