title: Analgesic properties of loperamide differ following systemic and local administration to rats after spinal nerve injury.
abstract: BACKGROUND
  The analgesic properties and mechanisms of loperamide hydrochloride, a peripherally acting opioid receptor agonist, in neuropathic pain warrant further investigation.
  
  
  METHODS
  We examined the effects of systemic or local administration of loperamide on heat and mechanical hyperalgesia in rats after an L5 spinal nerve ligation (SNL).
  
  
  RESULTS
  (1) Systemic loperamide (0.3-10 mg/kg, subcutaneous in the back) dose dependently reversed heat hyperalgesia in SNL rats, but did not produce thermal analgesia. Systemic loperamide (3 mg/kg) did not induce thermal antinociception in naïve rats; (2) systemic loperamide-induced anti-heat hyperalgesia was blocked by pretreatment with intraperitoneal naloxone methiodide (5 mg/kg), but not by intraperitoneal naltrindole (5 mg/kg) or intrathecal naltrexone (20 μg/10 μL); (3) local administration of loperamide (150 μg), but not vehicle, into plantar or dorsal hind paw tissue induced thermal analgesia in SNL rats and thermal antinociception in naïve rats; (4) the analgesic effect of intraplantar loperamide (150 μg/15 μL) in SNL rats at 45 min, but not 10 min, post-injection was blocked by pretreatment with an intraplantar injection of naltrexone (75 μg/10 μL); (5) systemic (3.0 mg/kg) and local (150 μg) loperamide reduced the exaggerated duration of hind paw elevation to noxious pinprick stimuli in SNL rats. Intraplantar injection of loperamide also decreased the frequency of pinprick-evoked response in naïve rats.
  
  
  CONCLUSIONS
  These findings suggest that both systemic and local administration of loperamide induce an opioid receptor-dependent inhibition of heat and mechanical hyperalgesia in nerve-injured rats, but that local paw administration of loperamide also induces thermal and mechanical antinociception.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chung
authors.forename: A F
authors.initials: AF
authors.lastname: Carteret
authors.forename: A D
authors.initials: AD
authors.lastname: McKelvy
authors.forename: M
authors.initials: M
authors.lastname: Ringkamp
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: T V
authors.initials: TV
authors.lastname: Hartke
authors.forename: X
authors.initials: X
authors.lastname: Dong
authors.forename: S N
authors.initials: SN
authors.lastname: Raja
authors.forename: Y
authors.initials: Y
authors.lastname: Guan
mesh_terms: D000698:Analgesia / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008139:Loperamide / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D009270:Naloxone / Q000627:therapeutic use; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries*
chemical_list: D000700:Analgesics; D009270:Naloxone; D008139:Loperamide