Spinal effect of the cholecystokinin-B receptor antagonist CI-988 on hyperalgesia, allodynia and morphine-induced analgesia in diabetic and mononeuropathic rats

Coudoré-Civiale, Marie-Ange; Courteix, Christine; Fialip, J.; Boucher, Michel; Eschalier, Alain

doi:10.1016/s0304-3959(00)00304-3

Cited by 34 publications

(17 citation statements)

References 35 publications

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“…CCK-8 is considered to be the strongest endogenous anti-opioid substance [41,42]. At the level of whole-animal behavior or the electrical activities of central painrelated neurons, many data pointed out that CCK-8 can selectively antagonize the analgesic effect of EA or morphine [16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

L-364,718 Potentiates Electroacupuncture Analgesia Through Cck-A Receptor of Pain-Related Neurons in the Nucleus Parafascicularis

Shi

Yang

et al. 2010

Neurochem Res

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Electroacupuncture (EA) has been successfully used to alleviate pain produced by various noxious stimulus. Cholecystokinin-8 (CCK-8) is a neuropeptide involved in the mediation of pain. We have previously shown that CCK-8 could antagonize the analgesic effects of EA on pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the nucleus parafascicularis (nPf). However, its mechanism of action is not clear. In the present study, we applied behavioral and neuroelectrophysiological methods to determine whether the mechanisms of CCK-8 antagonism to EA analgesia are mediated through the CCK-A receptors of PENs and PINs in the nPf of rats. We found that focusing radiant heat on the tail of rats caused a simultaneous increase in the evoked discharge of PENs or a decrease in the evoked discharge of PINs in the nPf and the tail-flick reflex. This showed that radiant heat could induce pain. EA stimulation at the bilateral ST 36 acupoints in rats for 15 min resulted in an inhibition of the electrical activity of PEN, potentiation of the electrical activity of PIN, and prolongation in tail-flick latency (TFL), i.e. EA stimulation produced an analgesic effect. The analgesic effect of EA was antagonized when CCK-8 was injected into the intracerebral ventricle of rats. The antagonistic effect of CCK-8 on EA analgesia was reversed by an injection of CCK-A receptor antagonist L-364,718 (100 ng/μl) into the nPf of rats. Our results suggest that the pain-related neurons in the nPf have an important role in mediating EA analgesia. L-364,718 potentiates EA analgesia through the CCK-A receptor of PENs and PINs in the nPf.

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Section: Discussionmentioning

confidence: 99%

L-364,718 Potentiates Electroacupuncture Analgesia Through Cck-A Receptor of Pain-Related Neurons in the Nucleus Parafascicularis

Shi

Yang

et al. 2010

Neurochem Res

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“…Opioid treatment of neuropathic pain is often discouraged, because of concerns about ineffectiveness, the potential for the development of tolerance, the risk of addiction, and various side effects. Several clinical studies showed that opioids, particularly morphine, lacked potent analgesic efficacy in neuropathic pain in humans [203]. On the contrary, other studies showed that morphine could be effective in some patients suffering from neuropathic pain.…”

Section: Opioid Analgesia Clinical Studymentioning

confidence: 99%

Opioids in Neuropathic Pain

Przewłocki

Przewłocka

2005

CPD

108

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Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opioid specific signaling. Endogenous opioid systems were found to be represented in the regions involved in the nociception and are implicated in chronic pain. Opioid peptides biosynthesis and opioid receptors density in the nociceptive pathways and their functions change under various conditions associated with neuropathic pain following damage to the spinal cord and injury of peripheral nerves. Identification of a role of opioid systems in neuropathic pain and molecular and cellular mechanisms underlying these processes are of importance to understanding of the opioid action in neuropathic pain that will hopefully facilitate development of therapeutic strategies in which effectiveness of opioids in alleviation neuropathic pain is increased.

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“…In diabetic rats, CI-988 enhanced the analgesia induced by morphine, 214 and induced antinociceptive effects on mechanical hyperalgesia. 215 The lack of anxiolytic effects of CI-988 in humans has been attributed to its low bioavailability, 210,216 in part due to its high molecular weight. Therefore, to improve the pharmacokinetic profile, the structure of CI-988 was modified with the aim of reducing the molecular weight and improving the aqueous solubility and absorption, maintaining the binding potency and selectivity at CCK 2 receptors.…”

Section: G Dipeptoidsmentioning

confidence: 99%

Cholecystokinin antagonists: Pharmacological and therapeutic potential

Herranz

2003

Medicinal Research Reviews

168

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Cholecystokinin (CCK) is a regulatory peptide hormone, predominantly found in the gastrointestinal tract, and a neurotransmitter present throughout the nervous system. In the gastrointestinal system CCK regulates motility, pancreatic enzyme secretion, gastric emptying, and gastric acid secretion. In the nervous system CCK is involved in anxiogenesis, satiety, nociception, and memory and learning processes. Moreover, CCK interacts with other neurotransmitters in some areas of the CNS. The biological effects of CCK are mediated by two specific G protein coupled receptor subtypes, termed CCK(1) and CCK(2). Over the past fifteen years the search of CCK receptor ligands has evolved from the initial CCK structure derived peptides towards peptidomimetic or non-peptide agonists and antagonists with improved pharmacokinetic profile. This research has provided a broad assortment of potent and selective CCK(1) and CCK(2) antagonists of diverse chemical structure. These antagonists have been discovered through optimization programs of lead compounds which were designed based on the structures of the C-terminal tetrapeptide, CCK-4, or the non-peptide natural compound, asperlicin, or derived from random screening programs. This review covers the main pharmacological and therapeutic aspects of these CCK(1) and CCK(2) antagonist. CCK(1) antagonists might have therapeutic potential for the treatment of pancreatic disorders and as prokinetics for the treatment of gastroesophageal reflux disease, bowel disorders, and gastroparesis. On the other hand, CCK(2) antagonists might have application for the treatment of gastric acid secretion and anxiety disorders.

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Spinal effect of the cholecystokinin-B receptor antagonist CI-988 on hyperalgesia, allodynia and morphine-induced analgesia in diabetic and mononeuropathic rats

Cited by 34 publications

References 35 publications

L-364,718 Potentiates Electroacupuncture Analgesia Through Cck-A Receptor of Pain-Related Neurons in the Nucleus Parafascicularis

L-364,718 Potentiates Electroacupuncture Analgesia Through Cck-A Receptor of Pain-Related Neurons in the Nucleus Parafascicularis

Opioids in Neuropathic Pain

Cholecystokinin antagonists: Pharmacological and therapeutic potential

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