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Scientific References

The following scientific references support the safety and efficacy of PCQ Pet:

1.     Abramo, F., Campora, L., Albanese, F., Federica, M., Cristino, L., Petrosino, S., … Miragliotta, V. (2014). Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis. BMC Veterinary Research 2014, 10(21), 1–10. https://doi.org/10.1186/1746-6148-10-21

2.     Agah, S., Kim, H., Mertens-Talcott, S. U., & Awika, J. M. (2017). Complementary cereals and legumes for health: Synergistic interaction of sorghum flavones and cowpea flavonols against LPS-induced inflammation in colonic myofibroblasts. Molecular Nutrition and Food Research, 61(7), 1–11. https://doi.org/10.1002/mnfr.201600625

3.     Aggarwal B.B., Harikumar K.B. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol. 2009;41:40–59. doi: 10.1016/j.biocel.2008.06.010.      [CrossRef] 

4.     Aggarwal B.B., Kumar A., Bharti A.C. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003;23:363–398.   

5.     Aggarwal BB, Harikumar KB: Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009;41:40–59      

6.     Ahmad A, Crupi R, Impellizzeri D, Campolo M, Marino A, Esposito E, et al. Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice. Brain Behav Immun 2012; 26: 1310–21.   

7.     Ahn K, Smith SE, Liimatta MB, Beidler D, Sadagopan N, Dudley DT, et al. Mechanistic and pharmacological characterization of PF-04457845: a highly potent and selective fatty acid amide hydrolase inhibitor that reduces inflammatory and noninflammatory pain. J Pharmacol Exp Ther. 2011;338(1):114–124. doi: 10.1124/jpet.111.180257.      [CrossRef] 

8.     Alhouayek M, Muccioli GG. Harnessing the anti‐inflammatory potential of palmitoylethanolamide. Drug Discov Today 2014; 19: 1632–9.   

9.     Alhouayek, M., Bottemanne, P., Makriyannis, A., & Muccioli, G. G. (2017). N-acylethanolamine-hydrolyzing acid amidase and fatty acid amide hydrolase inhibition differentially affect N-acylethanolamine levels and macrophage activation. Biochimica et Biophysica Acta, 1862(5), 474–484. https://doi.org/10.1016/j.bbalip.2017.01.001

10.  Alhouayek, M., Bottemanne, P., Subramanian, K. V., Lambert, D. M., Makriyannis, A., Cani, P. D., & Muccioli, G. G. (2015). OK N-acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. FASEB Journal, 29(2), 650–661. https://doi.org/10.1096/fj.14-255208

11.  Allegri P., Mastromarino A., Neri P. Management of chronic anterior uveitis relapses: Efficacy of oral phospholipidic curcumin treatment. Long-term follow-up. Clin. Ophthalmol. 2010;4:1201–1206. doi: 10.2147/OPTH.S13271.      [CrossRef] 

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13.  Aloe L, Leon A, Levi‐Montalcini R. A proposed autacoid mechanism controlling mastocyte behaviour. Agents Actions 1993; 39: C145–7.   

14.  Alves, J. C., Santos, A. M., & Jorge, P. I. (2017). Effect of an Oral Joint Supplement When Compared to Carprofen in the Management of Hip Osteoarthritis in Working Dogs. Topics in Companion Animal Medicine, 32(4), 126–129. https://doi.org/10.1053/j.tcam.2017.10.003

15.  Andresen SR, Bing J, Hansen RM, Biering‐Sørensen F, Johannesen IL, Hagen EM, et al.Ultramicronized palmitoylethanolamide in spinal cord injury neuropathic pain: A randomized, double‐blind, placebo‐controlled trial. Pain 2016; doi: 10.1097/j.pain.0000000000000623   

16.  Artamonov M, Zhukov O, Shuba I, Storozhuk L, Khmel T, Klimashevsky V, et al. Incorporation of labelled N‐acylethanolamine (NAE) into rat brain regions in vivo and adaptive properties of saturated NAE under x‐ray irradiation. Ukr Biokhim Zh 2005; 77: 51–62.   

