Dataset Information

Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury.

ABSTRACT: Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. This study tested the hypothesis that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain.Anesthetized rats received 0.75-cm third-degree burn on dorsal hind paw. Vehicle or AM251 30 ?g intrathecally (older rats, n=6 per group) or, either vehicle, 0.1 or 1.0 mg/kg intraperitoneally (younger rats, n=6 per group), started immediate postburn, was administered for 7 days. Mechanical allodynia and thermal hyperalgesia were tested on ventral paw for 14 days. Microglial and astroglial activity was assessed by immunocytochemistry.Allodynia, observed on burn side from day 1 to 14, was significantly (P<0.05) attenuated by intrathecal and intraperitoneal AM251 (1 mg/kg) starting from 3 to 14 days. Hyperalgesia, observed from day 3 to 12, was completely (P<0.05) reversed by intrathecal and intraperitoneal AM251 (1 mg/kg). AM251 0.1 mg/kg had no effect. Microglial activity (n=3 per time point) increased (P<0.05) 18.5±7.5 and 12.3±1.6 (mean±SD) fold at 7 and 14 days, respectively. Astroglial activity (n=4 per time point) increased 2.9±0.3 fold at day 7 only. Glial activities were unaltered by AM251.AM251 inhibited nociceptive behaviors after burn even beyond 7-day period of administration. Although many studies have documented the utility of CB1R agonists, this study indicates that endogenous cannabinoids may have an unexpected pronociceptive effect during development of burn pain, explaining why CB1R antagonist, AM251, improves nociceptive behaviors. The decreased nociception with AM251 without altering glial activity indicates that AM251 acts further downstream of activated glial cells.

SUBMITTER: Ueda M

PROVIDER: S-EPMC4237656 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury.

Ueda Masashi M Iwasaki Hajime H Wang Shuxing S Murata Eri E Poon K Y Trudy KY Mao Jianren J Martyn J A Jeevendra JA

Anesthesiology 20141201 6

<h4>Background</h4>Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. This study tested the hypothesis that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain.<h4>Methods</h4>Anesthetized rats received 0.75-cm third-degree burn on dorsal hind paw. Vehicle or AM251 30 μg intrathecally (older rats, n=6 per group) or, either vehicle, 0.1 or 1.0 mg/kg intraperitoneally (you ...[more]

PMID: 25188001

Similar Datasets

Project description:IntroductionThe aim of this study was to observe the effect of stress caused by neuropathic pain on serum cortisol concentration and expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal cord and dorsal root ganglions (DRG) and investigate the role and mechanism of curcumin in the neuropathic pain of stressful rats. Neuropathic pain is a prevalent disease that greatly impairs the patients' quality of life. A lack of the understanding of its etiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on expression of 11β-hydroxysteroid dehydrogenase type I enzyme (11βHSD1) in spinal dorsal horn and DRG in chronic constriction injury (CCI) mode of neuropathic pain of rats.MethodsSeventy-two male Sprague-Dawley rats were randomized into four groups with 18 rats in each: sham operation group (Sham), chronic constrictive injury group (CCI), solvent contrast group (SC), and curcumin-treated group (Cur100). Curcumin, 100 mg/kg/day intraperitoneal, was given for 14 days starting from the first day after operation in the Cur100 group. Paw thermal withdrawal latency (PTWL) and paw mechanical withdrawal threshold (PMWT) of rats were measured 2 days pre-operative, and 1, 3, 5, 7, 10, and 14 days post-operative. The animals were deeply anesthetized and blood was taken from the heart, the lumbar segment (L4, 5) of the spinal cord and DRG were dissected out and homogenized. The change of cortisol was measured by enzyme-linked immunosorbent assay and the change of 11βHSD1 expression was determined by immunochemistry and Western blot.ResultsCompared with sham group, PTWL and PMWT significantly decrease after operation in the CCI group; serum cortisol concentration was significantly increased and the expression of 11βHSD1 was significantly increased in the CCI group. Comparing with CCI group, the PMWT and PTWL were increased and the serum cortisol concentration was decreased and the expression of 11βHSD1 was inhibited in Cur100 group.ConclusionStress caused by neuropathic pain triggers release of cortisol to the blood and expression of 11βHSD1 would increase at the same time. Curcumin could alleviate thermal and mechanical hyperalgesia induced by CCI and inhibit the serum cortisol concentration and expression of 11βHSD1 in the spinal cord and DRG.

Dataset Information

Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury.

Publications

Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets