title: Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.
abstract: BACKGROUND
  Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms.
  
  
  METHODS
  PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia.
  
  
  RESULTS
  GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency.
  
  
  CONCLUSIONS
  These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed.
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. ua_pharm@yahoo.com.
authors.forename: Urooj
authors.initials: U
authors.lastname: Aman
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. fazal_subhan@upesh.edu.pk.
authors.forename: Fazal
authors.initials: F
authors.lastname: Subhan
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. shahidsalim_2002@hotmail.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahid
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. naina.akbar@yahoo.com.
authors.forename: Shehla
authors.initials: S
authors.lastname: Akbar
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. nisarahmadsatal@yahoo.com.
authors.forename: Nisar
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. gohar.pharmacist@gmail.com.
authors.forename: Gowhar
authors.initials: G
authors.lastname: Ali
authors.affiliation: Department of Pharmacy, University of Peshawar, Peshawar, 25120, Khyber Pakhtunkhwa, Pakistan. fawad.khwaja@yahoo.com.
authors.forename: Khwaja
authors.initials: K
authors.lastname: Fawad
authors.affiliation: Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, CF10 3NU, UK. sewell@cardiff.ac.uk.
authors.forename: Robert D E
authors.initials: RD
authors.lastname: Sewell
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy; D000700:Analgesics / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D000701:Analgesics, Opioid; D000818:Animals; D014151:Anti-Anxiety Agents / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D018755:GABA Agonists / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy*; D006993:Hypnotics and Sedatives / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008807:Mice, Inbred BALB C; D009437:Neuralgia / Q000188:drug therapy; D029598:Passiflora / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D056650:Vulvodynia / Q000188:drug therapy*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D014151:Anti-Anxiety Agents; D005227:Fatty Acids; D018755:GABA Agonists; D006993:Hypnotics and Sedatives; D010936:Plant Extracts