17.  Aulton ME. Aulton's Pharmaceutics. The Design and Manufacture of Medicines, 32nd edn. London: Churchill Livingstone, 2006. 

18.  Bacci C, Cassetta G, Emanuele B, Berengo M. Randomized split‐mouth study on postoperative effects of palmitoylethanolamide for impacted lower third molar surgery. ISRN Surg 2011; 2011: 917350.      

19.  Bang JS, Oh DH, Choi HM, Sur BJ, Lim SJ, Kim JY, et al. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1beta-stimulated fibroblast-like synoviocytes and in rat arthritis models. Arthritis Res Ther. 2009;11(2):R49. doi: 10.1186/ar2662.      [CrossRef] 

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23.  Borghi SM, Pinho-Ribeiro FA, Fattori V, Bussmann AJ, Vignoli JA, Camilios-Neto D, et al. Quercetin inhibits peripheral and spinal cord nociceptive mechanisms to reduce intense acute swimming-induced muscle pain in mice. PLoS One. 2016;11(9):e0162267. doi: 10.1371/journal.pone.0162267.     [CrossRef] 

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25.  Britti, D., Crupi, R., Impellizzeri, D., Gugliandolo, E., Fusco, R., Schievano, C., … Cuzzocrea, S. (2017). A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models. BMC Veterinary Research, 13(1), 229. https://doi.org/10.1186/s12917-017-1151-z

26.  Brown, D. C., Boston, R. C., & Farrar, J. T. (2013). Comparison of Force Plate Gait Analysis and Owner Assessment of Pain Using the Canine Brief Pain Inventory in Dogs with Osteoarthritis. Journal of Veterinary Internal Medicine, 27(1), 22–30. https://doi.org/10.1111/jvim.12004

27.  Brown, Dorothy Cimino, Bell, M., & Rhodes, L. (2013). Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis. American Journal of Veterinary Research, 74(12), 1467–1473. https://doi.org/10.2460/ajvr.74.12.1467

28.  Brown, Dorothy Cimino, Boston, R. C., Coyne, J. C., & Farrar, J. T. (2010). Development and psychometric testing of an instrument designed to measure chronic pain in dogs with osteoarthritis. American Journal of Veterinary Research, 68(6), 631–637. https://doi.org/10.2460/ajvr.68.6.631.Development

29.  Calabrò RS, Gervasi G, Marino S, Mondo PN, Bramanti P. Misdiagnosed chronic pelvic pain: pudendal neuralgia responding to a novel use of palmitoylethanolamide. Pain Med 2010; 11: 781–4.   

30.  Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature 1998; 394: 277–81.   

31.  Calignano A, La Rana G, Piomelli D. Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol 2001; 419: 191–8.   

32.  Canteri L, Petrosino S, Guida G. Riducción del consumo di antiinfiammatorios y analgésicos en el tratamiento del dolor neuropático crónico en pacientes afectados por lombosciatalgia de tipo compresivo y en tratamiento con Normast® 300 mg. Dolor 2010; 25: 227–34. 

33.  Capasso R, Izzo A, Fezza F, Pinto A, Capasso F, Mascolo N, et al. Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice. Br J Pharmacol 2001; 134: 945–50.      

34.  Carullo G, Cappello AR, Frattaruolo L, Badolato M, Armentano B, Aiello F. Quercetin and derivatives: useful tools in inflammation and pain management. Future Med Chem. 2017;9(1):79–93. doi: 10.4155/fmc-2016-0186.   [CrossRef] 

35.  Cerrato S, Brazis P, della Valle MF, Miolo A, Puigdemont A. 2010. Effects of palmitoylethanolamide on immunologically induced histamine, PGD2 and TNFα release from canine skin mast cells. Vet. Immunol. Immunopathol. 133:9–15.

36.  Cerrato, S., Brazis, P., della Valle, M. F., Miolo, A., Petrosino, S., Marzo, V. Di, & Puigdemont, A. (2012). Effects of palmitoylethanolamide on the cutaneous allergic inflammatory response in Ascaris hypersensitive Beagle dogs. Veterinary Journal, 191(3), 377–382. https://doi.org/10.1016/j.tvjl.2011.04.002

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40.  Chuang C, Martinez K, Xie G, Kennedy A, Bumrungpert A, Overman A, Jia W, Mcintosh MK. 2010. Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-a – mediated inflammation and insulin resistance in primary human adipocytes 1 – 3. Am. J. Clin. Nutr. 92:1511–1521.

