Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Stanfa, Louise C.; Dickenson, Anthony H.

doi:10.1111/j.1476-5381.1993.tb13493.x

Cited by 84 publications

(41 citation statements)

References 38 publications

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“…administration of a CCK-B antagonist was unable to enhance morphine analgesia in peripheral inflammatory conditions. Also, consistent with Stanfa & Dickenson (1993) who found that i.t. administration of CCK-8S attenuated the effects of morphine in animals with carrageenan inflammation (but not in normal animals), the present results show that a low dose of CCK-8S (1 ng) decreases morphine analgesia in LPS-treated rats, but not in naïve rats.…”

Section: Discussionsupporting

confidence: 88%

“…Although the CCK antagonist LY225910 was able to increase thermal latencies after morphine in naïve animals, it was unable to do so in LPStreated rats. The present results with CNS inflammation parallel those with peripheral inflammation, since a similar effect has been shown electrophysiologically in a model of peripheral carrageenan inflammation (Stanfa & Dickenson, 1993), and behaviourally in a model of visceral inflammation (Friedrich & Gebhart, 2000). Thus, i.t.…”

Section: Discussionsupporting

confidence: 86%

“…While i.t. administration of CCK attenuates morphine antinociception in the carrageenan model of peripheral inflammation, spinally administered CCK-B antagonists have little or no effect on opioid analgesia in this model (Stanfa & Dickenson, 1993), or in a model of visceral inflammmation (Friedrich & Gebhart, 2000). In neuropathic pain models, however, coadministration of morphine with a CCK-B antagonist is able to enhance morphine analgesia so that the analgesia is comparable to that seen in naïve animals (Nichols et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

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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 naïve 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 naıve animals. Further, spinal anti-NGF (3 mg) was able to reduce morphine analgesia in LPS-treated rats, but not in naïve animals, an effect that was reversed by spinal administration of LY-225910. 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 LPS animals as compared to controls, and this was reversed by anti-NGF pretreatment. Finally, chronic spinal administration of b-NGF (7 mg/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.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

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“…In the same study, morphine was found to be considerably more potent in the inflamed animal when compared to normal rats, suggesting that there appears to be a reduced availability of CCK in the spinal cord following carrageenan-inflammation (Stanfa et al, 1992;Stanfa & Dickenson, 1993). Both the failure of CCK antagonists to potentiate the action of morphine and the increased potency of morphine in the carrageenan inflammation model are in disagreement with the observations of the present study.…”

Section: Discussioncontrasting

confidence: 56%

“…cortex, thalamus, periaqueductal grey, medullary nuclei) and spinal cord associated with the control of nocicpetive information. In behavioural studies, CCK has been shown to modulate noxious stimuli in a complex manner with higher 'pharmacological' doses producing a naloxone-reversible antinociception (Barbaz et al, 1989;Hill et al, 1987b) whilst lower, more 'physiological' doses reverse the antinociception produced by exogenous, mainly morphine and endogenous opioids (Faris et al, 1983;Barbaz et al, 1989; endogenous CCK in the spinal cord and, consequently, CCKB antagonists appear no longer effective at modulating the morphine responses (Stanfa & Dickenson, 1993).…”

Section: Introductionmentioning

confidence: 99%

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Singh

Oles

Field

et al. 1996

British J Pharmacology

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1 The ability of a selective CCKA receptor antagonist PD 140548 and a selective CCKB receptor antagonist CI-988 (formerly PD 134308) to modulate the various in vivo properties of morphine was investigated in the rat. 2 PD 140548 dose-dependently (0.001 -1.0 mg kg-1, i.p.) antagonised the development of conditioned place preference to morphine (2.0 mg kg'-, s.c.). In contrast, CI-988 (0.01 -1.0 mg kg-', i.p.) did not affect this morphine-induced behaviour. Neither of the CCK receptor antagonists blocked or generalised to the morphine (3.0 mg kg-', i.p.) discriminative stimulus. 3 CI-988 (0.001-10.0 mg kg-', s.c.) at doses of 0.05 and 0.1 mg kg-' (s.c.), potentiated the antinociceptive action of a threshold dose of morphine (5.0 mg kg-', i.p.) in a radiant heat model of acute nociception, the rat tail flick test. Furthermore, at 0.01 mg kg-' it potentiated the antinociceptive action of morphine (3.0 mg kg-') during the acute phase of the rat paw formalin test. And at doses of 0.01 and 0.1 mg kg-' it also potentiated the antinociceptive action of morphine (1.0 mg kg-') during the tonic phase of the formalin test. However, in both models, higher doses of CI-988 were ineffective. In contrast, PD 140548 (0.001 -10 mg kg-', s.c.) was only active at a dose of 1.0 mg kg-1 (s.c.) and only in the tonic phase of the formalin test. Neither CI-988 nor PD 140548 possessed any intrinsic antinociceptive action in either of the tests. Chronic treatment with CI-988 (0.01 mg kg-', s.c.) prevented the development of tolerance to morphine antinociception (4 mg kg-', s.c.) following a 6 day period of twice daily injections of morphine escalating from 1 to 16 mg kg-' (i.p.). 4 Morphine dose-dependently (1-10 mg kg-', s.c.) reduced the distance travelled by a charcoal meal in the rat intestine. Neither PD 140548 (0.01 -1.0 mg kg-', i.p.) nor CI-988 (0.01 -1.0 mg kg-', i.p.) potentiated or suppressed this inhibitory action of morphine. 5 In conclusion, the results of the present study indicate that CCKA and CCKB receptors modulate different properties of morphine. Thus, whilst a selective CCKA receptor antagonist blocked the rewarding properties of morphine, a selective CCKB receptor antagonist potentiated the antinociceptive action. However, neither compound displayed a potential for modulating the influence of morphine on gastro-intestinal motility. It is suggested that these findings may have important implications for development of CCK receptor antagonists as analgesic adjuncts to the therapeutic use of morphine.

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Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

Asim,

Wang,

Waris

et al. 2024

BioFactors

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Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long‐term potentiation (iLTP) and excitatory long‐term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.

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Cholecystokinin as a factor in the enhanced potency of spinal morphine following carrageenin inflammation

Cited by 84 publications

References 38 publications

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

Effect of CCK receptor antagonists on the antinociceptive, reinforcing and gut motility properties of morphine

Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

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