Name: a quantitative sensory testing paradigm to obtain measures of pain processing in patients undergoing breast cancer surgery
Uploaded: 2018-01-18T15:00:00
Description: Watch this Scientific Journal Video about A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery at JoVE.com

We thank the patients who participated in the study presented in the &#39;Representative results&#39; section.

This protocol has been approved in the context of a previous randomized controlled trial8 by the human research ethics committee region Arnhem-Nijmegen, the Netherlands (nr. 2004/239).
1. Preparation for Testing
<ol>
	<li>Informed consent:
	<ol>
		<li>Review the informed consent form together with the patient.</li>
		<li>Answer any questions that patient may have regarding the study.</li>
		<li>Obtain written informed consent by having the patient sig...

<ol>
	<li>Macrae, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+post-surgical+pain:+10+years+on.">Chronic post-surgical pain: 10 years on.</a> Br J Anaesth. 101 (1), 77-86 (2008).</li><li>IASP Taxonomy Working Group. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Classification of Chronic Pain. , (2011).</li><li>Kehlet, H., Jensen, T. S., Woolf, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+postsurgical+pain:+risk+factors+and+prevention.">Persistent postsurgical pain: risk factors and prevention.</a> Lancet. 367 (9522), 1618-1625 (2006).</li><li>Steegers, M. A., Wolters, B., Evers, A. W., Strobbe, L., Wilder-Smith, O. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+axillary+lymph+node+dissection+on+prevalence+and+intensity+of+chronic+and+phantom+pain+after+breast+cancer+surgery.">Effect of axillary lymph node dissection on prevalence and intensity of chronic and phantom pain after breast cancer surgery.</a> J Pain. 9 (9), 813-822 (2008).</li><li>Yarnitsky, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+of+chronic+post-operative+pain:+pre-operative+DNIC+testing+identifies+patients+at+risk.">Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.</a> Pain. 138 (1), 22-28 (2008).</li><li>Hsu, E., Cohen, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Postamputation+pain:+epidemiology,+mechanisms,+and+treatment.">Postamputation pain: epidemiology, mechanisms, and treatment.</a> J Pain Res. 6, 121-136 (2013).</li><li>Franneby, U., Sandblom, G., Nordin, P., Nyren, O., Gunnarsson, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risk+factors+for+long-term+pain+after+hernia+surgery.">Risk factors for long-term pain after hernia surgery.</a> Ann Surg. 244 (2), 212-219 (2006).</li><li>van Helmond, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperalgesia+and+Persistent+Pain+after+Breast+Cancer+Surgery:+A+Prospective+Randomized+Controlled+Trial+with+Perioperative+COX-2+Inhibition.">Hyperalgesia and Persistent Pain after Breast Cancer Surgery: A Prospective Randomized Controlled Trial with Perioperative COX-2 Inhibition.</a> PLoS One. 11 (12), e0166601 (2016).</li><li>Le Bars, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+whole+body+receptive+field+of+dorsal+horn+multireceptive+neurones.">The whole body receptive field of dorsal horn multireceptive neurones.</a> Brain Res Brain Res Rev. 40 (1-3), 29-44 (2002).</li><li>Yarnitsky, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+on+practice+of+conditioned+pain+modulation+(CPM)+testing.">Recommendations on practice of conditioned pain modulation (CPM) testing.</a> Eur J Pain. 19 (6), 805-806 (2015).</li><li>Rolke, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+sensory+testing:+a+comprehensive+protocol+for+clinical+trials.">Quantitative sensory testing: a comprehensive protocol for clinical trials.</a> Eur J Pain. 10 (1), 77-88 (2006).</li><li>Wilder-Smith, O. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> A Paradigm-Shift in Pain Medicine: Implementing a Systematic Approach to Altered Pain Processing in Everyday Clinical Practice. Based on Quantitative Sensory Testing. , (2013).</li><li>Nasri-Heir, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+pain+modulation+in+patients+with+persistent+postendodontic+pain.">Altered pain modulation in patients with persistent postendodontic pain.</a> Pain. 156 (10), 2032-2041 (2015).</li><li>Treede, R. D., Meyer, R. A., Raja, S. N., Campbell, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Peripheral+and+central+mechanisms+of+cutaneous+hyperalgesia.">Peripheral and central mechanisms of cutaneous hyperalgesia.</a> Prog Neurobiol. 38 (4), 397-421 (1992).</li></ol>

Our method of quantifying pressure pain thresholds, electrical pain thresholds, and CPM can be successfully applied in a clinical context given its short duration (~20 minutes). We have previously shown that pressure pain values obtained early after surgery may be of value in predicting persistent pain at long term follow-up in the context of breast cancer surgery8. While electrical pain thresholds CPM were not predictive of persistent pain in our study, others have shown that these measures may b...

