N-palmitoylethanolamide in the anterior cingulate cortex attenuates inflammatory pain behaviour indirectly via a CB1 receptor-mediated mechanism
| Autor: | Brendan Harhen, Bright N. Okine, Manish K. Madasu, David P. Finn, Charles Prendergast, Jessica C. Gaspar, Michelle Roche, Fiona McGowan |
|---|---|
| Přispěvatelé: | Science Foundation Ireland, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil, College of Science, National University of Ireland, Galway |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male PREFRONTAL CORTEX Cohort Studies Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Receptor Cannabinoid CB1 Pain Measurement ESCAPE/AVOIDANCE BEHAVIOR Chemistry Central nucleus of the amygdala Anti-Inflammatory Agents Non-Steroidal NEUROPATHIC PAIN food and beverages Endocannabinoid system medicine.anatomical_structure Neurology Ethanolamines lipids (amino acids peptides and proteins) Diterpenes Microdissection Proto-Oncogene Proteins c-fos Locomotion psychological phenomena and processes medicine.drug AM251 medicine.medical_specialty NOXIOUS STIMULI Microinjections TRPV1 Pain Palmitic Acids RAT-BRAIN Gyrus Cinguli 03 medical and health sciences Fixatives Internal medicine Formaldehyde medicine Animals FATTY-ACID AMIDE Cannabinoid Receptor Antagonists CANNABINOID RECEPTOR Palmitoylethanolamide Amides Rats PPAR gamma AMYGDALA MODEL Disease Models Animal 030104 developmental biology Anesthesiology and Pain Medicine Endocrinology ANANDAMIDE nervous system Cannabinoid receptor antagonist Neurology (clinical) Rostral ventromedial medulla Neuroscience 030217 neurology & neurosurgery Basolateral amygdala |
| Popis: | The neural substrates and mechanisms mediating the antinociceptive effects of the endogenous bioactive lipid, N-palmitoylethanolamide (PEA), require further investigation. We investigated the effects of exogenous PEA administration into the anterior cingulate cortex (ACC), an important brain region linked with cognitive and affective modulation of pain, on formalin-evoked nociceptive behaviour in rats. Potential involvement of peroxisome proliferator-activated receptor isoforms (PPAR) a and g or endocannabinoid-mediated entourage effects at cannabinoid(1) (CB1) receptors or transient receptor potential subfamily V member 1 (TRPV1) in mediating the effects of PEA was also investigated. Intra-ACC administration of PEA significantly attenuated the first and early second phases of formalin-evoked nociceptive behaviour. This effect was attenuated by the CB1 receptor antagonist AM251, but not by the PPAR alpha antagonist GW6471, the PPAR gamma antagonist GW9662, or the TRPV1 antagonist 5'-iodo resiniferatoxin. All antagonists, administered alone, significantly reduced formalin-evoked nociceptive behaviour, suggesting facilitatory/permissive roles for these receptors in the ACC in inflammatory pain. Post-mortem tissue analysis revealed a strong trend for increased levels of the endocannabinoid anandamide in the ACC of rats that received intra-ACC PEA. Expression of c-Fos, a marker of neuronal activity, was significantly reduced in the basolateral nucleus of the amygdala, but not in the central nucleus of the amygdala, the rostral ventromedial medulla or the dorsal horn of the spinal cord. In conclusion, these data indicate that PEA in the ACC can reduce inflammatory pain-related behaviour, possibly via AEA-induced activation of CB1 receptors and associated modulation of neuronal activity in the basolateral amygdala. This work was funded by a Principal Investigator Programme Grant from Science Foundation Ireland (10/IN.1/B2976), a PhD fellowship to JCG from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil (207530/2014-9), and a PhD Fellowship to MKM from the College of Science, NUI Galway. peer-reviewed |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|