{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:53:26Z","timestamp":1773730406463,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T00:00:00Z","timestamp":1582502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["10\/IN.1\/B2976"],"award-info":[{"award-number":["10\/IN.1\/B2976"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPAR\u03b1, PPAR\u03b2\/\u03b4, PPAR\u03b3) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPAR\u03b1 (GW6471), PPAR\u03b2\/\u03b4 (GSK0660) or PPAR\u03b3 (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPAR\u03b1 and PPAR\u03b2\/\u03b4 antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPAR\u03b3 antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPAR\u03b1 and PPAR\u03b2\/\u03b4 in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPAR\u03b3 potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone.<\/jats:p>","DOI":"10.3390\/molecules25041007","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T05:44:12Z","timestamp":1582695852000},"page":"1007","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone"],"prefix":"10.3390","volume":"25","author":[{"given":"Jessica C.","family":"Gaspar","sequence":"first","affiliation":[{"name":"Pharmacology and Therapeutics Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bright N.","family":"Okine","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Llorente-Berzal","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Roche","sequence":"additional","affiliation":[{"name":"Galway Neuroscience Centre, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Centre for Pain Research, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Physiology Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-621X","authenticated-orcid":false,"given":"David P.","family":"Finn","sequence":"additional","affiliation":[{"name":"Pharmacology and Therapeutics Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Galway Neuroscience Centre, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"},{"name":"Physiology Department, National University of Ireland Galway, University Road, H91 W5P7 Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/347645a0","article-title":"Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators","volume":"347","author":"Issemann","year":"1990","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuroscience.2003.08.064","article-title":"Immunolocalization of peroxisome proliferator-activated receptors and retinoid x receptors in the adult rat CNS","volume":"123","author":"Moreno","year":"2004","journal-title":"Neuroscience"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejphar.2015.11.004","article-title":"Fatty acids, eicosanoids and PPAR gamma","volume":"785","author":"Savoye","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1038\/emboj.2010.197","article-title":"The nuclear receptor PPAR\u03b3 individually responds to serotonin- and fatty acid-metabolites","volume":"29","author":"Waku","year":"2010","journal-title":"EMBO J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ejphar.2005.05.032","article-title":"Anandamide induced PPAR\u03b3 transcriptional activation and 3T3-L1 preadipocyte differentiation","volume":"517","author":"Bouaboula","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1124\/mol.105.019117","article-title":"Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator activated receptor independently of cannabinoid receptors 1 and 2","volume":"70","author":"Rockwell","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/j.lfs.2005.05.012","article-title":"The search for the palmitoylethanolamide receptor","volume":"77","author":"LoVerme","year":"2005","journal-title":"Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature01921","article-title":"Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-a","volume":"425","author":"Fu","year":"2003","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hong, F., Xu, P., and Zhai, Y. (2018). The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082189"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s11883-001-0015-x","article-title":"The role of fibric acids in atherosclerosis","volume":"3","author":"Fruchart","year":"2001","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1111\/bph.14339","article-title":"PPARs and pain","volume":"176","author":"Okine","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12611","DOI":"10.1523\/JNEUROSCI.4127-15.2016","article-title":"Genetic Deletion of Neuronal PPAR\u03b3 Enhances the Emotional Response to Acute Stress and Exacerbates Anxiety: An Effect Reversed by Rescue of Amygdala PPAR\u03b3 Function","volume":"36","author":"Domi","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.pbb.2012.08.018","article-title":"Involvement of nitric oxide in pioglitazone memory improvement in morphine-induced memory impaired mice","volume":"103","author":"Babaei","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1101\/lm.1145209","article-title":"Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR- nuclear receptors","volume":"16","author":"Mazzola","year":"2009","journal-title":"Learn. Mem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/sj.npp.1301224","article-title":"Inhibition of Fatty-Acid Amide Hydrolase Accelerates Acquisition and Extinction Rates in a Spatial Memory Task","volume":"32","author":"Varvel","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1111\/bph.12540","article-title":"A role for PPAR\u03b1 in the medial prefrontal cortex in formalin-evoked nociceptive responding in rats","volume":"171","author":"Okine","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27618","DOI":"10.1038\/srep27618","article-title":"Localization of PPAR isotypes in the adult mouse and human brain","volume":"6","author":"Warden","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.brainres.2016.11.022","article-title":"Characterisation of peroxisome proliferator-activated receptor signalling in the midbrain periaqueductal grey of rats genetically prone to heightened stress, negative