P-glycoprotein inhibitors improve effective dose and time of pregabalin to inhibit intermittent cold stress-induced central pain

J Pharmacol Sci. 2016 May;131(1):64-7. doi: 10.1016/j.jphs.2016.01.002. Epub 2016 Jan 14.


Pregabalin (PGB) is a valuable therapeutic drug against chronic pain. Here we attempted to perform the combinatorial drug therapy with P-glycoprotein (P-gp) inhibitors to lower therapeutic dosage of PGB in the intermittent cold stress-induced fibromyalgia-like pain model. Single intracerebroventricular (i.c.v.) PGB injection exerted long-lasting anti-hyperalgesic effects for 72 h, while the effect of PGB given intraperitoneally (i.p.) disappeared within 3 h. Importantly, the pretreatment with P-gp inhibitors markedly prolonged the PGB (i.p.) effects, which lasted for 72 h. These results suggest that the combinatorial treatment with P-gp inhibitor enables the prolongation of dose-interval for PGB.

Keywords: Fibromyalgia; P-glycoprotein; Pregabalin.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Analgesics / therapeutic use*
  • Animals
  • Chronic Pain / drug therapy
  • Cold Temperature
  • Cyclosporins / therapeutic use*
  • Drug Therapy, Combination
  • Fibromyalgia / drug therapy*
  • Hyperalgesia / drug therapy
  • Male
  • Mice, Inbred C57BL
  • Neuralgia / drug therapy
  • Pregabalin / therapeutic use*
  • Sciatic Nerve / surgery


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Analgesics
  • Cyclosporins
  • Pregabalin
  • valspodar