Neurobiology of pain and behavior changes associated with rare diseases and developmental disabilities

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Abstract

Intellectual disability is characterized by significant deficits in intellectual functioning (reasoning, problem solving, planning, abstract thinking, judgement) and adaptive functioning, including conceptual, social and practical skills, which occur during the developmental period. Deficits can range from mild to profound and are reflected in distinct levels of motor, cognitive and communication impairment. Individuals with intellectual disability (ID) present with high levels of co-occurring physical disabilities and medical conditions that makes them especially vulnerable to experiencing pain. Many patients with ID have skeletal abnormalities that are associated with pain including scoliosis, osteopenia, pathological fractures, hip subluxation, pathological fractures. Additionally, individuals with ID have a high prevalence of neuromotor disorders including decreased mobility, immobility, spasticity, sustained muscle contractions, dyskinesia. All these co-morbidities can be associated with an increased incidence of pain. These patients often require surgery to treat these co-morbidities, which in turn is associated with post-operative pain. Further, while chronic pain is a prevalent problem and an additional source of difficulty in individuals with ID who already experience disadvantage, research on pain in this population is sorely lacking and the existing evidence that individuals with ID might have altered nociception, pain processing, and pain response is inconclusive. A number of reasons contribute to this paucity of information including the long-standing belief that individuals with ID are insensitive or indifferent to pain, the lack of methods to measure pain in individuals who are unable to verbally communicate and self-report pain, and researchers' hesitation to include vulnerable groups in pain research. We aim to determine whether individuals with severe ID have alterations on somatosensory response to noxious stimuli. We will also conduct mechanistic studies in well characterized mouse models that harbor gene mutations known to be associated with increased risk for autism spectrum disorder and intellectual disabilities. In this previous cycle we assembled a group of collaborators with the collective expertise needed to characterize the cortical temporal and spatial relationship of neural (using electroencephalography, EEG) and hemodynamic (using functional near red spectroscopy, fNIRS) responses to innocuous and noxious stimuli both in healthy controls and in ID subjects. We aim to determine whether individuals who appear to have abnormal nociceptive responsivity (ID sample) have different neural and hemodynamic response to innocuous and noxious stimuli compared with typically developing subjects. We will also include physiological (heart rate, galvanic skin response and pupil dilation) as well as behavioral indices of nociception/ pain (e.g. vocal, social, facial, activity, body and limbs), as they can provide complementary information about nociception in this population