affect and hyperalgesia","volume":"1657","author":"Okine","year":"2017","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejphar.2009.04.022","article-title":"Central administration of palmitoylethanolamide reduces hyperalgesia in mice via inhibition of NF-\u03baB nuclear signalling in dorsal root ganglia","volume":"613","author":"Russo","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1254\/jphs.08207FP","article-title":"Pioglitazone Attenuates Tactile Allodynia and Thermal Hyperalgesia in Mice Subjected to Peripheral Nerve Injury. J. Pharmacol. Sci","volume":"108","author":"Maeda","year":"2008","journal-title":"J. Pharmacol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1124\/jpet.106.111385","article-title":"Rapid broad-spectrum analgesia through activation of peroxisome proliferator-activated receptor-alpha","volume":"319","author":"LoVerme","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4103\/0253-7613.111944","article-title":"Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-\u03b2\/\u03b4 receptors","volume":"45","author":"Gill","year":"2013","journal-title":"Indian J. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/AJP.0000000000000515","article-title":"Combination Drug Therapy of Pioglitazone and D-cycloserine Attenuates Chronic Orofacial Neuropathic Pain and Anxiety by Improving Mitochondrial Function Following Trigeminal Nerve Injury","volume":"34","author":"Lyons","year":"2017","journal-title":"Clin. J. Pain"},{"key":"ref_24","first-page":"194","article-title":"Pharmacological evidence for systemic and peripheral antinociceptive activities of pioglitazone in the rat formalin test: Role of PPAR\u03b3 and nitric oxide","volume":"561","author":"Mansouri","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ejphar.2006.12.026","article-title":"Antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPAR alpha, and pioglitazone, an agonist of PPAR gamma","volume":"561","author":"Oliveira","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1097\/j.pain.0000000000000687","article-title":"N-palmitoylethanolamide in the anterior cingulate cortex attenuates inflammatory pain behaviour indirectly via a CB1 receptor-mediated mechanism","volume":"157","author":"Okine","year":"2016","journal-title":"Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13041-015-0139-5","article-title":"Palmitoylethanolamide reduces pain-related behaviors and restores glutamatergic synapses homeostasis in the medial prefrontal cortex of neuropathic mice","volume":"8","author":"Guida","year":"2015","journal-title":"Mol. Brain"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.pain.2007.03.008","article-title":"Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain","volume":"133","author":"Goicoechea","year":"2007","journal-title":"Pain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1515\/znc-2006-7-803","article-title":"In vivo Analgesic and Anti-Inflammatory Activities of Ursolic Acid and Oleanoic Acid from Miconia albicans (Melastomataceae)","volume":"61","author":"Vasconcelos","year":"2006","journal-title":"Zeitschrift f\u00fcr Naturforsch. C"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.pneurobio.2009.04.003","article-title":"Stress-induced analgesia","volume":"88","author":"Butler","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1111\/j.1476-5381.2011.01478.x","article-title":"The endocannabinoid system in the rat dorsolateral periaqueductal grey mediates fear-conditioned analgesia and controls fear expression in the presence of nociceptive tone","volume":"165","author":"Olango","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.pain.2012.12.021","article-title":"Evidence for a role of GABAergic and glutamatergic signalling in the basolateral amygdala in endocannabinoid-mediated fear-conditioned analgesia in rats","volume":"154","author":"Rea","year":"2013","journal-title":"Pain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1177\/070674370204701004","article-title":"PTSD and the Experience of Pain: Research and Clinical Implications of Shared Vulnerability and Mutual Maintenance Models","volume":"47","author":"Asmundson","year":"2002","journal-title":"Can. J. Psychiatry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"96","DOI":"10.11606\/S1518-8787.2017051007025","article-title":"Prevalence and clinical profile of chronic pain and its association with mental disorders","volume":"51","author":"Pereira","year":"2017","journal-title":"Rev. Saude Publica"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1139\/cjpp-2015-0242","article-title":"Pioglitazone and exenatide enhance cognition and downregulate hippocampal beta amyloid oligomer and microglia expression in insulin-resistant rats","volume":"94","author":"Gad","year":"2016","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.neurobiolaging.2014.09.028","article-title":"Central activation of PPAR-gamma ameliorates diabetes induced cognitive dysfunction and improves BDNF expression","volume":"36","author":"Kariharan","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_37","first-page":"138","article-title":"Suppression of nitric oxide synthesis by L-NAME reverses the beneficial effects of pioglitazone on scopolamine-induced memory impairment in mice","volume":"231","author":"Allami","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.pbb.2014.09.019","article-title":"NMDA receptors interact with the retrieval memory enhancing effect of pioglitazone in mice","volume":"126","author":"Gharedaghi","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1007\/s11064-016-2002-1","article-title":"WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice","volume":"41","author":"Xu","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.neulet.2017.04.052","article-title":"Pioglitazone improves the ability of learning and memory via activating ERK1\/2 signaling pathway in the hippocampus of T2DM rats","volume":"651","author":"Gao","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"376","DOI":"10.3389\/fphar.2018.00376","article-title":"Octadecylpropyl