Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception

Aldric Hama, Jacqueline Sagen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The endogenous nonapeptide hemopressin (HE) demonstrates potent block of the cannabinoid subtype-1 (CB1) receptor in vitro and robust antinociception in vivo. The current study evaluated the effects of centrally administered HE in mechanistically distinct pre-clinical rat models of pain-the hot plate test and the hind paw formalin test. The non-subtype selective CB receptor agonist WIN 55,212-2 was tested concurrently as a positive control. In the hot plate test, neither intrathecal (i.t.) HE nor WIN 55,212-2 significantly altered the latency to respond to noxious heat. By contrast, i.t. HE and WIN 55,212-2 significantly reduced pain-related behaviors in the formalin test. Possible HE functionality as a CB1 receptor antagonist at the spinal level was evaluated in the formalin test. Intrathecal pretreatment with HE did not attenuate the antinociceptive effect of i.t. WIN 55,212-2. However, pretreatment with the CB1 receptor antagonist rimonabant did; i.t. rimonabant pretreatment was not antinociceptive. Potential supraspinal antinociceptive activity of HE was also evaluated. Whereas intracerebroventricular (i.c.v.) injection of WIN 55,212-2 reduced pain-related behaviors in the formalin test, interestingly, i.c.v. HE increased behaviors. In the current study, an antinociceptive effect with the CB receptor ligand HE was obtained under the specific condition of tissue injury and not in the uninjured state. Thus, HE could be a useful analgesic peptide with a novel spinal mechanism of action.

Original languageEnglish
Pages (from-to)340-346
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume100
Issue number2
DOIs
StatePublished - Dec 1 2011

Fingerprint

Cannabinoid Receptors
Nociception
Rats
Ligands
rimonabant
Pain Measurement
Formaldehyde
Cannabinoids
Pain
hemopressin
Analgesics
Hot Temperature
Win 55212-2
Tissue

Keywords

  • Acute nociception
  • Formalin tests
  • Hemopressin
  • Intracerebroventricular
  • Intrathecal
  • SR 141716
  • WIN 55,212-2

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this

Centrally mediated antinociceptive effects of cannabinoid receptor ligands in rat models of nociception. / Hama, Aldric; Sagen, Jacqueline.

In: Pharmacology Biochemistry and Behavior, Vol. 100, No. 2, 01.12.2011, p. 340-346.

Research output: Contribution to journalArticle

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