title: Long-term effect of epidural injection with sustained-release lidocaine particles in a rat model of postoperative pain.
abstract: BACKGROUND
  Single applications of sustained-release local anaesthetics may provide prolonged pain relief without requiring indwelling catheters, but have not yet been investigated for epidural postoperative pain management. We synthesized injectable sustained-release lidocaine particles (SRLPs) from biodegradable polymers and examined their effect in a rat model of postoperative pain.
  
  
  METHODS
  Two types of polylactic acid particles, SRLP-10 and SRLP-25, containing 10% or 25% lidocaine, respectively, were generated and the lidocaine release was evaluated in vitro for 14 days. The SRLPs were then injected epidurally in the male Sprague-Dawley rats immediately before they received a hindpaw incision (the postoperative pain model), and hindpaw hypersensitivity was evaluated with the von Frey test. Motor paralysis and coordination were also assessed using a paralysis score and rota-rod test. Neurotoxicity and inflammation of the spinal cord, cauda equina, and tissue surrounding the injection site were histologically evaluated.
  
  
  RESULTS
  In vitro, SRLP-10 and SRLP-25 released lidocaine over 7 and 3 days, respectively. The in vivo injection of SRLP-10 (80 mg) produced anti-hypersensitivity with no evidence of motor paralysis for 7 days after the paw incision, and SRLP-25 (60 mg) inhibited postoperative hypersensitivity for 7 days. Temporary motor paralysis (15 min) was observed after the injection of SRLP-25 (even with 40 mg). Foreign body reactions were observed around the SRLP injection site at 1 and 4 weeks after injection. No histopathological changes were observed at 1 or 4 weeks.
  
  
  CONCLUSIONS
  The epidural injection of SRLPs produced prolonged anti-hypersensitivity in a rat model of postoperative pain with no major complications.
authors.affiliation: Department of Anesthesiology and.
authors.forename: T
authors.initials: T
authors.lastname: Suto
authors.forename: H
authors.initials: H
authors.lastname: Obata
authors.forename: M
authors.initials: M
authors.lastname: Tobe
authors.forename: H
authors.initials: H
authors.lastname: Oku
authors.forename: H
authors.initials: H
authors.lastname: Yokoo
authors.forename: Y
authors.initials: Y
authors.lastname: Nakazato
authors.forename: S
authors.initials: S
authors.lastname: Saito
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007268:Injections, Epidural; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D010147:Pain Measurement / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013995:Time
chemical_list: D000779:Anesthetics, Local; D003692:Delayed-Action Preparations; D008012:Lidocaine