Sensory Abnormalities in Post-surgical Peripheral Neuropathy

NCT03966677 | Completed DMC

• 1 other identifier: H-16034340
• Study Type: observational
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

The concept of normality is a cornerstone in medical practice and research. As an example, in clinical chemistry, a laboratory value based on a plasma sample exceeding the +/- 1.96 x standard deviation (SD) range, referenced from normative material, is, per definition, outside the normal range (the reference interval). Obviously, a number of reasons for this deviation may exist. The sample value could reflect a "true" pathological condition but could also be caused by error, e.g., technical measurement error, drug-interaction error, random error, or reflect a value occurring in 5% of the healthy population. Conversely, a sample value in the normal range evidently does not exclude a pathological condition. The reference interval is calculated from a large number of healthy subjects sampled across age, anthropometrics, ethnicity, and gender. Normative reference intervals are certainly of help, particularly in the screening of subjects, but may be of limited value in the detailed assessment of pathophysiological processes. Also, increasing the number of analyses in a subject expands the risk of making a type I error (acquiring "false" positive results). The likelihood of one or more type I errors in the analysis of 10 different laboratory values in one subject is impressive 46% (\[1 - 0.95\^10\] =0.46). It is well-known that multiple measurements are commonly performed in medical practice and research, but corrected significance levels are not always used.

Conditions

Chronic Pain

Keywords

Groin hernia repair; Persistent postsurgical pain; Quantitative sensory testing (QST); Normative data

Outcome Measures

Primary Outcomes (6)

• Thermal thresholds

  Warmth detection threshold (WDT), cool detection threshold, heat pain threshold (HPT) and cold pain threshold (CPT) are made by a computerized contact thermode (Thermotest, Somedic AB, Sweden) with an active thermal surface of 12.5 cm\^2 (2.5 x 5.0 cm\^2) as previously described in detail. The thresholds are determined from a baseline temperature of 32°C with a ramp rate of + 1°C/s. Cut-offs for heat and cold are 50°C and 5°C, respectively. The assessments are made in triplicate and the mean values are used in the statistical analyses.

  2019-2023

• Pressure algometry

  Deep-tissue pain sensitivity is assessed using a hand-held pressure algometer with a neoprene-coated tip of area 1.0 cm2 (Somedic AB, Sweden), as previously described. The algometer is applied perpendicularly to the skin with a pressure rate of 30 kPa/s. The study subject is told to report the pressure pain threshold (PPT) by activating the button device when pain is perceived. The cut-off limit is 350 kPa. Testing is done in triplicate and the average value is used in the statistical analyses.

  2019-2023

• Suprathreshold heat stimulation

  A short tonic heat stimulus (heating area 12.5 cm\^2; ramp rate: 1°C/s, plateau: 47°C, 5 s; STH) is delivered in order to evaluate the suprathreshold heat pain perception (NRS).

  2019-2023

• Sensory mapping

  Sensory mapping in the groin areas is assessed with a 25°C metal roll (Somedic AB), moved at a rate of 1 to 2 cm/s from skin with normal cool perception, using an octagonal approach, into the areas in order to indicate sensory changes. Changes in the study subject's cool perception are indicated by a marker on the skin, and subsequently transferred to a transparent sheet for later area assessment in a vector-based drawing drawing program (Canvas 12.0; ACD Systems, Seattle, WA).

  2019-2023

• Tactile thresholds

  Tactile detection thresholds (TDT) and tactile pain threshold (TPT) are determined by polyamide monofilaments (Stoelting, IL, USA; nominal buckling force ranging from 0.04 to 4,400 mN) using a modified Dixon up-and-down method, with 3 descending and 3 ascending stimulus intensities. The filament with the smallest buckling force leading to tactile recognition (TDT) is registered. The tactile pain threshold (TPT) is determined by the same stimulus paradigm, but registering the perception of pain (sharpness/sting; TPT).

  2019-2023

• Temporal summation

  Temporal summation test, i.e., the perception in response to repetitive (0.3 to 3 Hz) mechanical stimulation \[i.e., wind-up like pain: WUP\], indicates presence of central sensitization. The repetitive 1 Hz stimuli for 60 s are either dynamically delivered by a brush or statically delivered by a polyamide filament (one nominal rank below TPT). The study subjects are told to report the level of pain (NRS) every 15 s-1 during the stimulation. Signs of aftersensations are followed 60 s after discontinuation of the stimulation, and the intensity of discomfort or pain is rated by NRS.

  2019-2023

Secondary Outcomes (2)

• Assessments of Anxiety and Depression

  2019-2023

• Assessment of Pain Catastrophizing

  2019-2023

Study Arms (3)

P-GHR

Patients with persistent severe pain after groin hernia repair.

NP-GHR

Patients without pain after groin hernia repair.

