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

Singh, Lakhbir; Oles, Ryszard J.; Field, Mark; Atwal, Paldeep S.; Woodruff, G.N.; Hunter, John C.

doi:10.1111/j.1476-5381.1996.tb15539.x

Cited by 25 publications

(18 citation statements)

References 50 publications

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“…Blockade of the action of CCK, especial CCK B receptor, potentiates morphine-induced antinociception (Singh et al, 1996;McNally, 1999). However, our result clearly demonstrated that CCK was not involved in the EM-2-induced antianalgesia, which was evidenced by our finding that the pretreatment of antiserum against CCK could not restore morphine-induced antinociception.…”

Section: Em-2 At Subantinociceptive Doses Produces Antianalgesia Agaicontrasting

confidence: 55%

Dynorphinergic Mechanism Mediating Endomorphin-2-Induced Antianalgesia in the Mouse Spinal Cord

Sun²,

Darpolar³

et al. 2003

J Pharmacol Exp Ther

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We have previously demonstrated that both endomorphin-1 (EM-1) and endomorphin-2 (EM-2) at high doses (1.75-35 nmol) given intrathecally (i.t.) or intracerebroventricularly produce antinociception by stimulation of -opioid receptors. Now, we report that EM-2 at small doses (0.05-1.75 nmol), which injected alone did not produce antinociception, produces antianalgesia against opioid agonist-induced antinociception. The tail-flick (TF) response was used to test the antinociception in male CD-1 mice. Intrathecal pretreatment with EM-2 (0.02-1.75 nmol) 45 min before i.t. morphine (3.0 nmol) injection dose dependently attenuated morphine-induced TF inhibition. On the other hand, a similar dose of EM-1 (1.64 nmol) failed to produce any antianalgesic effect. The EM-2 (1.75 nmol)-produced anti-analgesia against morphine-induced TF inhibition was blocked by i.t. pretreatment with the -opioid antagonist naloxone or 3-methoxynaltrexone, but not ␦-opioid receptor antagonist naltrindole, -opioid receptor antagonist nor-binal- Endogenous opioid tetrapeptides endomorphin-1 (EM-1) and endomorphin-2 (EM-2) have been found to be highly selective for -opioid receptors (Zadina et al., 1997). Both EM-1 and EM-2 potently compete with -opioid receptor binding with no appreciable affinity with ␦-and -opioid receptors and selectively activate -opioid receptor-mediated G-proteins with [35 S]guanosine 5Ј-O-(3-thio)triphosphate binding (Goldberg et al., 1998;Narita et al., 1998Narita et al., , 2000Monory et al., 2000). The increases of the [ 35 S]guanosine 5Ј-O-(3-thio)triphosphate binding and antinociceptive effects induced by both EM-1 and EM-2 are selectively blocked by the pretreatment with selective -opioid receptor antagonist ␤-funaltrexamine or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH 2 , indicating that the effects are mediated by the stimulation of -opioid receptors.However, recent studies indicate that the antinociceptive effects induced by EM-1 and EM-2 are mediated by the stimulation of different subtypes of -opioid receptors. Pretreatment with -opioid receptor antagonist 3-methoxynaltrexone selectively attenuated EM-2-but not EM-1-induced antinociception, whereas ␤-funaltrexamine inhibits both (Sakurada et al., 2000). There is an asymmetric cross-tolerance between EM-1 and EM-2, where mice made acutely tolerant to EM-1 are not cross-tolerant to EM-2, but mice made acutely tolerant to EM-2 cause partial cross-tolerance to EM-1 (Wu et al., 2001). Intrathecal pretreatment with antisense oligodeoxynucleotides against exon-8 of -opioid receptor clone inhibits the antinociception induced by EM-1

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Section: Em-2 At Subantinociceptive Doses Produces Antianalgesia Agaicontrasting

confidence: 55%

Dynorphinergic Mechanism Mediating Endomorphin-2-Induced Antianalgesia in the Mouse Spinal Cord

Sun²,

Darpolar³

et al. 2003

J Pharmacol Exp Ther

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“…Animals were starved from food for 18 h prior to experiment, but were allowed free access to water. After 80 min of CS-HexFr or normal saline (SAL) administration, 2 ml of a 10% charcoal slurry in 5% powdered gum acacia was administered to each pigeon orally (Singh et al, 1996). For antagonism, MCP (30 mg/kg) or carbachol (0.1 mg/kg) was administered intramuscularly 5 min before drug administration.…”

Section: Gastrointestinal Motilitymentioning

confidence: 99%

Role of gastrointestinal motility/gastric emptying in cisplatin-induced vomiting in pigeon

Ullah

Subhan²,

Rauf³

et al. 2012

Afr. J. Pharm. Pharmacol.

