Intraperitoneally Administered Lidocaine Attenuates Thermal Allodynia in a Murine “Two-Hit” Chronic Constriction Injury Model

Selina E I Van Der Wal,Michiel Vaneker,Monique A H Steegers,Lisa Cornelissen,Kris C P Vissers,Sandra A S Van Den Heuvel,Gert-Jan Scheffer

doi:10.4236/ojas.2016.63028

Abstract

Background: Mechanical ventilation (hit one) during surgery (hit two) is often needed and both induce an inflammatory response. Dysregulation of the inflammatory response can cause chronic postoperative pain. Methods: Healthy C57BL6 mice (n = 56) were mechanically ventilated (MV) and allocated to receive sham (MV-sham) or mechanically ventilation with chronic constriction injury (MV-CCI) surgery in the left hind paw. Plasma interleukin (IL)-1β, IL-6, IL-10, keratinocyte derived chemokine (KC) and tumor necrosis factor (TNF)-α were determined on day 0 and 16. Sensory testing was performed on day 0, 3, 7 and 16 by cold plate test (number of lifts (NOL) and cumulative reaction time (CRT)) and von Frey test. The effect of lidocaine on cytokines and sensory testing was analyzed. Results: MV-Sham showed an increase in IL-1β and TNF-α, and MV- CCI-lido increased levels of KC compared with MV on day 0. No difference in cytokine levels was observed on day 16. NOL of the left paw versus the right was increased in MV-CCI on day 7, and in MV-CCI-lido on day 7 and 16. The NOL of the left paw was decreased in MV-sham and MV-CCI-lido compared with MV-CCI on day 16. The CRT of the left paw was increased for MV-CCI on day 3 and 7, and for MV-CCI-lido on day 7. On day 16, MV-sham and MV-CCI-lido showed a decreased CRT of the left paw compared with MV-CCI. Conclusion: Nerve injury and not systemic inflammatory response seems mandatory for development of neuropathic pain in this “two-hit” model. Lidocaine attenuates cold allodynia in mice.

Highlights

Several studies have been investigating “two-hit” models in trauma or surgical patients [1]
In part 2 (n = 24), we investigated in mechanically ventilated (MV)-sham (n = 8), mechanically ventilation with chronic constriction injury (MV-constriction injury (CCI)) (n = 8) and MV-CCI-lido (n = 8) the effect of low dose lidocaine on the development of neuropathic pain with postoperative sensory testing on day 3, 7 and 16 and measured the inflammatory response on day 16 (Figure 2)
We observed some hiccupping during monoanesthesia with isoflurane and a somewhat longer recovery time compared with previous experiments where we performed CCI in spontaneous breathing mice

Summary

Introduction

Several studies have been investigating “two-hit” models in trauma or surgical patients [1]. The severity of injury seems to correlate with the inflammatory response [4] [5] involving interleukin (IL)-6, IL-1, IL-8 and tumor necrosis factor α (TNF-α) [5]. Mechanical ventilation (MV) without surgery can result in an inflammatory response, characterized by release of inflammatory cytokines and influx of immune cells such as neutrophils [7]-[10]. Results: MV-Sham showed an increase in IL-1β and TNF-α, and MVCCI-lido increased levels of KC compared with MV on day 0. The NOL of the left paw was decreased in MV-sham and MV-CCI-lido compared with MV-CCI on day 16. On day 16, MV-sham and MV-CCI-lido showed a decreased CRT of the left paw compared with MV-CCI. Conclusion: Nerve injury and not systemic inflammatory response seems mandatory for development of neuropathic pain in this “two-hit” model.

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Conclusion