The analgesic and anticonvulsant effects of piperine in mice

J Physiol Pharmacol. 2013 Dec;64(6):789-94.


Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid
  • Alkaloids / therapeutic use*
  • Analgesics / therapeutic use*
  • Animals
  • Anticonvulsants / therapeutic use*
  • Benzodioxoles / therapeutic use*
  • Hot Temperature
  • Male
  • Mice
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain / drug therapy*
  • Pain / etiology
  • Pentylenetetrazole
  • Picrotoxin
  • Piper nigrum*
  • Piperidines / therapeutic use*
  • Polyunsaturated Alkamides / therapeutic use*
  • Seizures / chemically induced
  • Seizures / drug therapy*


  • Alkaloids
  • Analgesics
  • Anticonvulsants
  • Benzodioxoles
  • Narcotic Antagonists
  • Piperidines
  • Polyunsaturated Alkamides
  • Picrotoxin
  • Naloxone
  • Acetic Acid
  • piperine
  • Pentylenetetrazole