Sulfamide Reduces Neurodegeneration and Restores the Memory Deficits Induced by Hypoxia-Ischemia in Mice","volume":"9","author":"Kossatz","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/aps.2013.11","article-title":"Pioglitazone ameliorates memory deficits in streptozotocin-induced diabetic mice by reducing brain \u03b2-amyloid through PPAR\u03b3 activation","volume":"34","author":"Liu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1016\/j.lfs.2006.07.018","article-title":"Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats","volume":"79","author":"Pathan","year":"2006","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8027","DOI":"10.1073\/pnas.0903038106","article-title":"Fat-induced satiety factor oleoylethanolamide enhances memory consolidation","volume":"106","author":"Campolongo","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1124\/jpet.105.095059","article-title":"Fatty Acid Amide Hydrolase (\/) Mice Exhibit an Increased Sensitivity to the Disruptive Effects of Anandamide or Oleamide in a Working Memory Water Maze Task","volume":"317","author":"Varvel","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1097\/00001756-200410050-00023","article-title":"Rosiglitazone improves contextual fear conditioning in aged rats","volume":"15","author":"Gemma","year":"2004","journal-title":"Neuroreport"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17321","DOI":"10.1523\/JNEUROSCI.1569-12.2012","article-title":"PPAR \/RXR -Induced and CD36-Mediated Microglial Amyloid- Phagocytosis Results in Cognitive Improvement in Amyloid Precursor Protein\/Presenilin 1 Mice","volume":"32","author":"Yamanaka","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.biopha.2018.11.039","article-title":"Beta-caryophyllene alleviates diet-induced neurobehavioral changes in rats: The role of CB2 and PPAR-\u03b3 receptors","volume":"110","author":"Youssef","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.brainresbull.2018.08.015","article-title":"Chronic minocycline treatment reduces the anxiety-like behaviors induced by repeated restraint stress through modulating neuroinflammation","volume":"143","author":"Liu","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.expneurol.2017.06.014","article-title":"The interaction between alpha 7 nicotinic acetylcholine receptor and nuclear peroxisome proliferator-activated receptor-\u03b1 represents a new antinociceptive signaling pathway in mice","volume":"295","author":"Donvito","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1023\/A:1015500531113","article-title":"Peroxisome Proliferator-Activated Receptor Agonists Inhibit Inflammatory Edema and Hyperalgesia","volume":"26","author":"Taylor","year":"2002","journal-title":"Inflammation"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1017\/S1461145713000618","article-title":"Differential effects of acute and repeated stress on hippocampus and amygdala inputs to the nucleus accumbens shell","volume":"16","author":"Gill","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.jpain.2009.04.019","article-title":"Alterations in Extracellular Levels of Gamma-Aminobutyric Acid in the Rat Basolateral Amygdala and Periaqueductal Gray During Conditioned Fear, Persistent Pain and Fear-Conditioned Analgesia","volume":"10","author":"Rea","year":"2009","journal-title":"J. Pain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.jpain.2010.12.010","article-title":"Modulation of conditioned fear, fear-conditioned analgesia, and brain regional c-Fos expression following administration of muscimol into the rat basolateral amygdala","volume":"12","author":"Rea","year":"2011","journal-title":"J Pain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1111\/j.1460-9568.2007.05861.x","article-title":"The effect of CB1 receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats","volume":"26","author":"Roche","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00213-003-1629-1","article-title":"Cannabinoids modulate ultrasound-induced aversive responses in rats","volume":"172","author":"Finn","year":"2004","journal-title":"Psychopharmacology (Berl)."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e1419","DOI":"10.1038\/cddis.2014.376","article-title":"Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer\u2019s disease","volume":"5","author":"Scuderi","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/01902148.2013.879497","article-title":"Protective role of peroxisome proliferator-activated receptor-beta\/delta against pulmonary oxygen toxicity mediated through changes in NOS expression levels","volume":"40","author":"Bao","year":"2014","journal-title":"Exp. Lung Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1742-2094-10-20","article-title":"Molecular evidence for the involvement of PPAR-delta and PPAR-gamma in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma","volume":"10","author":"Paterniti","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1097\/01.j.pain.0000460333.79127.be","article-title":"Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPAR\u03b3 mechanisms","volume":"156","author":"Griggs","year":"2015","journal-title":"Pain"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.neuropharm.2013.01.020","article-title":"PPAR\u03b3 activation blocks development and reduces established neuropathic pain in rats","volume":"70","author":"Morgenweck","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.pain.2008.10.002","article-title":"Endocannabinoid-mediated enhancement of fear-conditioned analgesia in rats: Opioid receptor dependency and molecular correlates","volume":"140","author":"Butler","year":"2008","journal-title":"Pain"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1111\/bph.14376","article-title":"The prefrontal cortical endocannabinoid system modulates fear-pain interactions in a subregion-specific manner","volume":"176","author":"Rea","year":"2019","journal-title":"Br. J. 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