# Impact of Chronic Pain on Circuitry Involved in Opioid Self-Administration Behaviors

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $237,218

## Abstract

ABSTRACT
Opioid abuse in the USA has recently reached epidemic proportions, with 29,440 of the 47,055 fatalities from
drug poisoning in 2014 attributable to either therapeutic opioids or heroin. Prescription opioids such as
morphine, oxycodone and fentanyl as well as heroin are widely abused. The recent increase in opioid abuse is
mirrored by a skyrocketing 500-1000% increase in the number of pain prescriptions over the last decade,
although the abuse of therapeutic opioids is largely a result of diversion. In spite of the alarming statistics it must
be acknowledged that pain requires and demands treatment. The role of pain in opioid addiction is murky; with
some studies claiming addiction liability is enhanced by pain, yet others claiming that pain is protective.
Technically challenging self-administration of morphine, oxycodone and remifentanil in mice (that were
developed during the past funding period) will be used to assess the influence of neuropathic pain on phases of
the establishment of opioid self-administration followed by cycles of withdrawal (extinction) and relapse (re-
exposure). Our preliminary data suggest that neuropathic pain does not alter initial oxycodone self-
administration but enhances drug-seeking during extinction and causes an enhanced escalation in drug taking
during re-exposure. These findings will be expounded upon in Aims 1a and 1b using different opioid drugs and
doses in self-administration protocols. The duration of time after sciatic nerve injury will be a variable since we
have recently shown that pain symptoms can dissipate over time due to an increase in constitutive signaling of
mu opioid receptors (MOR), yet negative affect continues to incubate over time. Given negative affect
accompanies both chronic pain and opioid withdrawal, we will test in Aim1c if inhibiting neuroinflammation
(published during the past funding period to be induced both by chronic opioid treatment and chronic pain), or
kappa opioid receptors, (that we show in preliminary data have markedly increased function during chronic pain)
will modify oxycodone reinforcement behaviors in animals with or without neuropathic pain. To identify MOR cell
types and the striatal and/or habenula circuitry that are required for aspects of the opioid reward profile, Aim 2
will use conditional deletion or knock-in strategies to remove or insert MOR in striatal and extra-striatal neurons.
Preliminary data shows marked differences in the self-administration profiles of these mice. For example,
removing MOR from D1 neurons increases oxycodone consumption and drug seeking during extinction despite
a complete absence of oxycodone-induced locomotor sensitization, while the converse is seen in mice lacking
MORs on D2 neurons. Electrophysiological analyses will determine if pain alters properties of different striatal
neurons following opioid self-administration. Finally, as D2 cells contribute to negative affect during withdrawal,
we will use optogenetic stimula...

## Key facts

- **NIH application ID:** 9964748
- **Project number:** 5P50DA005010-34
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** CHRISTOPHER J. EVANS
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,218
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964748

## Citation

> US National Institutes of Health, RePORTER application 9964748, Impact of Chronic Pain on Circuitry Involved in Opioid Self-Administration Behaviors (5P50DA005010-34). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9964748. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*