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“…Indeed, numerous studies have demonstrated that the coadministration of CCK antagonists with morphine prevents the development of antinociceptive tolerance [162,180,181] . Furthermore, behavioral signs of already established antinociceptive tolerance to morphine have been reversed by CCK antiserum or CCKB antagonists at doses that did not enhance morphine antinociception in naive rats [167,[182][183][184] . Thus, these studies indicate that CCK has a pivotal role in mediating antinociceptive tolerance to opioids.…”

Section: Role Of Cck As An Endogenous Pronociceptive (Or 'Anti-opioidmentioning

confidence: 99%

Is Paradoxical Pain Induced by Sustained Opioid Exposure an Underlying Mechanism of Opioid Antinociceptive Tolerance?

et al. 2005

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Opiates are the primary treatment for pain management in cancer patients reporting moderate to severe pain, and are being increasingly used for non-cancer chronic pain. However, prolonged administration of opiates is associated with significant problems including the development of antinociceptive tolerance, wherein higher doses of the drug are required over time to elicit the same amount of analgesia. High doses of opiates result in serious side effects such as constipation, nausea, vomiting, dizziness, somnolence, and impairment of mental alertness. In addition, sustained exposure to morphine has been shown to result in paradoxical pain in regions unaffected by the initial pain complaint, and which may also result in dose escalation, i.e. ‘analgesic tolerance’. A concept that has been gaining considerable experimental validation is that prolonged use of opioids elicits paradoxical, abnormal pain. This enhanced pain state requires additional opioids to maintain a constant level of antinociception, and consequently may be interpreted as antinociceptive tolerance. Many substances have been shown to block or reverse antinociceptive tolerance. A non-inclusive list of examples of substances reported to block or reverse opioid antinociceptive tolerance include: substance P receptor (NK-1) antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists, nitric oxide (NO) synthase inhibitors, calcium channel blockers, cyclooxygenase (COX) inhibitors, protein kinase C inhibitors, competitive and non-competitive antagonists of the NMDA (N-methyl-D-aspartate) receptor, AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) antagonists, anti-dynorphin antiserum, and cholecystokinin (CCK) receptor antagonists. Without exception, these substances are also antagonists of pain-enhancing agents. Prolonged opiate administration indeed induces upregulation of substance P (SP) and calcitonin gene-related peptide (CGRP) within sensory fibers in vivo, and this is accompanied by an enhanced release of excitatory neurotransmitters and neuropeptides from primary afferent fibers upon stimulation. The enhanced evoked release of neuropeptides is correlated with the onset of abnormal pain states and opioid antinociceptive tolerance. Importantly, the descending pain modulatory pathway from the brainstem rostral ventromedial medulla (RVM) via the dorsolateral funiculus (DLF) is critical for maintaining the changes observed in the spinal cord, abnormal pain states and antinociceptive tolerance, because animals with lesion of the DLF did not show enhanced evoked neuropeptide release, or develop abnormal pain or antinociceptive tolerance upon sustained exposure to opiates. Microinjection of either lidocaine or a CCK antagonist into the RVM blocked both thermal and touch hypersensitivity as well as antinociceptive tolerance. Thus, prolonged opioid exposure enhances a descending pain facilitatory pathway from the RVM that is mediated at least in part by CCK activity and is essential for the maintenance of antinociceptive tolerance.

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

Cited by 25 publications

References 50 publications

Dynorphinergic Mechanism Mediating Endomorphin-2-Induced Antianalgesia in the Mouse Spinal Cord

Dynorphinergic Mechanism Mediating Endomorphin-2-Induced Antianalgesia in the Mouse Spinal Cord

Role of gastrointestinal motility/gastric emptying in cisplatin-induced vomiting in pigeon

Is Paradoxical Pain Induced by Sustained Opioid Exposure an Underlying Mechanism of Opioid Antinociceptive Tolerance?

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