The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation
2009 (English)In: NEUROPHARMACOLOGY, ISSN 0028-3908, Vol. 56, no 3, 684-691 p.Article in journal (Refereed) Published
Animal models of inflammatory pain are characterized by the release of inflammatory mediators such as cytokines and neurotrophic factors, and enhanced analgesic sensitivity to opioids. In this study, we examine the mechanisms underlying this effect, in particular the roles of cholecystokinin (CCK) and nerve growth factor (NGF), in an animal model of central nervous system (CNS) inflammation induced by spinal administration of lipopolysaccharide (LPS). Although spinal administration of LY-225910 (25 ng), a CCK-B antagonist, enhanced morphine analgesia in naive rats, it was unable to do so in LPS-treated animals. Conversely, spinal CCK-8S administration (1 ng) decreased morphine analgesia in LPS-treated rats, but not in naive animals. Further, spinal anti-NGF (3 mu g) was able to reduce morphine analgesia in LPS-treated rats, but not in naive animals, an effect that was reversed by spinal administration of LY225910. While CCK-8S concentration was increased in spinal cord extracts of LPS animals as compared to controls, morphine-induced spinal CCK release in the extracellular space, as measured by in-vivo spinal cord microdialysis was inhibited in LIPS animals as compared to controls, and this was reversed by anti-NGF pretreatment. Finally, chronic spinal administration of beta-NGF (7 mu g/day) for 7 days enhanced spinal morphine analgesia, possibly by mimicking a CNS inflammatory state. We suggest that in intrathecally LPS-treated rats, spinal CCK release is altered resulting in enhanced morphine analgesia, and that this mechanism may be regulated to an important extent by NGF.
Place, publisher, year, edition, pages
2009. Vol. 56, no 3, 684-691 p.
CNS inflammation, Lipopolysaccharide, Thermal hyperalgesia, Nerve growth factor, Cholecystokinin, In-vivo microdialysis, Spinal cord
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-17279DOI: 10.1016/j.neuropharm.2008.12.002OAI: oai:DiVA.org:liu-17279DiVA: diva2:208132