# Dissecting Central Mechanisms of Hypoalgesia in Schizophrenia

> **NIH NIH R21** · BOSTON CHILDREN'S HOSPITAL · 2020 · $490,088

## Abstract

ABSTRACT
In individuals diagnosed with schizophrenia (SZ), there is a reduced sensitivity towards endogenous or
exogenous pain stimuli. This hypoalgesic phenotype is considered to be a major cause as to why patients fail
to seek clinical treatment for conditions such as cardiovascular (CVD) or metabolic diseases, where pain is
often a presenting symptom. An unfortunate, yet likely preventable outcome of poorly treated physical
conditions is premature mortality in the SZ patient population. In fact, delayed treatment or an absence of
clinical care all together of CVDs in SZ has been reported to cause 12 and 15 years of reduced lifespans in
female and male patients, respectively.
 Currently, the clinical characteristics across the SZ spectrum or the aberrant neurobiological
mechanisms linked with reduced pain perception in SZ patients are in large part unknown. Clinical feature of
SZ such as positive and negative symptoms may be involved in reducing the overall salience of pain and as a
result, produce what is in the end observed as a hypoalgesic effect. Moreover, domains such as reward-
aversion, cognitive, autonomic or sensorimotor processing are important to consider in the context of
hypoalgesia in SZ as these are dysregulated in this population as well as are intertwined with salience and
pain perception.
 In the current proposal, we outline a thorough approach to identify how positive and negative clinical
symptoms measured in SZ patients relate to hypoalgesia. Moreover, we define a strategy that aims to
determine the central, neurobiological constructs that are functionally and structurally altered in SZ and that
underpin a hypoalgesic state. We propose to cross-sectionally evaluate 30 SZ patients and matched, healthy
subjects (N=30) using a combination of evoke heat pain, blood-oxygenated level dependent functional
magnetic resonance imaging in conjunction with clinical (Scale for the Assessment of Negative Symptoms),
behavioral (quantitative sensory testing, effort expenditure for rewards task, and emotion mapping) and
physiological (skin conductance and heart rate) measures. Our central hypothesis is that the severity of
negative symptoms, particularly anhedonia and reduced self-awareness, will coincide with hypoalgesic
responses to experimentally evoked pain. We further hypothesize that a down-regulation of brain systems
mediating pain salience (e.g., autonomic, mesolimbic and nigrostriatal) drive altered pain perception in SZ. Our
Specific Aims are: Aim 1: Identify clinical, cognitive, physiological and behavioral predictors of hypoalgesic
response to noxious heat stimuli in SZ. Aim 2: Characterize central, evoked pain responses in SZ. Aim 3:
Using resting-state fMRI, identify circuit abnormalities that are associated with hypoalgesia in SZ. To carry out
this work, we have formed a team of clinical researchers with robust experience in investigation of pain
mechanism, treatment and investigation of SZ patients and utilization of neuroim...

## Key facts

- **NIH application ID:** 9958036
- **Project number:** 1R21MH122967-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ANN Kyungah SHINN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $490,088
- **Award type:** 1
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958036

## Citation

> US National Institutes of Health, RePORTER application 9958036, Dissecting Central Mechanisms of Hypoalgesia in Schizophrenia (1R21MH122967-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9958036. Licensed CC0.

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