Two Point Discrimination (TPD)

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.

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.

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

Two group, single blind for chronic pain patients receiving intervention, additional basic science component with baseline comparisons between patients and healthy controls.

Participant in the Chronic Pain Group are initially blinded to the intervention they will be receiving in the study. Healthy participants under go all assessments in the study.

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

Ratings of current pain intensity on a non-numerical visual analog scale ranging from "not at all intense" to "most intense pain sensation imaginable" and of pain unpleasantness on a non-numerical visual analog scale ranging from "not at all unpleasant" to "most unpleasant pain imaginable".

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.