41.  Cobellis L, Castaldi MA, Giordano V, Trabucco E, De Franciscis P, Torella M, et al. Effectiveness of the association micronized N‐Palmitoylethanolamine (PEA)‐transpolydatin in the treatment of chronic pelvic pain related to endometriosis after laparoscopic assessment: a pilot study. Eur J Obstet Gynecol Reprod Biol 2011; 158: 82–6.   

42.  Coburn A, Graham C, Haninger J. The effect of egg yolk in diets on anaphylactic arthritis (passive arthus phenomenon) in the guinea pig. J Exp Med 1954; 100: 425–35.       

43.  Cocito D, Peci E, Ciaramitaro P, Merola A, Lopiano L. Short‐term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain. Pain Res Treat 2014; 2014: 854560.      

44.  Colitti, M., Gaspardo, B., Della Pria, A., Scaini, C., & Stefanon, B. (2012). Transcriptome modification of white blood cells after dietary administration of curcumin and non-steroidal anti-inflammatory drug in osteoarthritic affected dogs. Veterinary Immunology and Immunopathology, 147(3–4), 136–146. https://doi.org/10.1016/j.vetimm.2012.04.001

45.  Comblain, F., Barthélémy, N., Lefèbvre, M., Schwartz, C., Lesponne, I., Serisier, S., … Henrotin, Y. (2017). A randomized, double-blind, prospective, placebo-controlled study of the efficacy of a diet supplemented with curcuminoids extract, hydrolyzed collagen and green tea extract in owner’s dogs with osteoarthritis. BMC Veterinary Research, 13(1), 1–11. https://doi.org/10.1186/s12917-017-1317-8

46.  Conaghan, P. G., Cook, A. D., Hamilton, J. A., & Tak, P. P. (2019). Therapeutic options for targeting inflammatory osteoarthritis pain. Nature Reviews Rheumatology, 15(6), 355–363. https://doi.org/10.1038/s41584-019-0221-y

47.  Conigliaro R, Drago V, Foster PS, Schievano C, Di Marzo V. Use of palmitoylethanolamide in the entrapment neuropathy of the median in the wrist. Minerva Med 2011; 102: 141–7.   

48.  Cook, A. D., Pobjoy, J., Steidl, S., Dürr, M., Braine, E. L., Turner, A. L., … Hamilton, J. A. (2012). Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development. Arthritis Research and Therapy, 14(5), R199. https://doi.org/10.1186/ar4037

49.  Cordaro M, Impellizzeri D, Paterniti I, Bruschetta G, Siracusa R, De Stefano D, Cuzzocrea S, Esposito E. 2016. Neuroprotective Effects of Co-UltraPEALut on Secondary Inflammatory Process and Autophagy Involved in Traumatic Brain Injury. J. Neurotrauma 33:132–46.

50.  Cordaro, M., Impellizzeri, D., Siracusa, R., Gugliandolo, E., Fusco, R., Inferrera, A., … Cuzzocrea, S. (2017). Effects of a co-micronized composite containing palmitoylethanolamide and polydatin in an experimental model of benign prostatic hyperplasia. Toxicology and Applied Pharmacology, 329, 231–240. https://doi.org/10.1016/j.taap.2017.06.005

51.  Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G. The endogenous fatty acid amide, palmitoylethanolamide, has anti‐allodynic and anti‐hyperalgesic effects in a murine model of neuropathic pain: involvement of CB1, TRPV1 and PPARγ receptors and neurotrophic factors. Pain 2008; 139: 541–50.   

52.  Costa B, Conti S, Giagnoni G, Colleoni M. Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo-oxygenase systems. Br J Pharmacol. 2002;137(4):413–420. doi: 10.1038/sj.bjp.0704900.      [CrossRef] 

53.  Cremon C, Stanghellini V, Barbaro MR, Cogliandro RF, Bellacosa L, Santos J, Vicario M, Pigrau M. 2017. Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome. Aliment. Pharmacol. Ther. 45:909–922.

