Palmitoylethanolamide Relieves Pain and Preserves Pancreatic Islet Cells in a Murine Model of Diabetes
Abstract
We previously demonstrated that the intraperitoneal administration of palmitoylethanolamide (PEA) in mice with chronic constriction injury of the sciatic nerve evoked a relief of both thermal hyperalgesia and mechanical allodynia in neuropathic mice. Since diabetic neuropathy is one of the most common long-term complications of diabetes, we explored the ability of PEA to also relief this kind of chronic pain, employing the well established streptozotocin-induced animal model of type 1 diabetes. Our findings demonstrated that PEA relieves mechanical allodynia, counteracts nerve growth factor deficit, improves insulin level, preserves Langerhans islet morphology reducing the development of insulitis in diabetic mice. These results suggest that PEA could be effective in type 1-diabetic patients not only as pain reliever but also in controlling the development of pathology.
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Acute and repeated PEA administration evoked anti-allodynic effects in diabetic mice without the development of tolerance that required the activation of CB1, CB2, TRPV1, PPAR-α and PPAR-γ receptors.
“Additionally, acute and repeated PEA administration evoked anti-allodynic effects in diabetic mice without the development of tolerance that required the activation of CB 1, CB 2, TRPV1, PPAR-α and PPAR-γ receptors (Donvito et al, 2015) (Table 5).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Donvito et al, 2015
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Petrosino, S., & Marzo, V. D. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13580 · Cited by 333 · see citing works
“…model of streptozotocininduced type 1 diabetes, it has been recently observed that PEA treatment (i.p.) was not only able to relieve mechanical allodynia but also to improve insulin levels and preserve Langerhans islet morphology by reducing the development of insulitis (Donvito et al., 2015).”
BackgroundDonvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301 · see citing works
Self-citationPetrosino, S., Cordaro, M., Verde, R., Moriello, A. S., Marcolongo, G., Schievano, C., Siracusa, R., Piscitelli, F., Peritore, A. F., Crupi, R., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00249 · Cited by 89 · see citing works
“…reducing their number (De Filippis et al., 2011; Iuvone et al., 2016) and activation state (i.e., mediator release; Facci et al., 1995; Mazzari et al., 1996; Cerrato et al., 2010; Cantarella et al., 2011; Esposito et al., 2011; De Filippis et al., 2013; Donvito et al., 2015; Abramo et al., 2017).”
BackgroundChronic Pain in the Elderly: The Case for New Therapeutic Strategies
Varrassi, G. (2015) · Pain Physician · doi:10.36076/ppj.2015/18/e863 · Cited by 77 · see citing works
Okine, B. N., Gaspar, J. C., & Finn, D. P. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14339 · Cited by 71 · see citing works
“While the former account primarily for the anti-inflammatory effects associated with PPAR activation, the non-genomic mechanisms are thought to underlie the rapid antinociceptive effects of not only PEA but also other synthetic PPAR agonists in animal models of inflammatory and neuropathic pain (Churi et al., 2008, Lo…”
BackgroundPalmitoylethanolamide Reverses Paclitaxel-Induced Allodynia in Mice
Donvito, G., Wilkerson, J. L., Damaj, M. I., & Lichtman, A. H. (2016) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.116.236182 · Cited by 50 · see citing works
“310 and mechanical allodynia in the mouse sciatic nerve injury model of neuropathic pain (Costa et al., 2008), as well as reverse allodynia in mouse model of diabetes-induced peripheral neuropathy (Donvito et al., 2015).”
BackgroundResultInfluentialSelf-citationChronic prostatitis: current treatment options
Pirola, G. M., Verdacchi, T., Rosadi, S., Annino, F., & Angelis, M. D. (2019) · Research and Reports in Urology · doi:10.2147/rru.s194679 · Cited by 40 · see citing works
“44 Histological fi ndings in CP/CPPS patients' prostates often show in fi ltrating lymphocytes and macrophages around glandular elements, and therefore PEA could have similar neuronal and immune-modulating effects on prostatic cells.”