NP

Healthy non-operated controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study subjects with pain after GHR (P-GHR) (n=54) Study subjects without pain after GHR (NP-GHR) (n=54) Healthy non-operated study subjects (NP) (n=54)

You may qualify if:

• All study subjects must meet all the following criteria to be eligible to enroll in the study:
• Age above 18 yrs and below 65 yrs
• Signed informed consent
• Body mass index (BMI): 18 \< BMI \< 35 kg/m\^2
• ASA I-II
• In addition, for study subjects without pain after GHR (NP-GHR):
• having undergone uncomplicated, elective, unilateral open GHR a.m. Lichtenstein
• no restriction in ADL-functions due to the GHR
• activity-related groin pain \< 3 (numerical rating scale \[NRS\]: 0 = no pain, 10 = worst imaginable pain)

You may not qualify if:

• do not speak or understand Danish
• who cannot cooperate with the investigation
• abuse of alcohol or drugs - according to investigator's evaluation
• use of psychotropic drugs (exception of SSRI)
• neurologic or psychiatric disease
• chronic pain condition
• regular use of analgesic drugs
• skin lesions or tattoos in the assessment areas (groins, lower arm)
• nerve lesions in the assessment sites (e.g., after trauma, abdominal surgery)
• In addition, for healthy non-operated study subjects (NP):
• subjects, who have had previous surgery in or near the groin region
• use of prescription drugs one week before the trial
• use of over-the-counter (OTC) drugs 48 hours before the trial
• experiencing pain at rest \> 3 (NRS)
• experiencing activity-related pain in or near the groin \> 3 (NRS)

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (1)

Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, Blegdamsvej 9

Copenhagen O, 2100, Denmark

Location

Related Publications (10)

• Schug SA, Lavand'homme P, Barke A, Korwisi B, Rief W, Treede RD; IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD-11: chronic postsurgical or posttraumatic pain. Pain. 2019 Jan;160(1):45-52. doi: 10.1097/j.pain.0000000000001413.

  PMID: 30586070 BACKGROUND

• Treede RD. The role of quantitative sensory testing in the prediction of chronic pain. Pain. 2019 May;160 Suppl 1:S66-S69. doi: 10.1097/j.pain.0000000000001544.

  PMID: 31008852 BACKGROUND

• Reimer M, Forstenpointner J, Hartmann A, Otto JC, Vollert J, Gierthmuhlen J, Klein T, Hullemann P, Baron R. Sensory bedside testing: a simple stratification approach for sensory phenotyping. Pain Rep. 2020 May 21;5(3):e820. doi: 10.1097/PR9.0000000000000820. eCollection 2020 May-Jun.

  PMID: 32903958 BACKGROUND

• Truini A, Aleksovska K, Anderson CC, Attal N, Baron R, Bennett DL, Bouhassira D, Cruccu G, Eisenberg E, Enax-Krumova E, Davis KD, Di Stefano G, Finnerup NB, Garcia-Larrea L, Hanafi I, Haroutounian S, Karlsson P, Rakusa M, Rice ASC, Sachau J, Smith BH, Sommer C, Tolle T, Valls-Sole J, Veluchamy A. Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment. Eur J Neurol. 2023 Aug;30(8):2177-2196. doi: 10.1111/ene.15831. Epub 2023 May 30.

  PMID: 37253688 BACKGROUND

• Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DLH, Bouhassira D, Cruccu G, Freeman R, Hansson P, Nurmikko T, Raja SN, Rice ASC, Serra J, Smith BH, Treede RD, Jensen TS. Neuropathic pain: an updated grading system for research and clinical practice. Pain. 2016 Aug;157(8):1599-1606. doi: 10.1097/j.pain.0000000000000492.

  PMID: 27115670 BACKGROUND

• Pfau DB, Krumova EK, Treede RD, Baron R, Toelle T, Birklein F, Eich W, Geber C, Gerhardt A, Weiss T, Magerl W, Maier C. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): reference data for the trunk and application in patients with chronic postherpetic neuralgia. Pain. 2014 May;155(5):1002-1015. doi: 10.1016/j.pain.2014.02.004. Epub 2014 Feb 10.

  PMID: 24525274 BACKGROUND

• Magerl W, Krumova EK, Baron R, Tolle T, Treede RD, Maier C. Reference data for quantitative sensory testing (QST): refined stratification for age and a novel method for statistical comparison of group data. Pain. 2010 Dec;151(3):598-605. doi: 10.1016/j.pain.2010.07.026. Epub 2010 Oct 20.

  PMID: 20965658 BACKGROUND

• Rolke R, Baron R, Maier C, Tolle TR, Treede -DR, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006 Aug;123(3):231-243. doi: 10.1016/j.pain.2006.01.041. Epub 2006 May 11.

  PMID: 16697110 BACKGROUND

• Kemler MA, Schouten HJ, Gracely RH. Diagnosing sensory abnormalities with either normal values or values from contralateral skin: comparison of two approaches in complex regional pain syndrome I. Anesthesiology. 2000 Sep;93(3):718-27. doi: 10.1097/00000542-200009000-00021.

  PMID: 10969305 BACKGROUND

• Rosenberger DC, Pogatzki-Zahn EM. Chronic post-surgical pain - update on incidence, risk factors and preventive treatment options. BJA Educ. 2022 May;22(5):190-196. doi: 10.1016/j.bjae.2021.11.008. Epub 2022 Feb 24. No abstract available.

  PMID: 35496645 BACKGROUND

MeSH Terms

Conditions

Chronic Pain; Pain, Postoperative

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 25, 2019
• First Posted: May 29, 2019
• Study Start: July 1, 2019
• Primary Completion: June 28, 2022
• Study Completion: September 1, 2023
• Last Updated: February 22, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR

Locations

DK (1)