Alterations in neuronal excitability and the potency of spinal mu, delta and kappa opioids after carrageenan-induced inflammation

Stanfa, Louise C.; Sullivan, Ann F.; Dickenson, Anthony H.

doi:10.1016/0304-3959(92)90040-i

Cited by 138 publications

(85 citation statements)

References 38 publications

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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: 77%

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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Section: Discussioncontrasting

confidence: 77%

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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“…Upregulation of its receptors results in decreased analgesia in some neuropathic models; decreased CCK concentrations, in inflammatory models, results in enhancement of mu receptor effects. 88 Alternatively, antagonists of the CCK receptor may enhance the analgesic action of opioids. 89,90 It has been shown that NMDA receptor activation results in formation of nitric oxide (NO).…”

Section: Nmda Receptor Antagonistsmentioning

confidence: 99%

Preemptive analgesia I: physiological pathways and pharmacological modalities

Kelly

Ahmad

Brull

2001

Can J Anesth/J Can Anesth

259

181

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P Pu ur rp po os se e: : This two-part review summarizes the current knowledge of physiological mechanisms, pharmacological modalities and controversial issues surrounding preemptive analgesia.S So ou ur rc ce e: : Articles from 1966 to present were obtained from the MEDLINE databases. Search terms included: analgesia, preemptive; neurotransmitters; pain, postoperative; hyperalgesia; sensitization, central nervous system; pathways, nociception; anesthetic techniques; analgesics, agents.P Pr ri in nc ci ip pa al l f fi in nd di in ng gs s: : The physiological basis of preemptive analgesia is complex and involves modification of the pain pathways. The pharmacological modalities available may modify the physiological responses at various levels. Effective preemptive analgesic techniques require multi-modal interception of nociceptive input, increasing threshold for nociception, and blocking or decreasing nociceptor receptor activation. Although the literature is controversial regarding the effectiveness of preemptive analgesia, some general recommendations can be helpful in guiding clinical care. Regional anesthesia induced prior to surgical trauma and continued well into the postoperative period is effective in attenuating peripheral and central sensitization. Pharmacologic agents such as NSAIDs (non-steroidal anti-inflammatory drugs) opioids, and NMDA (Nmethyl-D-aspartate) -and alpha-2-receptor antagonists, especially when used in combination, act synergistically to decrease postoperative pain.C Co on nc cl lu us si io on n: : The variable patient characteristics and timing of preemptive analgesia in relation to surgical noxious input requires individualization of the technique(s) chosen. Multi-modal analgesic techniques appear most effective.Objectif : La présente revue, en deux parties, résume les connaissances actuelles sur les mécanismes physiologiques et les modalités pharmacologiques de lanalgésie préventive ainsi que sur les questions controversées qui lentourent.Sources : Des articles, de 1966 à aujourdhui, obtenus à partir des bases de données MEDLINE. Les termes de la recherche compren-

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“…Similarly, the reduced effectiveness of opioids in neuropathic pain has been attributed to a decrease in spinal opioid receptors (Kohno et al, 2005) and to increased spinal CCK release. (Wiesenfeld-Hallin et al, 2002) Enhanced opioid analagesia during inflammation has been well established for peripherally (Stein et al, 2001), systemically (Kayser & Guilbaud, 1983;Joris et al, 1990) and spinally (Hylden et al, 1991;Stanfa et al, 1992) administered opioids. While i.t.…”

Section: Introductionmentioning

confidence: 99%

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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Alterations in neuronal excitability and the potency of spinal mu, delta and kappa opioids after carrageenan-induced inflammation

Cited by 138 publications

References 38 publications

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

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

Preemptive analgesia I: physiological pathways and pharmacological modalities

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

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