Activation of A-delta-fibres and C-fibres in a First Degree Thermal Injury in Volunteers

NCT02442726 | Completed

• 1 other identifier: H-2-2014-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to measure reaction times and thermal detection thresholds to CO2 laser stimulation of the skin, before and after a first degree thermal injury, in the primary and secondary hyperalgesia area, in order to investigate whether different nerve-fiber classes are activated in the post-injury phase. The study results are expected to uncover existence of a peripheral inflammatory input contributing to secondary hyperalgesia.

Conditions

Healthy Subjects

Keywords

Heat Injury; Humans; Laser Stimulation; Quantitative Sensory Testing; Reaction Time; Secondary Hyperalgesia; Thermal Thresholds

Outcome Measures

Primary Outcomes (2)

• Changes in distribution of reaction times assessed by laser stimuli in the thermal injury area (the primary hyperalgesia area) comparing post-injury values with pre-injury, baseline values.

  Assessments are performed at Baseline, 1 h post-thermal injury and 24 h post-thermal injury. Changes compared to Baseline are analyzed.

  24 hours

• Changes in distribution of reaction times assessed by laser stimuli in the secondary hyperalgesia area comparing post-injury values with pre-injury, baseline values.

  Assessments are performed at Baseline, 1 h post-thermal injury and 24 h post-thermal injury. Changes compared to Baseline are analyzed.

  24 hours

Secondary Outcomes (4)

• Changes in thermal pain thresholds assessed by laser stimuli in the thermal injury area (the primary hyperalgesia area) comparing post-injury values with pre-injury, baseline values.

  24 hours

• Changes in thermal pain thresholds assessed by laser stimuli in the secondary hyperalgesia area comparing post-injury values with pre-injury, baseline values.

  24 hours

• Thermal detection thresholds assessed by laser stimuli in the thermal injury area (the primary hyperalgesia area) comparing post-injury values with pre-injury, baseline values.

  Baseline, 1 h post-thermal injury; 24 h post-thermal injury

• Changes in thermal detection thresholds assessed by laser stimuli in the secondary hyperalgesia area comparing post-injury values with pre-injury, baseline values.

  24 hours

Study Arms (2)

Thermal Injury

ACTIVE COMPARATOR

A first degree heat injury is induced by a contact thermode (12.5 cm2; 47C; 420 s) applied at the skin at the lower leg. CO2-Laser stimulation (Laser Stimulation Device, SIFEC)

Device: CO2-Laser stimulation (Laser Stimulation Device, SIFEC)

Sham Injury

SHAM COMPARATOR

A sham "injury" is induced by a contact thermode (12.5 cm2; 38C; 420 s) applied at the skin at the lower leg. CO2-Laser stimulation (Laser Stimulation Device, SIFEC) is used to assess

Device: CO2-Laser stimulation (Laser Stimulation Device, SIFEC)

Interventions

CO2-Laser stimulation (Laser Stimulation Device, SIFEC) DEVICE

Laser stimuli are evenly applied in 15 spots (each 6 mm in diameter) in the primary hyperalgesic zone (application zone of the contact thermode) and in the secondary hyperalgesic zone (1 cm outside the application zone of the contact thermode).

Sham Injury; Thermal Injury

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy right-handed males
• non-smokers (due to fluctuating skin temperatures in smokers)
• normal thermal perception (warmth detection threshold \[WDT\], cool detection threshold \[CDT\] and heat pain threshold \[HPT\])
• familiarized with the thermal injury and quantitative sensory testing
• understands written and verbal study information in Danish
• understands written and verbal study information in English

You may not qualify if:

• lesions on the lower leg
• unable to cooperate with the sensory testing
• suspected neurological disease
• hereditary predisposition to peripheral neurological disease
• inability to develop secondary hyperalgesia area (non-responder)14
• "small-area" responder (secondary hyperalgesia area \< 36 cm2)
• participated in pharmacological trials during the preceding 4 weeks
• participated in a thermal-injury trial during the preceding 8 weeks
• intake of any medication during the preceding 48 hours
• intake of prescription drugs during the preceding 7 days

Sponsors & Collaborators

• University of Copenhagen: lead

Study Sites (1)

BRAINLab, Department of Neuroscience and Pharmacology, Panum Institute

Copenhagen, 2200, Denmark

Location

Related Publications (16)

• Pedersen JL, Kehlet H. Hyperalgesia in a human model of acute inflammatory pain: a methodological study. Pain. 1998 Feb;74(2-3):139-51. doi: 10.1016/s0304-3959(97)00160-7.

