Antinociceptive effects of choline against acute and inflammatory pain

Wang, Y.; Su, Dan‐Jie; Wang, R.-H.; Liu, Y.; Wang, H.

doi:10.1016/j.neuroscience.2004.12.026

Cited by 89 publications

(66 citation statements)

References 51 publications

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“…Results from in vitro experiments suggest that malignant growth can be halted with the use of snake neurotoxins (a-neurotoxins) or snail conotoxins (a-conotoxins) (75,76) because they are competitive antagonists of a7-nAChR (77). In vivo animal studies have further shown that a7-nAChR inhibitors, such as MLA (78,79) and a-Bgtx (80), can reverse the proangiogenic effects of nicotine and inhibit cancer cell growth (16,17,19,81,82). In a lung airway epithelial cell model (83), normal human bronchial epithelial (NHBE) cells were forced to transform by nicotinic activation of Akt, altering their growth characteristics.…”

Section: Nachr Antagonists As Potential Agents For Molecular Cancer Tmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

103

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The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and a-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that a9-nAChR is important for breast cancer formation, and in many in vivo studies, a9-nAChR-specific antagonists (e.g., a-ImI, a-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogeninduced breast cancer cell proliferation through inhibition of the a9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.

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Section: Nachr Antagonists As Potential Agents For Molecular Cancer Tmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

103

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“…nAChR a7 subtypes are characterized by their high calcium permeability and their rapid desensitization during agonist stimulation (Feuerbach et al, 2009) compared with other nAChR subtypes. In recent years, the a7 nAChR agonists were proposed as possible targets for cognitive enhancement, antinociception, and anti-inflammation properties (Damaj et al, 2000;Wang et al, 2005;de Jonge and Ulloa, 2007;Rowley et al, 2010;Thomsen et al, 2010). a7 nAChRs are present in supraspinal and spinal pain-transmission pathways (Gillberg and Aquilonius, 1985;Wada et al, 1989;Seguela et al, 1993;Khan et al, 1994;Cordero-Erausquin and Changeux, 2001;CorderoErausquin et al, 2004).…”

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

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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.

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“…The involvement of nicotinic acetylcholine receptors (nAChRs) in pain has been suggested by a number of experimental observations, and the administration of nAChR agonists reduces pain-related behaviors in several animal models (1)(2)(3)(4)(5). nAChRs are pentameric ligand-gated ion channels composed of ␣ (␣1-␣10) and non-␣ (␤1-␤4, , ␥, and ␦) subunits.…”

mentioning

confidence: 99%

Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors

Vincler

Wittenauer

Parker

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

213

264

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␣9␣10 nicotinic acetylcholine receptors (nAChRs) have been identified in a variety of tissues including lymphocytes and dorsal root ganglia; except in the case of the auditory system, the function of ␣9␣10 nAChRs is not known. Here we show that selective block (rather than stimulation) of ␣9␣10 nAChRs is analgesic in an animal model of nerve injury pain. In addition, blockade of this nAChR subtype reduces the number of choline acetyltransferase-positive cells, macrophages, and lymphocytes at the site of injury. Chronic neuropathic pain is estimated to affect up to 8% of the world's population; the numerous analgesic compounds currently available are largely ineffective and act through a small number of pharmacological mechanisms. Our findings not only suggest a molecular mechanism for the treatment of neuropathic pain but also demonstrate the involvement of ␣9␣10 nAChRs in the pathophysiology of peripheral nerve injury.N europathic pain is a prolonged, debilitating state characterized by allodynia (pain produced by previously innocuous stimuli), hyperalgesia (an increased or exaggerated response to painful stimuli), and spontaneous pain. Neuropathic pain is often refractory to conventional pain therapeutics such as opioids and nonsteroidal antiinflammatory agents and, therefore, represents a large, unmet clinical need. Neuropathic pain can be triggered in a variety of ways; injury to a peripheral nerve is one of the most common causes.The involvement of nicotinic acetylcholine receptors (nAChRs) in pain has been suggested by a number of experimental observations, and the administration of nAChR agonists reduces pain-related behaviors in several animal models (1-5). nAChRs are pentameric ligand-gated ion channels composed of ␣ (␣1-␣10) and non-␣ (␤1-␤4, , ␥, and ␦) subunits. The ␣2-␣6 and ␤2-␤4 subunits form heteromeric channels consisting of a combination of ␣ and ␤ subunits (6). Homomeric channels can be formed by ␣7 or ␣9 subunits; the ␣10 subunit will only form functional receptors when it is expressed with the ␣9 subunit (6). Many of the nAChRs show widespread patterns of neuronal and nonneuronal distribution; ␣9 and/or ␣10 subunits have been reported within hair cells of the inner ear (7), sperm (8), dorsal root ganglion neurons (9), skin keratinocytes (10), the pars tuberalis of the pituitary (11), and lymphocytes (12). The function of ␣9␣10 nAChRs in the auditory system has been well characterized (13), but little is known regarding the function of ␣9␣10 nAChRs in other tissues. Here we demonstrate that the highly selective antagonist of ␣9␣10 nAChRs, RgIA, is analgesic and reduces migration of macrophages, lymphocytes, and acetylcholine (ACh)-producing cells into the area of nerve injury. ResultsRgIA Is Antinociceptive. Chronic constriction injury (CCI) produced mechanical hypersensitivity within 7 days of sciatic nerve ligation (Fig. 1). Paw withdrawal thresholds (PWTs) were reduced from 122 Ϯ 5 g to 26 Ϯ 5 g 7 days after CCI. The i.m. administration of the ␣9␣10-selective Conus peptide, RgIA, increased...

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Antinociceptive effects of choline against acute and inflammatory pain

Cited by 89 publications

References 51 publications

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

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

Molecular mechanism for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors

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