Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache

Caroline M. Kopruszinski, Edita Navratilova, Barbora Vagnerova, Juliana Swiokla, Amol Patwardhan, David William Dodick, Frank Porreca

Research output: Contribution to journalArticle

Abstract

Aim: Evaluation of cannabinoid receptor agonists in a preclinical model of medication overuse headache. Methods: Female Sprague Dawley rats received graded intraperitoneal doses of WIN55,212-2 or Δ-9-tetrahydrocannabinol (Δ-9-THC). Antinociception (tail-flick test), catalepsy and hypomotility (open field test) and impairment of motor function (rotarod test) were assessed to establish effective dosing. Rats were then treated twice daily with equianalgesic doses of WIN55,212-2 or Δ-9-THC, or vehicle, for 7 days and cutaneous tactile sensory thresholds were evaluated during and three weeks following drug discontinuation. Rats then received a one-hour period of bright light stress (BLS) on two consecutive days and tactile sensory thresholds were re-assessed. Results: WIN55,212-2 and Δ-9-THC produced antinociception as well as hypomotility, catalepsy and motor impairment. Repeated administration of WIN55,212-2 and Δ-9-THC induced generalized periorbital and hindpaw allodynia that resolved within 3 weeks after discontinuation of drug. Two episodes of BLS produced delayed and long-lasting periorbital and hindpaw allodynia selectively in rats previously treated with WIN55,212-2, and Δ-9-THC. Interpretation: Cannabinoid receptor agonists including Δ-9-THC produce a state of latent sensitization characterized by increased sensitivity to stress, a presumed migraine trigger. Overuse of cannabinoids including cannabis may increase the risk of medication overuse headache in vulnerable individuals.

Original languageEnglish (US)
JournalCephalalgia
DOIs
StateAccepted/In press - Jan 1 2019

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Secondary Headache Disorders
Dronabinol
Cannabinoids
Sensory Thresholds
Cannabinoid Receptor Agonists
Catalepsy
Hyperalgesia
Touch
Rotarod Performance Test
Light
Cannabis
Migraine Disorders
Pharmaceutical Preparations
Sprague Dawley Rats
Tail
Skin

Keywords

  • cannabis
  • medication overuse headache
  • Migraine
  • sensitization
  • stress
  • Δ-9-THC

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Kopruszinski, C. M., Navratilova, E., Vagnerova, B., Swiokla, J., Patwardhan, A., Dodick, D. W., & Porreca, F. (Accepted/In press). Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache. Cephalalgia. https://doi.org/10.1177/0333102419865252

Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache. / Kopruszinski, Caroline M.; Navratilova, Edita; Vagnerova, Barbora; Swiokla, Juliana; Patwardhan, Amol; Dodick, David William; Porreca, Frank.

In: Cephalalgia, 01.01.2019.

Research output: Contribution to journalArticle

Kopruszinski, Caroline M. ; Navratilova, Edita ; Vagnerova, Barbora ; Swiokla, Juliana ; Patwardhan, Amol ; Dodick, David William ; Porreca, Frank. / Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache. In: Cephalalgia. 2019.
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