The Effect of Peripherally Administered CDP-Choline in an Acute Inflammatory Pain Model: The Role of α7 Nicotinic Acetylcholine Receptor

Gurun, Mine Sibel; Parker, Renée; Eisenach, James C.; Vincler, Michelle

doi:10.1213/ane.0b013e31819dcd08

Cited by 54 publications

(33 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Peripheral (intraplantar) application of nicotinic agonists selective for the α4β2 or α7 subtype is antinociceptive [19,58,59]. Nicotinic receptors on peripheral terminals may contribute to these effects, although direct evidence for this is lacking.…”

Section: Neural Substrates For Nachr-dependent Analgesiamentioning

confidence: 99%

Neuronal nicotinic receptors as analgesic targets: It's a winding road

Umana

Daniele

McGehee

2013

Biochemical Pharmacology

View full text Add to dashboard Cite

Along with their well known role in nicotine addiction and autonomic physiology, neuronal nicotinic receptors (nAChRs) also have profound analgesic effects in animal models and humans. This is not a new idea, even in the early 1500s, soon after tobacco was introduced to the new world, its proponents listed pain relief among the beneficial properties of smoking. In recent years, analgesics that target specific nAChR subtypes have shown highly efficacious antinociceptive properties in acute and chronic pain models. To date, the side effects of these drugs have precluded their advancement to the clinic. This review summarizes the recent efforts to identify novel analgesics that target nAChRs, and outlines some of the key neural substrates that contribute to these physiological effects. There remain many unanswered mechanistic questions in this field, and there are still compelling reasons to explore neuronal nAChRs as targets for the relief of pain.

show abstract

Section: Neural Substrates For Nachr-dependent Analgesiamentioning

confidence: 99%

Neuronal nicotinic receptors as analgesic targets: It's a winding road

Umana

Daniele

McGehee

2013

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…These receptors are also present on immune and nonimmune cytokine-producing cells, including macrophages and keratinocytes (Wang and Wang, 2003;Pavlov and Tracey, 2004). Furthermore, a7 nAChR agonists, such as choline, CDP-choline, compound B, JN403 [(S)-(1-azabicyclo [2.2.2]oct-3-yl)-carbamic acid (S)-1-(2-fluoro-phenyl)-ethyl ester], and (2)-spiro[1-azabicyclo[2.2.2]octane-3,59-oxazolidin]-29-one (AR-R17779, exhibited anti-inflammatory effects in various inflammation and pain models in rodents (Damaj et al, 2000;Medhurst et al, 2008;Feuerbach et al, 2009;Gurun et al, 2009;van Maanen et al, 2009;Rowley et al, 2010;Marrero et al, 2011;Munro et al, 2012). Although a7 nAChR agonists showed beneficial effects in inflammatory animal models in some studies, these effects were not seen consistently in other studies (Gao et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The Antinociceptive Effects of Nicotinic Receptors α7-Positive Allosteric Modulators in Murine Acute and Tonic Pain Models

Freitas

Carroll

Damaj

2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The a7 nicotinic acetylcholine receptor (nAChR) subtype is abundantly expressed in the central nervous system and in the periphery. Recent evidence suggests that a7 nAChR subtypes, which can be activated by an endogenous cholinergic tone, comprising acetylcholine and the a7 nAChR agonist choline, play an important role in subchronic pain and inflammation. This study's objective was to test whether a7 nAChR positive allosteric modulators (PAMs) produce antinociception in in vivo mouse models of acute and persistent pain.nAChR PAMs in acute and persistent pain, we found that, although neither reduced acute thermal pain, only PNU-120596 dose-dependently attenuated paw-licking behavior in the formalin test. The long-acting effect of PNU-120596 in this test was in discordance with its pharmacokinetic profile in mice, which suggests the involvement of postreceptor signaling mechanisms. Our results with selective mitogen-activated protein kinase kinase inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene monoethanolate (U0126) argues for an important role of extracellular signal-regulated kinase-1/2 pathways activation in PNU-120596's antinociceptive effects. The a7 antagonist MLA, administered intrathecally, reversed PNU-120596's effects, confirming PNU-120596's action, in part, through central a7 nAChRs. Importantly, tolerance to PNU-120596 was not developed after subchronic treatment of the drug. Surprisingly, PNU-120596's antinociceptive effects were blocked by NS1738. Our results indicate that type II a7 nAChR PAM PNU-120596, but not type I a7 nAChR PAM NS1738, shows significant antinociception effects in persistent pain models in mice.

show abstract

“…These compounds enter the circulation and are taken up into the cells and utilized for intracellular enzymatic resynthesis of CDP-choline [6]; it has been shown that most of the effects of exogenously administered CDP-choline are mediated by its choline, and thereby acetylcholine (ACh), component [5,7]. We recently demonstrated that central and peripheral injection of CDP-choline induced dose-dependent and time-dependent antinociceptive effects in acute, inflammatory, and chronic constriction injury (CCI) models of neuropathic pain in rats without any motor impairment [8][9][10][11]. In addition, our previous studies showed that centrally administered CDP-choline elicited an analgesic effect through central cholinergic and opioidergic systems [8,9,11].…”

Section: Introductionmentioning

confidence: 99%

Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain

Bağdaş

Yucel-Ozboluk²,

Orhan³

et al. 2013

NeuroReport

View full text Add to dashboard Cite

Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect.

show abstract

The Effect of Peripherally Administered CDP-Choline in an Acute Inflammatory Pain Model: The Role of α7 Nicotinic Acetylcholine Receptor

Abstract: The results of this study suggest that intraplantar CDP-choline has antihypersensitivity and antiinflammatory effects mediated via alpha7nAChRs in the carrageenan-induced inflammatory pain model.

Cited by 54 publications

References 33 publications

Neuronal nicotinic receptors as analgesic targets: It's a winding road

Neuronal nicotinic receptors as analgesic targets: It's a winding road

The Antinociceptive Effects of Nicotinic Receptors α7-Positive Allosteric Modulators in Murine Acute and Tonic Pain Models

Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain

Contact Info

Product

Resources

About