@article {Garcia2010a,
	title = {{Analgesic and antiallodynic effects of antidepressants after infiltration into the rat.}},
	journal = {Pharmacology},
	volume = {86},
	number = {4},
	year = {2010},
	month = {jan},
	pages = {216{\textendash}23},
	abstract = {Tricyclic antidepressants (TCA) have potent local anesthetic properties and may produce a long-lasting pain blockade that could be of interest in relieving chronic pain states such as neuropathic pain, but there are only few data comparing their dose-response curves of analgesic activity under the same experimental conditions. This study examines the time course of pain-relieving properties of 7 TCA in heat-induced paw withdrawal after subcutaneous administration. Mixed inhibitors of norepinephrine and serotonin uptake (amitriptyline, nortriptyline, imipramine, desipramine, doxepin) and selective inhibitors of serotonin uptake (fluoxetine and fluvoxamine) were assayed. The TCA with the longest analgesic activity were selected to test its antiallodynic effect in the neuropathic pain model of chronic sciatic nerve constriction injury. Bupivacaine was used as a reference drug in both experiments. A dose versus time of maximal analgesic effect curve was constructed for each drug. The longest analgesic effect was obtained for doxepin and imipramine. Although low doses of amitriptyline showed the same activity than doxepin, higher doses failed to reach the same effect. Selective inhibitors of serotonin showed no action at all doses tested. In the chronic sciatic nerve constriction injury model, doxepin and, to a smaller degree, amitriptyline and imipramine protected from allodynia; bupivacaine was ineffective. The antiallodynic effect always lasted less long than the analgesic effect. These observations provide support for the potential use of TCA as durable analgesics. Doxepin overall showed the most outstanding results in pain relief.},
	keywords = {Adrenergic Uptake Inhibitors, Adrenergic Uptake Inhibitors: administration \& dos, Adrenergic Uptake Inhibitors: pharmacology, Analgesics, Analgesics: administration \& dosage, Analgesics: pharmacology, Anesthetics, Animal, Animals, Antidepressive Agents, Bupivacaine, Bupivacaine: pharmacology, Disease Models, Dose-Response Relationship, Drug, Hyperalgesia, Hyperalgesia: drug therapy, Local, Local: pharmacology, Male, Pain, Pain: drug therapy, Rats, Sciatic Neuropathy, Sciatic Neuropathy: drug therapy, Serotonin Uptake Inhibitors, Serotonin Uptake Inhibitors: administration \& dosa, Serotonin Uptake Inhibitors: pharmacology, Sprague-Dawley, Time Factors, Tricyclic, Tricyclic: administration \&, Tricyclic: pharmacology},
	issn = {1423-0313},
	doi = {10.1159/000319747},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-77956380582\&partnerID=tZOtx3y1},
	author = {Garcia, Xavier and del Valle, Jaume and Escribano, Elvira and Domenech, Josep and Queralt, Josep}
}
@article {Garcia2010,
	title = {{In vitro characterization and in vivo analgesic and anti-allodynic activity of PLGA-bupivacaine nanoparticles}},
	journal = {Journal of Nanoparticle Research},
	volume = {13},
	number = {5},
	year = {2010},
	month = {jun},
	pages = {2213{\textendash}2223},
	abstract = {An injectable controlled release system containing local anesthetics able to provide longlasting analgesia in nociceptive and neuropathic pain could have a marked impact in pain management. In order to address this issue, bupivacaine, a widely used local anesthetic, has been nanoencapsulated using poly(lactic-co-glycolic acid) from an oil-in-water emulsion by the solvent evaporation technique. Nanoparticles were evaluated in vitro studying their drug release mechanism by fitting different model equations, and in vivo by testing its analgesic and anti-allodynic activity in front of heat-induced nociceptive pain and sciatic nerve chronic constriction injury in rats, respectively. The particle size of the PLGA nanoparticles obtained was of 453 {\textpm} 29 nm, the encapsulation efficiency, drug loading, and burst effect at 30 min were 82.10 {\textpm} 0.001, 45.06 {\textpm} 0.001, and 4.6 {\textpm} 0.6\%, respectively. A prolonged release of the drug in comparison to bupivacaine solution was seen. The mean dissolution time (MDT) obtained for nanoparticles was relatively long (9.44 {\textpm} 0.56 h) proving the sustained release process, while the dissolution efficiency (DE) (84.10 {\textpm} 1.01\%) was similar to the maximum percentage of drug released. Korsmeyer- Peppas was the best model that fitted our release data.A non-Fickian mechanism was concluded to be involved in the release of bupivacaine from the nanoparticles, taking into account the value of the diffusional exponent obtained (n = 0.95). After local infiltration in the rat, the antinociceptive and anti-allodynic activity of the nanoencapsulated bupivacaine was longer lasting than that of bupivacaine solution. An increase in the values of the area under the curve (AUC) of the antinociceptive and anti-allodynic effect versus time of 67 and 36\%, respectively, was observed when the drug was encapsulated. {\textcopyright} Springer Science+Business Media B.V. 2010.},
	keywords = {Antiallodynia, Antinociception, Bupivacaine, In vitro release, Korsmeyer-peppas, Modeling and simulation, Nanomedicine, Plga nanoparticles},
	issn = {1388-0764},
	doi = {10.1007/s11051-010-9979-1},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-79956290523\&partnerID=tZOtx3y1},
	author = {Garcia, Xavier and Escribano, Elvira and Domenech, Josep and Queralt, Josep and Freixes, Joan}
}
