# Human Networks for Behaviors related to the Expectation of Pain

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $614,501

## Abstract

The conditioned expectation or fear of pain often results in disability produced by stimuli related to a painful
injury on the job, although the neuroscience of this expectation is unclear. Conditioned expectation in humans
can be produced by a protocol that consists of a train of visual conditioning stimuli, some of which are paired
(CS+) with a painful laser pulse unconditioned stimulus (US). We now propose to use this protocol to study two
domains of this expectation: the experience of pain produced by the laser when it follows the CS+, and the
anticipation of pain produced by the CS+. The latter is related to avoidance of future pain and the former is
related to escape from current pain instead of approach, e.g. noncompliance with physical therapy which can
cause some pain. Increases in either avoidance or escape behaviors are related to occurrence of, and worse
outcomes in, chronic pain syndromes from osteoarthritis to fibromyalgia.
 We propose to study the two domains by recording local field potentials (LFP) directly from anatomic
components in the brain involved in these two domains for the expectation of pain. Our Preliminary Data shows
LFP activations (ERPs Event Related Potentials & ERS/ERD - increases/ decreases in oscillatory power) in the
Amygdala (AMY), Hippocampal formation and parts of the cingulate cortex in response to the unpaired CS+ and
US, which may mediate conditioning and produce Conditioned Responses (CRs). CRs for anticipation include
increases in: autonomic activity (Skin Conductance Response, SCR), and in ratings of the association between
the CS+ and US, and CS unpleasantness and attention produced by a stimulus (salience). The experience of the
US was painful, unlike the CS, and was related to conditioning but not to CS unpleasantness or salience, which is
consistent with the presence of two separate domains. The CS SCR was related to ERS/ERD and ERC as a
function of both frequency bands and components which were different from those related to the CS+ US
association which, in turn, were different from those related to CS unpleasantness and CS salience. Model
networks for each domain are suggested by these Data, and are supported by the evidence of studies of
anatomic projections and fMRI signals. These two models share components including nuclei within the AMY,
Anterior and Mid-Cingulate, but differ in components of the Hippocampal formation, Insula, and Lateral Prefrontal
Cortex, and in Local networks defined by the presence of of components within one structure or within adjacent
structures. Our premise is that components in these models will be involved in pain and conditioning processes,
and show activations related to one of the two domains as individual components or as part of Local Network, and
will show interactions that define a distributed, Hierarchical network for that domain.
 This study may suggest sites of interest in drug development and in surgical or stimulation therapies for
pain syndromes with ...

## Key facts

- **NIH application ID:** 10072086
- **Project number:** 5R01NS109298-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Fred Lenz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $614,501
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072086

## Citation

> US National Institutes of Health, RePORTER application 10072086, Human Networks for Behaviors related to the Expectation of Pain (5R01NS109298-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10072086. Licensed CC0.

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