title: Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure.
abstract: OBJECTIVE
  Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice.
  
  
  METHODS
  To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion.
  
  
  RESULTS
  In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration.
  
  
  CONCLUSIONS
  PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations.
authors.affiliation: Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Moshiri
authors.affiliation: Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Adel
authors.initials: SA
authors.lastname: Moallem
authors.affiliation: Milad Infertility Center, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Armin
authors.initials: A
authors.lastname: Attaranzadeh
authors.affiliation: Nanotechnology Research Center School of Pharmacy, Mashhad University Medical Sciences, Mashhad, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Saberi
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Etemad
keywords: Acute; Muscle injury; Pregabalin; Skeletal muscle; Subacute