Chronic pain following surgery, persistent postsurgical pain, is an important condition contributing to significant symptom burden and lower quality of life1. Persistent post-surgical pain remains poorly understood, but is broadly recognized as pain lasting more than 3 months after surgery2. The condition is common, with estimates of its prevalence ranging from 10% to 50% of all postsurgical patients3. High-risk procedures include breast surgery4, thoracotomy5, limb amputation6, and hernia repair7. Persistent postsurgical pain is relatively refractory to treatment and thus has generated interest in potential preventive strategies and treatments. A better understanding of predicting and characterizing persistent postoperative pain would help identify the subset of patients who are likely to require additional treatment to optimize their peri-operative pain management.
Recently it was shown that abnormal changes in pain thresholds in response to surgery may be of predictive value for long-term persistent pain development in the context of surgery for breast cancer8. Others have stressed the importance of the conditioned pain modulation (CPM) effect in predicting persistent postoperative pain, for example with regards to persistent pain after thoracotomy5. CPM is the behavioral correlate of diffuse noxious inhibitory control, a physiological phenomenon where input from peripheral c-fibers results in diffuse inhibition from the brainstem of all incoming stimuli mediated by c-fiber from heterotopic fields9. The CPM effect is measured by comparing thresholds to a noxious stimulus, which is measured before and after the application of a second different stimulus, which is referred to as the conditioning stimulus10.
Current standardized quantitative sensory testing (QST) protocols, such as the German Research Network on Neuropathic Pain protocol11 are quite extensive and may not be suitable to perform in surgical patients. The aim of the current publication is to detail a short and standardized protocol to obtain both pain thresholds and a CPM effect measurement in breast cancer surgery patients. This protocol is derived from a collaborative protocol between our university and the University of Aalborg, Denmark12.

<table>
	<tbody>
		<tr>
			<td>Bed</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of hospital bed or medical exam table</td>
		</tr>
		<tr>
			<td>Desk</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available desk</td>
		</tr>
		<tr>
			<td>Office chair</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available office chair</td>
		</tr>
		<tr>
			<td>Force FPX 50 Pressure algometer</td>
			<td>Wagner Instruments, Greenwich, CT, USA</td>
			<td>N/A</td>
			<td>Pressure algometer with a 1.0 cm2 circular tip to deliver pressure to perform pressure pain threshold measurements</td>
		</tr>
		<tr>
			<td>Desktop computer</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available Windows computer to run QST-IV Stimulus Manager software on to control the QST-IV stimulator</td>
		</tr>
		<tr>
			<td>QST-IV Stimulus Manager</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>Software to control the settings of QST-IV electrical stimulator</td>
		</tr>
		<tr>
			<td>QST-IV Electrical Stimulator</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>Electrical quantitative sensory testing device with a patient operated switch. Device used to deliver electrical current to perform the electrical threshold measurements</td>
		</tr>
		<tr>
			<td>VAS Slider</td>
			<td>Embedded Control BV, Ruurlo, the Netherlands</td>
			<td>N/A</td>
			<td>The VAS slider consists of a box with a mobile lever on a horizontal bar that represents the VAS and is connected to the QST-IV.</td>
		</tr>
		<tr>
			<td>Kendall H34SG 50 x 45 mm</td>
			<td>Covidien, Mansfield, USA</td>
			<td>N/A</td>
			<td>Self-adhesive skin electrodes to apply to the measurement points on the skin to deliver electrical stimualtion</td>
		</tr>
		<tr>
			<td>Crushed Ice</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Ice generated by ice machine to cool water sufficiently for the cold pressor test</td>
		</tr>
		<tr>
			<td>Bucket</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available 10 L bucket</td>
		</tr>
		<tr>
			<td>Surgical skin marker</td>
			<td>Covidien, Mansfield, USA</td>
			<td>N/A</td>
			<td>Any type of commercially available surgical skin marker</td>
		</tr>
		<tr>
			<td>Stopwatch</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available stopwatch</td>
		</tr>
		<tr>
			<td>Measurement form</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Score form provided in the manuscript</td>
		</tr>
		<tr>
			<td>Pencil</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available pencil</td>
		</tr>
		<tr>
			<td>Thermometer</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Thermometer to measure water temperature of ice water</td>
		</tr>
		<tr>
			<td>Ruler</td>
			<td>N/A</td>
			<td>N/A</td>
			<td>Any type of commercially available ruler</td>
		</tr>
	</tbody>
</table>

a quantitative sensory testing paradigm to obtain measures of pain processing in patients undergoing breast cancer surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

In a previously published clinical trial in women (N = 94) undergoing surgery for breast cancer, we measured electrical and pressure pain thresholds as well as CPM using the protocol described in this report8. We performed the testing paradigm pre-operatively and at various time points throughout the year following surgery. We found that women who developed persistent postsurgical pain 12 months after breast cancer surgery, defined as a VAS of &#62;30 mm, ...

Watch this Scientific Journal Video about A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery at JoVE.com

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

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