Elsevier

Journal of Neuroscience Methods

Volume 253, 30 September 2015, Pages 110-115
Journal of Neuroscience Methods

Basic neuroscience
Reliable estimation of nociceptive withdrawal reflex thresholds

https://doi.org/10.1016/j.jneumeth.2015.06.014Get rights and content

Highlights

  • Withdrawal reflex thresholds can often not be estimated using sural nerve stimulation.

  • A lower failure-rate may be obtained by eliciting the reflex at the arch of the foot.

  • Electrical stimulation at the arch enables more reliable reflex threshold estimation.

Abstract

Background

Assessment of the nociceptive withdrawal reflex (NWR) is frequently applied to probe the excitability level of the spinal nociceptive circuitry. In humans, the NWR threshold (NWR-T) is often estimated by applying electrical stimulation over the sural nerve at the lateral malleolus. Such stimulation may be associated with substantial pain and discomfort rendering completion of the assessment infeasible.

New method

As an alternative to sural nerve stimulation, NWR-Ts were also estimated by electrical stimulation at the arch of the foot. Failure-rates and test–retest reliability of these two procedures were evaluated. A fully-automated interleaved up-down staircase procedure was used to estimate the NWR-T for both stimulation sites. NWRs were detected from EMG measured over the biceps femoris and tibialis anterior muscles, respectively. A total of three repeated measures were performed in two different sessions to evaluate the test–retest reliability of the two methods using Bland–Altman agreement analysis.

Results

The failure rate of NWR-T estimation based on electrical stimulation of the sural nerve (29%) was substantially higher than when the NWR was elicited by stimulation at the arch of the foot (5%).

Comparison with existing method

The analysis of test–retest reliability indicated that the two methods for NWR-T estimation were equally reliable for within-session comparisons, but stimulation at the arch of the foot enabled NWR-T estimation with superior between-session reliability

Conclusions

These results support a paradigm shift within NWR-T estimation favoring stimulation at the arch of the foot.

Introduction

The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex responsible for moving the limbs away from potentially harmful stimuli (Sandrini et al., 2005). There exists a close correlation between the NWR and experienced pain (Willer, 1977). Several independent investigations have provided evidence for NWR facilitation in patients with various pain conditions involving central mechanisms leading to increased neuronal responsiveness (Banic et al., 2004, Biurrun Manresa et al., 2013, Courtney et al., 2009, Desmeules et al., 2003, Lim et al., 2011, Lim et al., 2012, Neziri et al., 2010, Sandrini et al., 2006, Sterling et al., 2008). This indicates that the NWR threshold (NWR-T) constitute a valid measure of the excitability level of the spinal nociceptive system.

In humans, the NWR is generally elicited by electrical stimulation of the sural nerve at the lateral malleolus and measured with surface EMG recorded over the ipsilateral brevis head of the biceps femoris muscle (Sandrini et al., 2005). However, the electrical stimulation applied directly over the sural nerve is often associated with substantial pain and discomfort. In both healthy volunteers and pain patients, a number of subjects find the painful stimulation intolerable and the assessment cannot be completed (Banic et al., 2004, Biurrun Manresa et al., 2014b, Sterling et al., 2008). In this way, the practical applicability of the NWR-T as a clinical measure of nociceptive excitability is reduced. Another concern related to this assessment methodology regards the reliability of the obtained measurements. Previous studies investigating the reliability of the NWR-T reported excellent within-session reliability but larger variability between sessions (Biurrun Manresa et al., 2011, Micalos et al., 2009) and it has been suggested that the variability may be caused to some extent by slight inconsistencies in electrode placement resulting in variation in neural activation by the electro-cutaneous stimulation over the sural nerve.

Methods for quantification of reflex receptive fields involve elicitation of the NWR by electrical stimulation applied to the skin under the sole of the foot and measurement of the NWR by surface electromyography (EMG) over the tibialis anterior muscle (Neziri et al., 2009). To most subjects, this procedure is more tolerable than sural nerve stimulation, increasing the likelihood of successful NWR-T estimation. Furthermore, it is hypothesized that stimulation of free nerve endings in the skin at the arch of the foot (the most sensitive area) is less prone to variations in electrode placement than transcutaneous stimulation applied directly over the sural nerve trunk. If so, this may result in a more reliable NWR-T assessment.

The present study investigates the practical applicability of the two methods for NWR-T estimation by evaluating the frequency with which each method fails to yield a successful NWR-T estimation and by examining the test–retest reliability of the two procedures.

Section snippets

Subjects

Twenty one healthy volunteers (age: 18–35 years, 16 females) participated in the study. Written informed consent was obtained from all subjects prior to participation and the Declaration of Helsinki was respected. The study was approved by the local ethical committee (approval number VN—20130006).

Experimental procedure

Two individual estimations of the NWR-T were performed by applying electrical stimulation over the sural nerve and under the sole of the foot, respectively (Fig. 1). An automated staircase procedure

Results

In 6 out the 21 subjects (29%), the NWR-T could not be estimated in at least one of the three repeated measures when the electrical stimulation was applied over the sural nerve (the NWR-T estimation was unsuccessful in 16% of all assessments). For these subjects, the level of electrical stimulation became intolerable and the assessment was terminated. This was only the case in one subject (5%) when applying the stimulation at the arch of the foot (the NWR-T estimation was unsuccessful in less

Discussion

The present study investigated the practical applicability of two methods for NWR-T estimation eliciting the NWR by electrical stimulation applied over the sural nerve and at the arch of the foot, respectively. A focal point of the investigation was the subjective sensation experienced by the test subjects, because stimulation intensities that reach individual tolerance thresholds result in unsuccessful NWR-T estimation. Furthermore, the evaluation was based on examination of test–retest

Conclusion

The present study investigates the practical applicability of two methods for NWR-T estimation involving electrical stimulation applied respectively over the sural nerve trunk and at the arch of the foot. In 29% of the subjects the NWR-T could not consistently be estimated using sural nerve stimulation due to intolerable pain sensations. This was only the case for one subject (5%) when the NWRs were elicited by stimulation at the arch of the foot. Furthermore, NWR-T estimation involving sural

Conflict of interest statement

The authors report no conflict of interest.

Acknowledgment

This work was supported by Danish National Research Foundation grant DNRF121.

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