Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section

We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previ...

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Veröffentlicht in:European journal of pharmacology 1999-04, Vol.370 (1), p.17-22
Hauptverfasser: Xu, Isabella S, Grass, Stefan, Wiesenfeld-Hallin, Zsuzsanna, Xu, Xiao-Jun
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Grass, Stefan
Wiesenfeld-Hallin, Zsuzsanna
Xu, Xiao-Jun
description We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092–2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED 50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED 50 for reflex depression was 2.4 μg for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED 50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.
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As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092–2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED 50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED 50 for reflex depression was 2.4 μg for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED 50 for reflex depression being 374 ng. 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As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092–2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED 50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED 50 for reflex depression was 2.4 μg for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED 50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.</description><subject>Animals</subject><subject>Antinociception</subject><subject>Biological and medical sciences</subject><subject>Carrageenan</subject><subject>Dose-Response Relationship, Drug</subject><subject>Excipients</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Inflammation - chemically induced</subject><subject>Injections, Spinal</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Nerve injury</subject><subject>Neuropathic pain</subject><subject>Nociceptin</subject><subject>Opioid</subject><subject>Opioid Peptides - administration &amp; dosage</subject><subject>Opioid Peptides - pharmacology</subject><subject>Pain - drug therapy</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Reflex - drug effects</subject><subject>Regression Analysis</subject><subject>Sciatic Nerve - injuries</subject><subject>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. 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Psychology</topic><topic>Inflammation - chemically induced</topic><topic>Injections, Spinal</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Nerve injury</topic><topic>Neuropathic pain</topic><topic>Nociceptin</topic><topic>Opioid</topic><topic>Opioid Peptides - administration &amp; dosage</topic><topic>Opioid Peptides - pharmacology</topic><topic>Pain - drug therapy</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Reflex - drug effects</topic><topic>Regression Analysis</topic><topic>Sciatic Nerve - injuries</topic><topic>Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. 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These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>10323275</pmid><doi>10.1016/S0014-2999(99)00111-9</doi><tpages>6</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Animals
Antinociception
Biological and medical sciences
Carrageenan
Dose-Response Relationship, Drug
Excipients
Female
Fundamental and applied biological sciences. Psychology
Inflammation - chemically induced
Injections, Spinal
Muscle, Skeletal - drug effects
Nerve injury
Neuropathic pain
Nociceptin
Opioid
Opioid Peptides - administration & dosage
Opioid Peptides - pharmacology
Pain - drug therapy
Rats
Rats, Sprague-Dawley
Reflex - drug effects
Regression Analysis
Sciatic Nerve - injuries
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception)
interoception
electrolocation. Sensory receptors
Spinal cord
Spinal Cord - drug effects
Vertebrates: nervous system and sense organs
title Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section
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