  PMID: 9520228 BACKGROUND

• Naert ALG, Kehlet H, Kupers R. Characterization of a novel model of tonic heat pain stimulation in healthy volunteers. Pain. 2008 Aug 15;138(1):163-171. doi: 10.1016/j.pain.2007.11.018. Epub 2008 Jan 22.

  PMID: 18207325 BACKGROUND

• Pedersen JL, Kehlet H. Secondary hyperalgesia to heat stimuli after burn injury in man. Pain. 1998 Jun;76(3):377-384. doi: 10.1016/S0304-3959(98)00070-0.

  PMID: 9718256 BACKGROUND

• Torebjork HE, LaMotte RH, Robinson CJ. Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: simultaneous recordings in humans of sensory judgments of pain and evoked responses in nociceptors with C-fibers. J Neurophysiol. 1984 Feb;51(2):325-39. doi: 10.1152/jn.1984.51.2.325.

  PMID: 6707724 BACKGROUND

• Cook AJ, Woolf CJ, Wall PD. Prolonged C-fibre mediated facilitation of the flexion reflex in the rat is not due to changes in afferent terminal or motoneurone excitability. Neurosci Lett. 1986 Sep 25;70(1):91-6. doi: 10.1016/0304-3940(86)90443-x.

  PMID: 3774223 BACKGROUND

• Woolf CJ, Wall PD. Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat. J Neurosci. 1986 May;6(5):1433-42. doi: 10.1523/JNEUROSCI.06-05-01433.1986.

  PMID: 3711988 BACKGROUND

• Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol. 1992 Mar;448:765-80. doi: 10.1113/jphysiol.1992.sp019069.

  PMID: 1593489 BACKGROUND

• LaMotte RH, Lundberg LE, Torebjork HE. Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol. 1992 Mar;448:749-64. doi: 10.1113/jphysiol.1992.sp019068.

  PMID: 1593488 BACKGROUND

• Werner MU, Petersen KL, Rowbotham MC, Dahl JB. Healthy volunteers can be phenotyped using cutaneous sensitization pain models. PLoS One. 2013 May 9;8(5):e62733. doi: 10.1371/journal.pone.0062733. Print 2013.

  PMID: 23671631 BACKGROUND

• Franz M, Spohn D, Ritter A, Rolke R, Miltner WHR, Weiss T. Laser heat stimulation of tiny skin areas adds valuable information to quantitative sensory testing in postherpetic neuralgia. Pain. 2012 Aug;153(8):1687-1694. doi: 10.1016/j.pain.2012.04.029. Epub 2012 May 31.

  PMID: 22657400 BACKGROUND

• Arendt-Nielsen L, Chen AC. Lasers and other thermal stimulators for activation of skin nociceptors in humans. Neurophysiol Clin. 2003 Dec;33(6):259-68. doi: 10.1016/j.neucli.2003.10.005.

  PMID: 14678840 BACKGROUND

• Martinez V, Ammar SB, Judet T, Bouhassira D, Chauvin M, Fletcher D. Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model. Pain. 2012 Jul;153(7):1478-1483. doi: 10.1016/j.pain.2012.04.004. Epub 2012 May 2.

  PMID: 22560289 BACKGROUND

• Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

  PMID: 16698416 BACKGROUND

• Johansen A, Schirmer H, Stubhaug A, Nielsen CS. Persistent post-surgical pain and experimental pain sensitivity in the Tromso study: comorbid pain matters. Pain. 2014 Feb;155(2):341-348. doi: 10.1016/j.pain.2013.10.013. Epub 2013 Oct 18.

  PMID: 24145207 BACKGROUND

• Plaghki L, Mouraux A. How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation. Neurophysiol Clin. 2003 Dec;33(6):269-77. doi: 10.1016/j.neucli.2003.10.003.

  PMID: 14678841 RESULT

• Ravn P, Frederiksen R, Skovsen AP, Christrup LL, Werner MU. Prediction of pain sensitivity in healthy volunteers. J Pain Res. 2012;5:313-26. doi: 10.2147/JPR.S33925. Epub 2012 Aug 29.

  PMID: 23055774 RESULT

MeSH Terms

Conditions

Hyperalgesia

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mads U Werner, MD, DMSc

  Neuroscience Center, Copenhagen University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

• Ron Kupers, MSc

  Panum Institute, Copenhagen University, Denmark

  STUDY CHAIR

• Henrik Kehlet, MD, DMSc

  JMC, Copenhagen University Hospital, Denmark

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, DMSc

Study Record Dates

• First Submitted: May 3, 2015
• First Posted: May 13, 2015
• Study Start: May 1, 2015
• Primary Completion: September 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 3, 2015

Record last verified: 2015-12

Locations

DK (1)