54.  Cremon, C., Stanghellini, V., Barbaro, M. R., Cogliandro, R. F., Bellacosa, L., Santos, J., … Barbara, G. (2017). Randomised clinical trial: the analgesic properties of dietary supplementation with palmitoylethanolamide and polydatin in irritable bowel syndrome. Alimentary Pharmacology and Therapeutics, 45(7), 909–922. https://doi.org/10.1111/apt.13958

55.  Crestani F, Burato A, Michielan F. La palmitoilethanolamide micronizzata aumenta l'analgesia da agopuntura nel dolore da radicolopatia: studio pilota. G Ital Med Riabil MR 2013; 1: 49–54. 

56.  Crovace, A., Del Coco, L., Martini, F. M., Brandstetter de Bellesini, A., Miolo, A., & Fanizzi, F. P. (2017). Combining a joint health supplement with tibial plateau leveling osteotomy in dogs with cranial cruciate ligament rupture. An exploratory controlled trial. International Journal of Veterinary Science and Medicine, 5(2), 105–112. https://doi.org/10.1016/j.ijvsm.2017.09.006

57.  Crupi, R., Impellizzeri, D., Bruschetta, G., Cordaro, M., Paterniti, I., Siracusa, R., … Esposito, E. (2016). Co-ultramicronized palmitoylethanolamide/luteolin promotes neuronal regeneration after spinal cord injury. Frontiers in Pharmacology, 7(MAR), 1–12.

58.  Crupi, R., Impellizzeri, D., Bruschetta, G., Cordaro, M., Paterniti, I., Siracusa, R., … Esposito, E. (2016). Co-ultramicronized palmitoylethanolamide/luteolin promotes neuronal regeneration after spinal cord injury. Frontiers in Pharmacology, 7(MAR), 1–12.

59.  Crupi, R., Impellizzeri, D., Bruschetta, G., Cordaro, M., Paterniti, I., Siracusa, R., … Esposito, E. (2016). Co-ultramicronized palmitoylethanolamide/luteolin promotes neuronal regeneration after spinal cord injury. Frontiers in Pharmacology, 7(MAR), 1–12. https://doi.org/10.3389/fphar.2016.00047

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61.  Cuzzocrea S, Mazzon E, Esposito E, Muià C, Abdelrahman M, Di Paola R, et al. Glycogen synthase kinase-3beta inhibition attenuates the development of ischaemia/reperfusion injury of the gut. Intensive Care Med. 2007;33(5):880–893. doi: 10.1007/s00134-007-0595-1.   [CrossRef] 

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63.  D'Souza WN, Ng GY, Youngblood BD, Tsuji W, Lehto SG. A review of current animal models of osteoarthritis pain. Curr Pharm Biotechnol. 2011;12:1596–1612. doi: 10.2174/138920111798357320.  [CrossRef] 

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66.  De Filippis D, Luongo L, Cipriano M, Palazzo E, Cinelli MP, de Novellis V, et al.Palmitoylethanolamide reduces granuloma‐induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain 2011; 7: 3.      

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68.  Del Giorno R, Skaper S, Paladini A, Varrassi G, Coaccioli S. Palmitoylethanolamide in fibromyalgia: results from prospective and retrospective observational studies. Pain Ther 2015; 4: 169–78.      

69.  Desio P. Associazione tra pregabalin e palmitoiletanolamide per il trattamento del dolore neuropatico. Pathos 2010; 4: 9–14. 

70.  Di Paola R, Fusco R, Gugliandolo E, Crupi R, Evangelista M, Granese R, Cuzzocrea S. 2016. Co-micronized palmitoylethanolamide/polydatin treatment causes endometriotic lesion regression in a rodent model of surgically induced endometriosis. Front. Pharmacol. 7:1–13.

71.  Di Paola R, Impellizzeri D, Mondello P, Velardi E, Aloisi C, Cappellani A, et al.Palmitoylethanolamide reduces early renal dysfunction and injury caused by experimental ischemia and reperfusion in mice. Shock 2012; 38: 356–66.   

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