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Bortolami, Elisa (2015) Advances in sheep analgesia. [Tesi di dottorato]

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Abstract (inglese)

Sheep (Ovis aries) are widely used in experimental settings and breeding system, nevertheless pain treatment in this species seems to be overlooked.
The first two studies described in this thesis were designed to evaluate administration of analgesics both in the experimental and clinical setting. The third study evaluated the pharmacokinetics and antinociceptive effects of tramadol and its metabolite O-desmethyltramadol (M1) in sheep in a preclinical model of pain.
The first study consisted of a meta-analysis of the reported use of analgesics in sheep for experimental purposes. Studies involving experimental procedures in sheep carried out in selected years (2008-2011-2014) were identified using a search engine. A total of 75 papers were selected. The study showed that analgesic treatment was often not accurately reported.
The second study consisted of an on-line questionnaire evaluating the current attitudes of Italian practitioners to assessment and treatment of pain in sheep. The questionnaire consisted of five sections regarding the demographic data, analgesic drugs and techniques used to treat pain, attitudes to pain relief and assessment of pain and the knowledge on the topic of sheep analgesia. Only a modest number of questionnaires were returned. The most commonly used drugs by sheep practitioners who replied to the questionnaire were non steroidal anti-inflammatory drugs and local anaesthetics. In the practitioners’ opinion the main reasons for analgesic drugs not to be administered to sheep was the lack of licensed drugs followed by costs, withholding times and regulations. The vast majority of practitioners were interested in improving their knowlwdge on sheep analgesia.
The third study investigated the pharmacokinetic profile and antinociceptive effect of tramadol and M1 following intravenous administration in sheep. Six healthy adult sheep were administered 4 (T4) and 6 (T6) mg/kg of tramadol (T) and saline (SAL) over 2 minutes in a cross over design with a two weeks wash out period. At predetermined time points blood samples were collected, physiological parameters and mechanical nociceptive threshold (NMT) values were recorded. Tramadol and M1 fitted a two compartmental model and a non compartmental model respectively. Pharmacokinetic parameters were similar for T4 and T6. Tramadol and M1 plasma concentrations decreased rapidly. Physiological parameters were not statistically different between groups. No mechanical antinociceptive effects of tramadol were detected, as MNT values did not statistically differ between groups.
In conclusion, these studies showed that there is great scope for improvement in pain assessment and treatment in sheep both in the research than clinical settings. Moreover more experimental and clinical studies regarding the pharmacokinetic and pharmacokinamic effects of analgesic drugs in sheep are advocated in order to improve their welfare.

Abstract (italiano)

La pecora domestica (Ovis aries) è una delle specie animali più comunemente allevate ed utilizzate nella ricerca biomedica; nonostante questo l’analgesia in questo animale è stata a lungo trascurata.
I primi due studi presentati in questa tesi sono stati elaborati allo scopo di valutare la somministrazione di analgesici nell’ambito clinico e sperimentale. Il terzo studio valuta la farmacocinetica e gli effetti antinocicettivi del tramadolo e del suo metabolita O desmethyltramadol (M1).
Il primo studio consiste in una meta-analisi sull’ uso di farmaci analgesici riportato nelle pecore utilizzate a fini sperimentali. Studi riguardanti procedure sperimentali in pecore effettuati in anni selezionati (2008-2011-2014) sono stati identificati utilizzando un motore di ricerca. In totale, sono stati selezionati 75 articoli scientifici. Lo studio evidenzia mostra che la terapia antalgica spesso non viene accuratamente riportata.
Il secondo studio consiste in un questionario on line redatto allo scopo di valutare l’attuale approccio dei veterinari italiani, che si occupano della specie ovina, alla valutazione ed al trattamento del dolore in questa specie. Il questionario era diviso in cinque sezioni riguardanti i dati demografici, l’uso di farmaci analgesici a tecniche utilizzate per apportare analgesia, e l’approccio utilizzato dai veterinari nella valutazione e trattamento del dolore nella specie ovina, ed, infine, la loro conoscenza riguardo tale argomento. Un numero limitato di veterinari ha completato il questionario. I farmaci più comunemente utilizzati dai veterinari che hanno risposto al questionario sono i farmaci antiinfiammatori non steroidei e gli anestetici locali. Secondo l’opinione dei veterinari, le ragioni principali per cui la terapia analgesica non viene effettuata nella specie ovina erano la mancanza di farmaci registrati, il loro costo, i tempi di sospensione e la regolamentazione riguardante il loro utilizzo. La maggior parte dei veterinari si dimostrava interessata a migliorare le proprie conoscenze riguardo l’analgesia nella specie ovina.
Il terzo studio investiga la farmacocinetica e gli effetti antinocicettivi del tramadolo ed M1 dopo somministrazione endovenosa nelle pecore. Due dosi di tramadolo, 4 mg/kg (T4) e 6 mg/kg (T6), e soluzione salina (SAL) sono state somministrate in due minuti a sei pecore adulte e sane in uno studio randomizzato “in cieco” con un periodo di sospensione di due settimane. A tempi predeterminati, sono stati effettuati i prelievi di sangue per l’analisi farmacocinetica, e sono stati registrati i parametri fisiologici e i valori dopo stimolazione nocicettiva meccanica (MNT). Tramadolo ed M1 presentano rispettivamente una cinetica bi-compartimentale e non-compartimentale. I parametri farmacocinetici sono simili per le due dosi T4 e T6. Le concentrazioni plasmatiche di tramadolo ed M1 sono rapidamente diminuite. I parametri fisiologici non sono risultati statisticamente diversi tra i gruppi. Non sono stati evidenziati effetti antinociettivi del tramadolo; infatti i valori di MNT non sono risultati statisticamente diversi tra i gruppi.
Concludendo, questi studi hanno dimostrato che ci sono ampi margini di miglioramento nella valutazione e trattamento del dolore nella specie ovina sia in ambito sperimentale sia clinico. Inoltre, sono necessari studi sperimentali e clinici riguardanti la farmacocinetica e farmacodinamica di farmaci analgesici nella specie ovina al fine di migliorarne il benessere.

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Tipo di EPrint:Tesi di dottorato
Relatore:De Benedictis, Giulia Maria
Dottorato (corsi e scuole):Ciclo 27 > scuole 27 > SCIENZE VETERINARIE
Data di deposito della tesi:20 Luglio 2015
Anno di Pubblicazione:20 Luglio 2015
Parole chiave (italiano / inglese):pecora, analgesia, tramadolo, farmacocinetica, chirurgia sheep, analgesia, tramadol, pharmacokinetics, surgery
Settori scientifico-disciplinari MIUR:Area 07 - Scienze agrarie e veterinarie > VET/09 Clinica chirurgica veterinaria
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Animale, Produzioni e Salute
Codice ID:8854
Depositato il:25 Ago 2016 11:48
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