NDLI: The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of 7 Nicotinic Acetylcholine Receptors in Mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bagdas, Deniz Targowska-Duda, Katarzyna M. López, Jhon J. Perez, Edwin G. Arias, Hugo R. Damaj, M. Imad
Description	Author Affiliation: Bagdas D ( From the *Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia)
Abstract	BACKGROUND: Positive allosteric modulators (PAMs) facilitate endogenous neurotransmission and/or enhance the efficacy of agonists without directly acting on the orthosteric binding sites. In this regard, selective 7 nicotinic acetylcholine receptor type II PAMs display antinociceptive activity in rodent chronic inflammatory and neuropathic pain models. This study investigates whether 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2), a new putative 7-selective type II PAM, attenuates experimental inflammatory and neuropathic pains in mice. METHODS: We tested the activity of PAM-2 after intraperitoneal administration in 3 pain assays: the carrageenan-induced inflammatory pain, the complete Freund adjuvant-induced inflammatory pain, and the chronic constriction injury-induced neuropathic pain in mice. We also tested whether PAM-2 enhanced the effects of the selective 7 agonist choline in the mouse carrageenan test given intrathecally. Because the experience of pain has both sensory and affective dimensions, we also evaluated the effects of PAM-2 on acetic acid-induced aversion by using the conditioned place aversion test. RESULTS: We observed that systemic administration of PAM-2 significantly reversed mechanical allodynia and thermal hyperalgesia in inflammatory and neuropathic pain models in a dose- and time-dependent manner without motor impairment. In addition, by attenuating the paw edema in inflammatory models, PAM-2 showed antiinflammatory properties. The antinociceptive effect of PAM-2 was inhibited by the selective competitive antagonist methyllycaconitine, indicating that the effect is mediated by 7 nicotinic acetylcholine receptors. Furthermore, PAM-2 enhanced the antiallodynic and antiinflammatory effects of choline, a selective 7 agonist, in the mouse carrageenan test. PAM-2 was also effective in reducing acetic acid-induced aversion in the conditioned place aversion assay. CONCLUSIONS: These findings suggest that the administration of PAM-2, a new 7-selective type II PAM, reduces the neuropathic and inflammatory pain sensory and affective behaviors in the mouse. Thus, this drug may have therapeutic applications in the treatment and management of chronic pain.
File Format	HTM / HTML
ISSN	00032999
e-ISSN	15267598
DOI	10.1213/ANE.0000000000000902
Journal	Anesthesia & Analgesia
Issue Number	5
Volume Number	121
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2015-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Anesthesiology Acrylamides Therapeutic Use Analgesics Anti-inflammatory Agents Furans Pain Drug Therapy Alpha7 Nicotinic Acetylcholine Receptor Agonists Physiology Pharmacology Allosteric Regulation Drug Effects Animals Mice Mice, Inbred Icr Pathology Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Anesthesiology and Pain Medicine

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The Antinociceptive and Antiinflammatory Properties of 3-furan-2-yl-N-p-tolyl-acrylamide, a Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors in Mice

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