Post-ictal analgesia in genetically epilepsy-prone rats is induced by audiogenic seizures and involves cannabinoid receptors in the periaqueductal gray

Brain Res. 2011 May 10;1389:177-82. doi: 10.1016/j.brainres.2011.03.041. Epub 2011 Mar 22.


Post-ictal depression of consciousness occurs after generalized convulsive seizures, and includes analgesia, lasting for hours after electrically or chemically induced seizures in animals. The brain sites and mechanisms, mediating post-ictal analgesia, are unclear. The ventrolateral periaqueductal gray (PAG) is an important neuronal network site for mediating analgesia and also in generalized seizures, particularly in genetically epilepsy-prone rats (GEPRs). Endocannabinoids are implicated in mediating analgesia in several brain sites, including the PAG, and generalized seizures result in endocannabinoid release. This study evaluated if post-ictal analgesia occurs in GEPRs, following audiogenic seizures (AGS), and whether this analgesia involves endocannabinoid actions in PAG. Analgesia was evaluated, using thermal stimulation to evoke nociception, measuring changes in paw withdrawal latencies (PWLs) induced by AGS. Endocannabinoid involvement in post-ictal analgesia in GEPRs was evaluated, using focal bilateral microinjection of a cannabinoid (CB1) receptor antagonist (AM251) into PAG. AGS induced a significant increase in PWLs, lasting for ≥120min. Microinjection of AM251 (100 and 200, but not 50 pmol/side) into PAG significantly decreased post-ictal analgesia in GEPRs. Endocannabinoids are also known to activate transient receptor potential vanilloid (TRPV1) receptors, but PAG microinjection of a TRPV1 receptor antagonist (capsazepine) did not affect post-ictal analgesia in GEPRs. These results indicate that AGS in GEPRs induce post-ictal analgesia, which is the first observation of this phenomenon in a genetic epilepsy model. These findings suggest an important role of PAG in post-ictal analgesia. The results also suggest that CB1 receptors in PAG are critical for mediating post-ictal analgesia in GEPRs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnesia, Anterograde / metabolism*
  • Analgesia
  • Animals
  • Epilepsy, Reflex / complications*
  • Epilepsy, Reflex / metabolism
  • Female
  • Male
  • Pain Threshold / physiology
  • Periaqueductal Gray / metabolism*
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Seizures / complications*
  • Seizures / metabolism


  • Cnr1 protein, rat
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251