Two Point Discrimination

NCT ID: NCT03686748

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-21
• Study Completion Date: 2027-07-16

Brief Summary

SPECIFIC AIMS

Pain in both youth and adults is a complex, subjective and personal experience, and remains poorly understood. One particularly perplexing dimension of some forms of pain is the tendency of pain to spread outside of an affected body site to adjacent location, and then to unaffected body sites. Such widespread pain may reflect an altered spatial tuning of somatosensory processing, such that lateral inhibition is diminished, thereby allowing pain to spread. To date, no therapies exist which are designed specifically to diminish or even reverse the spatial spread of pain. However, training in two-point discrimination holds the potential to retune spatial aspects of somatosensory processing and may represent a novel therapy for widespread pain. Thus, the present investigation will test the following aims:

Aim 1. Do youth with chronic pain have disrupted spatial tuning of somatosensory processing? Deficits in two point tactile discrimination have long been noted in adults with chronic pain, but such deficits remain poorly documented in pediatric chronic pain patients. In order to determine if such deficits exist, youth with both chronic pain and healthy youth will undergo assessment of two point discrimination thresholds.

Aim 2. Does two-point discrimination training result in diminished pain and disability in youth with somatic pain? After initial characterization of tactile discrimination thresholds, youth with chronic pain will participate in multiple sessions of either two-point discrimination training or a single-point spatially-directed attentional control condition. Training will involve up to 9 additional sessions. Efficacy of training will be assessed by 1) reductions in the spatial extent of pain, 2) reductions in pain intensity and unpleasantness, and 3) reductions in pain-related disability.

Detailed Description

STUDY DESIGN Prior to commencing this investigation, investigators will optimize the tactile discrimination threshold testing (i.e. as per baseline visit, below), and the training conditions, in up to ten participants (patients and/or healthy controls). This will serve as a pilot to refine operational aspects of study procedures before investigators commence the main investigation proposed herein. Following this, youth with either chronic pain (ages 10-17, n=40) or healthy youth (ages 10-17, n=20) will undergo assessments of two-point and single-point discrimination thresholds in an initial session (Aim 1). After this initial session, youth with chronic pain will participate in up to 9 additional sessions of attentional training (Aim 2). These chronic pain patients will be randomized to either two-point discrimination training (n=20) or a single-point spatially-directed attentional control condition (n=20). Participants will not be informed of which intervention they will receive (single-blind study). Psychological questionnaires will be completed in the first and last sessions in order to determine how these variables relate to tactile discrimination and response to training.

STUDY INTERVENTIONS 5.1 Two Point Discrimination Training: Two-point discrimination threshold (TPD) training may be performed 1) at spatial locations remote from pain, 2) at spatial locations adjacent to the region of pain, and/or 3) at spatial locations in the site of pain, if the participant will tolerate it. TPD is defined as the smallest distance between two points at which someone can recognize two points, and not one, touching their skin. As such this is a test of one's ability to identify separate stimulation of two discrete areas, and relies heavily on lateral inhibition. Highly precise mechanical calipers will be gently placed onto the skin and the distance between the prongs will be increased/decreased. After repeated decreases and increases in the distance between the prongs, the TPD will be deemed as the distance at which participants consistently report two points instead of one. One-point stimuli will be interleaved to serve as a control condition. Participants will be informed immediately of correct and incorrect responses as part of the discrimination training.

5.2 Control Stimulation: Participants will undergo a single-point discrimination training at the same sites as described above. Probes of different sizes will be used for this portion - a small diameter probe (~1-5 mm) and a large diameter probe (~6-50mm). The probes will be gently placed in contact with the participants' skin, and the participant will be instructed to respond if they were contacted with the small or large probe. Participants will be informed immediately of correct and incorrect responses as part of the discrimination training.

Conditions

Ehlers-Danlos Syndrome (EDS); Complex Regional Pain Syndrome (CRPS); Amplified Musculoskeletal Pain Syndrome (AMPS); Low Back Pain; Fibromyalgia; Chronic Widespread Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Two-point intervention

Two point discrimination training.

