Show simple item record

dc.contributor.advisorPorreca, Franken_US
dc.contributor.authorKovelowski, Carl Joseph
dc.creatorKovelowski, Carl Josephen_US
dc.date.accessioned2013-04-25T09:57:13Z
dc.date.available2013-04-25T09:57:13Z
dc.date.issued1999en_US
dc.identifier.urihttp://hdl.handle.net/10150/284132
dc.description.abstractThe central objective of this dissertation focuses on the influence of supraspinal descending nociceptive inhibitory and facilitatory systems in the modulation of both nociceptive input and neuropathic pain states due to peripheral nerve injury. Opioid delta-mediated antinociception within the RVM was observed to modulate supraspinally organized nociceptive behavior to acute stimuli. Spinally organized nociceptive behavior was observed to be δ-mediated as well, but appeared to be stimulus intensity dependent. In addition, activation of δ-opioid receptors within the RVM elicited a dose-dependent antinociceptive effect to tonic forms of nociceptive input. Lesioning of the dorsal lateral funiculus (DLF) was observed to block both the antinociceptive effect of δ-opioid receptor activation in the RVM and attenuation of FLI in the lumbar spinal cord. Finally, concurrent administration of delta-opioid receptor selective agonists into the RVM and intrathecally elicited a synergistic antinociceptive effect to acute forms of nociceptive stimuli. Taken together, these studies presented in this dissertation suggest that activation of δ-opioid receptors within the RVM elicits an antinociceptive effect to both acute and tonic forms of nociceptive input by way of a descending nociceptive inhibitory pathway localized within the DLF. Increased levels, or activity, of supraspinal CCK may consequent to tonic activation of an on-cell descending nociceptive facilitatory system and the behavioral signs of neuropathic pain. For example, CCK levels in the caudal brainstem, when quantified by protein immunoassay, were higher in those animals that had received a ligation to the L5/L6 spinal nerves in comparison to sham operated animals. Administration of the CCK(B) receptor antagonist L365,260 into the RVM was observed to reverse both tactile allodynia and thermal hyperalgesia in L5/L6 ligated animals. In addition, administration of CCK-8 sulfate into the RVM was observed to produce tactile allodynia as well as thermal hyperalgesia, but to a lesser extent, in otherwise normal animals. Finally, a loss of morphine efficacy, when administered into the PAG, was restored by the administration of L365,260 into the RVM of L₅/L₆ ligated animals. Taken together, these studies presented in this dissertation suggest the involvement of a supraspinal descending nociceptive facilitatory influence in the modulation of neuropathic pain due to peripheral nerve injury.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectBiology, Neuroscience.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectHealth Sciences, Medicine and Surgery.en_US
dc.titleSupraspinal opioid delta receptor mediated antinociception: Supraspinal modulation of neuropathic painen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest9965936en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology & Toxicologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b40485742en_US
refterms.dateFOA2018-05-18T06:27:10Z
html.description.abstractThe central objective of this dissertation focuses on the influence of supraspinal descending nociceptive inhibitory and facilitatory systems in the modulation of both nociceptive input and neuropathic pain states due to peripheral nerve injury. Opioid delta-mediated antinociception within the RVM was observed to modulate supraspinally organized nociceptive behavior to acute stimuli. Spinally organized nociceptive behavior was observed to be δ-mediated as well, but appeared to be stimulus intensity dependent. In addition, activation of δ-opioid receptors within the RVM elicited a dose-dependent antinociceptive effect to tonic forms of nociceptive input. Lesioning of the dorsal lateral funiculus (DLF) was observed to block both the antinociceptive effect of δ-opioid receptor activation in the RVM and attenuation of FLI in the lumbar spinal cord. Finally, concurrent administration of delta-opioid receptor selective agonists into the RVM and intrathecally elicited a synergistic antinociceptive effect to acute forms of nociceptive stimuli. Taken together, these studies presented in this dissertation suggest that activation of δ-opioid receptors within the RVM elicits an antinociceptive effect to both acute and tonic forms of nociceptive input by way of a descending nociceptive inhibitory pathway localized within the DLF. Increased levels, or activity, of supraspinal CCK may consequent to tonic activation of an on-cell descending nociceptive facilitatory system and the behavioral signs of neuropathic pain. For example, CCK levels in the caudal brainstem, when quantified by protein immunoassay, were higher in those animals that had received a ligation to the L5/L6 spinal nerves in comparison to sham operated animals. Administration of the CCK(B) receptor antagonist L365,260 into the RVM was observed to reverse both tactile allodynia and thermal hyperalgesia in L5/L6 ligated animals. In addition, administration of CCK-8 sulfate into the RVM was observed to produce tactile allodynia as well as thermal hyperalgesia, but to a lesser extent, in otherwise normal animals. Finally, a loss of morphine efficacy, when administered into the PAG, was restored by the administration of L365,260 into the RVM of L₅/L₆ ligated animals. Taken together, these studies presented in this dissertation suggest the involvement of a supraspinal descending nociceptive facilitatory influence in the modulation of neuropathic pain due to peripheral nerve injury.


Files in this item

Thumbnail
Name:
azu_td_9965936_sip1_m.pdf
Size:
2.849Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record