EFFECT OF ACUTE PSILOCYBIN ON THERMAL AND NEUROPATHIC PAIN IN RODENTS
Notice bibliographique
Résumé
Abstract Background Pain is a major health problem resulting in a high degree of suffering, physical, psychological and social impairments, and exorbitant health care costs1-2. Effective pain treatments are limited and are often accompanied by significant side effects3. Preclinical and clinical studies suggest that psychedelics, specifically psilocybin, can reset brain areas of functional connectivity that have a profound impact on central neuropathic states4. 5HT2A receptors have been implicated in both nociceptive pathways and the mechanism of action of psychedelics4. However, the effect of psychedelics on pain mechanisms is not fully understood. Aim and Objectives In this study, we examined the effect of psilocybin two models of pain: hot plate to investigate acute pain responses and the sciatic nerve ligation to assess the neuropathic pain antiallodynic responses. Method The hot plate test (HPT, Ugo Basile, Italy) was used to determine the acute thermal nociception. Mice (C57BL/6) were randomized and either veh (saline i.p.) or psilocybin (3 mg/kg i.p.) was administered. Mice were introduced to the hot plate at an initial temperature of 37° C with a near linear increase of 3° C per min. The nociceptive endpoint was established as the temperature eliciting a fast hind paw lick and/or paw withdrawal. To investigate chronic pain, we induced neuropathic pain (Sciatic Nerve Ligation) in Wistar rats. Neuropathy was determined using the von Frey (VF) filaments 14 days post-surgery. Animals who developed neuropathy were treated acutely with psilocybin (3 and 10 mg/kg, i.p.) or vehicle (saline, i.p.) and mechanical allodynia was assessed at time 0 (before administration), 0.5, 1, 2, 3, and 4 hours after administration. Results Acute systemic administration of psilocybin (3 mg/kg, i.p) did not increase thermal withdrawal threshold compared to vehicle-treated mice (t=0.4557, p= 0.6607, vehicle mean: 15.6 ± 2.657, n=5; psilocybin mean: 17.28 ± 2.556, n=5). On the other hand, in the NP model, psilocybin at the doses of 3 mg/kg and 10 mg/kg significantly increased mechanical withdrawal threshold compared to vehicle at time 0.5 hours (3mg/kg, p=0.0066, 10mg/kg, p=0.0012), 1 hour (3mg/kg, p=0.0043, 10mg/kg, p=0.0110), and 2 hours (3mg/kg, p=0.0051, 10mg/kg, p=0.0410), with no significant differences between doses of 3 and 10 mg (two-way ANOVA repeated measures, followed by Bonferroni’ s post-hoc test) Discussion and Conclusion These preliminary findings suggest that acute systemic administration of psilocybin has antiallodynic effect on NP, concurring with previous findings5-6, but demonstrates no nociceptive effect on acute thermal pain. Furthermore, this suggests that the action of psilocybin on pain reduction may specifically target NP, rather than generalized nociception of acute pain. Therefore, psilocybin may have a potential in the treatment neuropathic pain. References 1.-Raffaeli, W., &Arnaudo, E. (2017). Pain as a disease: An overview. Journal of Pain Research, 10, 2003–2008. https://doi.org/10.2147/JPR.S138864 2.- Loeser, J. D., &Melzack, R. (1999). Pain: An overview. The Lancet, 353(9164), 1607–1609. https://doi.org/10.1016/S0140-6736(99)01311-2 3.-Curatolo, M., &Bogduk, N. (2001). Pharmacologic Pain Treatment of Musculoskeletal Disorders: Current Perspectives and Future Prospects. The Clinical Journal of Pain, 17(1), 25. 4.-Castellanos, J. P., Woolley, C., Bruno, K. A., Zeidan, F., Halberstadt, A., &Furnish, T. (2020). Chronic pain and psychedelics: A review and proposed mechanism of action. Regional Anesthesia &Pain Medicine, 45(7), 486–494. https://doi.org/10.1136/rapm-2020-101273 5.- Kolbman, N., Liu, T., Guzzo, P., Gilligan, J. P., Mashour, G. A., Vanini, G., &Pal, D. (2023). Intravenous psilocybin administration attenuates mechanical hypersensitivity in a rat model of chronic pain [Preprint]. Neuroscience. https://doi.org/10.1101/2023.08.26.554802 6.-Lyes, M., Yang, K. H., Castellanos, J., &Furnish, T. (2023). Microdosing psilocybin for chronic pain: A case series. Pain, 164(4), 698–702. https://doi.org/10.1097/j.pain.0000000000002778
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».