Loading

logo

Journal of Pain Research and Management

ISSN: 3067-9427

Original Research Open Access

Antinociceptive effect of N,N-dimethyltryptamine (DMT) involving serotonergic, opioidergic, cannabinoidergic, and nitrergic systems in PGE2-induced hyperalgesia in rats

Flávia C.S. Fonseca 1, Daniel P.D. Machado 1, André D. Cavalcante1, Andrea C. Perez 1, Thiago R.L. Romero 1, Igor D.G. Duarte 1,*
  • 1Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil
+ Affiliations - Affiliations

Corresponding Author

Igor D.G. Duarte, dimitri@icb.ufmg.br

Received Date: September 12, 2025

Accepted Date: January 05, 2026

Citation:

Fonseca FCS, Machado DPD, Cavalcante AD, Perez AC, Romero TRL, Duarte IDG. Antinociceptive effect of N,N-dimethyltryptamine (DMT) involving serotonergic, opioidergic, cannabinoidergic, and nitrergic systems in PGE2-induced hyperalgesia in rats. J Pain Res Manag. 2026;2(1):10-18.


Copyright: © © 2026 Fonseca FCS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

N,N-dimethyltryptamine (DMT) is an alkaloid structurally similar to serotonin that acts on serotonergic receptors. This study aimed to evaluate the effects of DMT on peripheral nociception and explore its possible mechanisms of action. Male Wistar rats underwent a mechanical paw pressure test, with hyperalgesia induced by intraplantar injection of prostaglandin E2 (PGE2; 2 µg/paw). Pretreatment with ketanserin, ondansetron, isamoltan, naloxone, AM251, AM630, L-NOArg, or glibenclamide was administered 35 minutes before testing. Nociceptive thresholds were measured 180 minutes after PGE2 injection. DMT (2.5, 10, and 40 μg/paw) showed a dose-dependent peripheral antinociceptive effect against PGE2-induced hyperalgesia, with the highest dose not affecting the contralateral paw. The antinociceptive effect of DMT was partially blocked by selective 5-HT2A (ketanserin; 10 μg/paw) and 5-HT3 (ondansetron; 10 μg/paw) receptor antagonists but not by a selective 5-HT1B receptor antagonist (isamoltan; 10 μg/paw). A non-selective opioid receptor antagonist (naloxone; 50 μg/paw) completely reversed DMT-induced peripheral antinociception, while selective CB1 (AM251; 80 μg/paw) and CB2 (AM630; 100 μg/paw) cannabinoid receptor antagonists partially blocked this effect. Additionally, a non-selective nitric oxide synthase inhibitor (L-NOArg; 24 μg/paw) partially reversed DMT’s antinociceptive effect, which remained unaffected by the selective ATP-sensitive calcium channel blocker (glibenclamide; 80 μg/paw). These findings suggest that DMT exhibits peripheral antinociceptive activity, involving opioid receptors, CB1 and CB2 cannabinoid receptors, 5-HT2A and 5-HT3 serotonergic receptors, and NOS enzymes. 

Keywords

Serotonin, Cannabinoid, Opioid, Nitric oxide, Pain

Recommended Articles

Neodymium:YAG laser posterior capsulotomy in the lateral decubitus position

Here we report a novel method of performing a Neodyminium:YAG (Nd:YAG) laser posterior capsulotomy in an adult patient, unable to tolerate the procedure awake with topical anaesthesia in the outpatient clinic setting. The procedure was performed by altering the chin rest and arms of the Nd:YAG laser machine so that the procedure could be undertaken in an anaesthetized patient in the operating theatre, in the lateral decubitus position, with the laser machine upright in its normal position.

Presbyopia correcting IOLs and the ocular surface disease… The good, the bad and the ugly

The last two decades were especially fruitful for the refractive surgeons and for the industry who have been showing tremendous development in both understanding and meeting patients’ desire for spectacle independence. Ever since the first trials from Dr. Kenneth Hoffer with his early 1980’s effort in producing a multifocal IOL to the latest achievements from different companies in putting trifocals and EDOF optics to the market.

How many mutations does it take to make a uveal melanoma?

Uveal melanoma (UM) is a rare cancer that affects the choroid and, less frequently, the ciliary body or the iris (for recent reviews see [1-3]). Despite a profound knowledge of the oncogenic mechanisms behind UM tumorigenesis and despite an accurate cytogenetic and molecular prognosis, only limited advances have been made in UM therapy.

MSICS is a Simple Solution for a Big Problem

Manual small-incision cataract surgery (MSICS) is a sutureless cataract surgery that has multiple advantages over traditional phacoemulsification and extracapsular cataract extraction (ECCE) procedures. SICS became the procedure of choice for international ophthalmology, where the microscopes and operating room can be more challenging, in addition to the more advanced pathology often seen.

Surgical smoke and SARS-CoV-2 transmission

The protection of health care workers from nosocomial infection is a paramount consideration in the current pandemic involving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Not only is prevention of viral transmission the most effective means to lessen the public health impact of coronavirus disease 2019 (COVID-19), but also both quarantine and illness – that disproportionately affect health care workers – have devastating effects on the ability of hospitals to adequately care for increased patient loads.

Full Text
Cite
Download PDF
Author Information X