Rocca, G. D., & Gamba, D. (2021) · Animals · doi:10.3390/ani11040952 · Cited by 29 · see citing works
Tobias, J. M., Rajic, G., Viray, A. E. G., Icka-Araki, D., & Frank, J. A. (2021) · Chemical Science · doi:10.1039/d1sc02527a · Cited by 22 · see citing works
The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review
Davis, M. P., Behm, B., Mehta, Z. Y., & Fernandez, C. (2019) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/1049909119850807 · Cited by 19 · see citing works
Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
Elfarnawany, A., & Dehghani, F. (2022) · Biomolecules · doi:10.3390/biom12121873 · Cited by 15 · see citing works
“PEA is a bioactive lipid that is used as an anti-nociceptive agent in different animal models of neuropathic pain, including spinal cord injury [56] and diabetes-induced peripheral neuropathy [57].”
BackgroundGaspar, J. C., Healy, C. R., Ferdousi, M. I., Roche, M., & Finn, D. P. (2021) · Biomedicines · doi:10.3390/biomedicines9060610 · Cited by 14 · see citing works
A Brief Review on the Novel Therapies for Painful Diabetic Neuropathy
Basem, J. I., Bah, F. N., & Mehta, N. D. (2023) · Current Pain and Headache Reports · doi:10.1007/s11916-023-01126-1 · Cited by 12 · see citing works
Déciga‐Campos, M., & Ortíz‐Andrade, R. (2015) · Drug Development Research · doi:10.1002/ddr.21259 · Cited by 10 · see citing works
“Additionally, the present results are consistent with the hyperalgesia and mechanical allodynia induced by chronic constriction injury of the sciatic nerve in a mouse model of persistent pain [Costa et al., 2008; Donvito et al., 2015].”
BackgroundResultPalmitoylethanolamide causes dose-dependent changes in brain function and the lipidome
Balaji, S., Woodward, T. J., Richter, E., Chang, A., Otiz, R., Kulkarni, P. P., Balaji, K., Bradshaw, H. B., & Ferris, C. F. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1506352 · Cited by 10 · see citing works
The Endocannabinoid System as a Therapeutic Target in Diabetic Peripheral Neuropathic Pain
Bagher, A. M. (2021) · Journal of Microscopy and Ultrastructure · doi:10.4103/jmau.jmau_97_20 · Cited by 9 · see citing works
“neutralized the nerve growth factor deficit, and improved insulin levels in STZ-induced diabetic mice.[75] Importantly,”
BackgroundInfluentialPalazzo, E., Luongo, L., Guida, F., de Novellis, V., Boccella, S., Cristiano, C., Marabese, I., & Maione, S. (2019) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000549 · Cited by 8 · see citing works
“Other proposed mechanisms for PEA in counteracting pain include ATP-sensitive K+ channels [88], transient receptor potential (TRP) channels [117], NF-kB [90], Ca2+-activated potassium channels [105] and NR2b subunit of NMDA receptor [103].”
BackgroundClassical and Unexpected Effects of Ultra-Micronized PEA in Neuromuscular Function
Cifelli, P., Ruffolo, G., Ceccanti, M., Cambieri, C., Libonati, L., Palma, E., & Inghilleri, M. (2022) · Biomolecules · doi:10.3390/biom12060758 · Cited by 6 · see citing works
“PEA treatment was also able to preserve Langerhans islets’ morphology in the pancreatic gland of diabetic mice [89].”
Background
- Authors
- Donvito, G., Bettoni, I., Comelli, F., Colombo, A., & Costa, B.
- Affiliations
- University of Milano-Bicocca (IT)
- Venue
- CNS & Neurological Disorders - Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-05-07
- Volume
- 14
- Issue
- 4
- Pages
- 452-462
- ISSN
- 1568-007X (ISSN-L)
- 1871-5273
- OpenAlex
- W2239327731
- Cited by
- 19
- References
- 0
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS & Neurological Disorders - Drug Targets (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- palmitoylethanolamide, diabetic neuropathy, type 1 diabetes, mechanical allodynia, neuropathic pain, nerve growth factor, insulin, insulitis, streptozotocin-induced diabetes, analgesic effect
- MeSH terms
- Amides, Analgesics, Animals, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Ethanolamines, Hyperalgesia, Islets of Langerhans, Male, Pain, Pain Measurement, Palmitic Acids, Sciatic Nerve, Nerve Growth Factor, Mice
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