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Sustained analgesic effect of clonidine co-polymer depot in a porcine incisional pain model

Authors Wilsey JT, Block JH

Received 14 November 2017

Accepted for publication 26 January 2018

Published 9 April 2018 Volume 2018:11 Pages 693—701

DOI https://doi.org/10.2147/JPR.S157018

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Minal Joshi

Peer reviewer comments 3

Editor who approved publication: Dr E Alfonso Romero-Sandoval


Jared T Wilsey, Julie H Block

Medtronic Spine Division, Memphis, TN, USA

Background: Previous research suggests that the α2 adrenergic agonist clonidine, a centrally acting analgesic and antihypertensive, may also have direct effects on peripheral pain generators. However, aqueous injections are limited by rapid systemic absorption leading to off target effects and a brief analgesic duration of action.
Purpose: The aim of this study was to examine the efficacy of a sustained-release clonidine depot, placed in the wound bed, in a pig incisional pain model.
Methods: The depot was a 15 mm ×5 mm ×0.3 mm poly(lactide-co-caprolactone) polymer film containing 3% (w/w) clonidine HCl (MDT3). Fifty-two young adult mix Landrace pigs (9–11 kg) were divided into seven groups. All subjects received a 6 cm, full-thickness, linear incision into the left lateral flank. Group 1 served as a Sham control group (Sham, n=8). Group 2 received three placebo strips (PBO, n=8), placed end-to-end in the subcutaneous wound bed before wound closure. Group 3 received one MDT3 and two PBO (n=8), Group 4 received two MDT3 and one PBO (n=8), and Group 5 received three MDT3 (n=8). Positive control groups received peri-incisional injections of bupivacaine solution (Group 6, 30 mg/day bupivacaine, n=8) or clonidine solution (Group 7, 225 µg/day, n=4).
Results:
The surgical procedure was associated with significant peri-incisional tactile allodynia. There was a dose-dependent effect of MDT3 in partially reversing the peri-incisional tactile allodynia, with maximum pain relief relative to Sham at 72 hours. Daily injections of bupivacaine (30 mg), but not clonidine (up to 225 µg), completely reversed allodynia within 48 hours. There was a statistically significant correlation between the dose of MDT3 and cumulative withdrawal threshold from 4 hours through the conclusion of the study on day 7.
Conclusion: These data suggest that a sustained-release clonidine depot may be a viable nonopioid, nonamide anesthetic therapy for the treatment of acute postsurgical nociceptive sensitization.

Keywords: amide anesthetic, bio-erodible polymer, peripherally acting analgesic, imidazoline, porcine model, postoperative pain, regional anesthesia, sustained release

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