Group Type: EXPERIMENTAL

Two-point discrimination training

Intervention Type: BEHAVIORAL

Patients will undergo multiple sessions of two-point discrimination training.

One-point intervention

One point discrimination of size of probe

Group Type: ACTIVE_COMPARATOR

One-point discrimination training

Intervention Type: BEHAVIORAL

Patients will undergo multiple sessions of one-point discrimination training.

Healthy Controls

Observational component of differences in discrimination between chronic pain patients and healthy controls.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Two-point discrimination training

Patients will undergo multiple sessions of two-point discrimination training.

Intervention Type: BEHAVIORAL

One-point discrimination training

Patients will undergo multiple sessions of one-point discrimination training.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

Chronic Pain Patients:

• Somatically located chronic pain
• amplified musculoskeletal pain syndrome
• complex regional pain syndrome
• low back pain
• fibromyalgia
• other forms of chronic, widespread pain
• Male or female, 10-17 years
• High fluency in written and oral English language

Control Participants:

• Youth in good general health
• Male or female, 10-17 years
• High fluency in written and oral English language

Exclusion Criteria

• Present significant mental health disorder as defined by DSM V (e.g. psychosis, bipolar disorder, major depression),
• alcohol or drug dependence
• documented developmental delays or impairments (e.g., autism, cerebral palsy, or mental retardation) of a magnitude that would interfere with adherence to study requirements or safe participation in the study
• Primary complaint of migraine or visceral (abdominal) pain, with minimal somatic involvement.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Robert Coghill

Director of Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert C Coghill, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

References

Flor H, Nikolajsen L, Staehelin Jensen T. Phantom limb pain: a case of maladaptive CNS plasticity? Nat Rev Neurosci. 2006 Nov;7(11):873-81. doi: 10.1038/nrn1991.

Reference Type: BACKGROUND

PMID: 17053811 (View on PubMed)

Defrin R, Pope G, Davis KD. Interactions between spatial summation, 2-point discrimination and habituation of heat pain. Eur J Pain. 2008 Oct;12(7):900-9. doi: 10.1016/j.ejpain.2007.12.015. Epub 2008 Feb 14.

Reference Type: BACKGROUND

PMID: 18280188 (View on PubMed)

Flor H, Denke C, Schaefer M, Grusser S. Effect of sensory discrimination training on cortical reorganisation and phantom limb pain. Lancet. 2001 Jun 2;357(9270):1763-4. doi: 10.1016/S0140-6736(00)04890-X.

Reference Type: BACKGROUND

PMID: 11403816 (View on PubMed)

Gardner EP, Martin JH, Jessell TM, Kandel ER, Schwartz JH (2000) Principles of neural science. New York: McGraw-Hill.

Reference Type: BACKGROUND

Groenewald CB, Essner BS, Wright D, Fesinmeyer MD, Palermo TM. The economic costs of chronic pain among a cohort of treatment-seeking adolescents in the United States. J Pain. 2014 Sep;15(9):925-33. doi: 10.1016/j.jpain.2014.06.002. Epub 2014 Jun 19.

Reference Type: BACKGROUND

PMID: 24953887 (View on PubMed)

Hechler T, Wager J, Zernikow B. Chronic pain treatment in children and adolescents: less is good, more is sometimes better. BMC Pediatr. 2014 Oct 13;14:262. doi: 10.1186/1471-2431-14-262.

Reference Type: BACKGROUND

PMID: 25308551 (View on PubMed)

Hestbaek L, Leboeuf-Yde C, Kyvik KO, Manniche C. The course of low back pain from adolescence to adulthood: eight-year follow-up of 9600 twins. Spine (Phila Pa 1976). 2006 Feb 15;31(4):468-72. doi: 10.1097/01.brs.0000199958.04073.d9.

Reference Type: BACKGROUND

PMID: 16481960 (View on PubMed)

Huguet A, Miro J. The severity of chronic pediatric pain: an epidemiological study. J Pain. 2008 Mar;9(3):226-36. doi: 10.1016/j.jpain.2007.10.015. Epub 2007 Dec 21.

Reference Type: BACKGROUND

PMID: 18088558 (View on PubMed)

King S, Chambers CT, Huguet A, MacNevin RC, McGrath PJ, Parker L, MacDonald AJ. The epidemiology of chronic pain in children and adolescents revisited: a systematic review. Pain. 2011 Dec;152(12):2729-2738. doi: 10.1016/j.pain.2011.07.016.

Reference Type: BACKGROUND

PMID: 22078064 (View on PubMed)

Lotze M, Moseley GL. Role of distorted body image in pain. Curr Rheumatol Rep. 2007 Dec;9(6):488-96. doi: 10.1007/s11926-007-0079-x.

Reference Type: BACKGROUND

PMID: 18177603 (View on PubMed)

Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Patterns of cortical reorganization in complex regional pain syndrome. Neurology. 2003 Dec 23;61(12):1707-15. doi: 10.1212/01.wnl.0000098939.02752.8e.

Reference Type: BACKGROUND

PMID: 14694034 (View on PubMed)

Maihofner C, Handwerker HO, Neundorfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome. Neurology. 2004 Aug 24;63(4):693-701. doi: 10.1212/01.wnl.0000134661.46658.b0.

Reference Type: BACKGROUND

PMID: 15326245 (View on PubMed)

Moseley LG, Zalucki NM, Wiech K. Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain. Pain. 2008 Jul 31;137(3):600-608. doi: 10.1016/j.pain.2007.10.021. Epub 2007 Dec 3.

Reference Type: BACKGROUND

PMID: 18054437 (View on PubMed)

O'Sullivan PB, Beales DJ, Smith AJ, Straker LM. Low back pain in 17 year olds has substantial impact and represents an important public health disorder: a cross-sectional study. BMC Public Health. 2012 Feb 5;12:100. doi: 10.1186/1471-2458-12-100.

Reference Type: BACKGROUND

PMID: 22304903 (View on PubMed)

Price DD (1999) Psychological mechanisms of pain and analgesia, 0 Edition. Seattle: IASP Press.

Reference Type: BACKGROUND

Price DD, McHaffie JG, Larson MA. Spatial summation of heat-induced pain: influence of stimulus area and spatial separation of stimuli on perceived pain sensation intensity and unpleasantness. J Neurophysiol. 1989 Dec;62(6):1270-9. doi: 10.1152/jn.1989.62.6.1270.

Reference Type: BACKGROUND

PMID: 2600624 (View on PubMed)

Price DD, Bush FM, Long S, Harkins SW. A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain. 1994 Feb;56(2):217-226. doi: 10.1016/0304-3959(94)90097-3.

Reference Type: BACKGROUND

PMID: 8008411 (View on PubMed)

Quevedo AS, Coghill RC. Attentional modulation of spatial integration of pain: evidence for dynamic spatial tuning. J Neurosci. 2007 Oct 24;27(43):11635-40. doi: 10.1523/JNEUROSCI.3356-07.2007.

Reference Type: BACKGROUND

PMID: 17959806 (View on PubMed)

Quevedo AS, Morch CD, Andersen OK, Coghill RC. Lateral inhibition during nociceptive processing. Pain. 2017 Jun;158(6):1046-1052. doi: 10.1097/j.pain.0000000000000876.

Reference Type: BACKGROUND

PMID: 28195854 (View on PubMed)

Wand BM, Di Pietro F, George P, O'Connell NE. Tactile thresholds are preserved yet complex sensory function is impaired over the lumbar spine of chronic non-specific low back pain patients: a preliminary investigation. Physiotherapy. 2010 Dec;96(4):317-23. doi: 10.1016/j.physio.2010.02.005.

Reference Type: BACKGROUND

PMID: 21056167 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form: Healthy Control

View Document

Document Type: Informed Consent Form: Patient Population

View Document

Other Identifiers

CIN_TPD_001

Identifier Type: -

Identifier Source: org_study_id