Dopamine Signaling as a Non-Opioid Analgesic Strategy for Chronic Pain

Publication Date

July 2019

Location

LSU Health Medical Education Building

Document Type

Abstract

Start Date

26-7-2019 9:00 AM

End Date

26-7-2019 12:00 PM

Description

Prescription opioids are a critical first-line treatment for chronic pain. However, chronic treatment with opioids can lead to paradoxical increases in pain sensitivity, termed hyperalgesia, which may promote use of opioids to manage worsening pain symptoms. Decreases in ventral striatal dopamine have been reported in chronic pain states. In this study, we used a rodent model of chronic inflammatory pain to investigate the therapeutic efficacy of dopamine receptor agonist medication, pramipexole, as a non-opioid analgesic strategy for chronic pain. Adult male Long-Evans rats received Complete Freund’s Adjuvant (CFA) or saline injections into the left hindpaw. CFA animals demonstrated a persistent decrease in paw withdrawal thresholds in the left paw, indicating mechanical hyperalgesia. Animals received injections of pramipexole (1mg/kg, s.c.) or vehicle (saline) 1 hour prior to measuring von Frey thresholds. Our findings indicate that systemic administration of pramipexole attenuated pain in animals with chronic inflammatory pain by increasing paw withdrawal thresholds following acute and repeated pramipexole treatment. Currently, we are investigating the neurobiological mechanisms underlying the anti-hyperalgesic efficacy of pramipexole using Western blotting. We expect that this efficacy will be based on the drug’s ability to normalize dopamine signaling and reduce neuroinflammation and ROS in the ventral striatum.

Comments

Mentor: Scott Edwards, PhD, LSU Health Sciences Center, Alcohol & Drug Abuse Center of Excellence, Neuroscience Center of Excellence

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Jul 26th, 9:00 AM Jul 26th, 12:00 PM

Dopamine Signaling as a Non-Opioid Analgesic Strategy for Chronic Pain

LSU Health Medical Education Building

Prescription opioids are a critical first-line treatment for chronic pain. However, chronic treatment with opioids can lead to paradoxical increases in pain sensitivity, termed hyperalgesia, which may promote use of opioids to manage worsening pain symptoms. Decreases in ventral striatal dopamine have been reported in chronic pain states. In this study, we used a rodent model of chronic inflammatory pain to investigate the therapeutic efficacy of dopamine receptor agonist medication, pramipexole, as a non-opioid analgesic strategy for chronic pain. Adult male Long-Evans rats received Complete Freund’s Adjuvant (CFA) or saline injections into the left hindpaw. CFA animals demonstrated a persistent decrease in paw withdrawal thresholds in the left paw, indicating mechanical hyperalgesia. Animals received injections of pramipexole (1mg/kg, s.c.) or vehicle (saline) 1 hour prior to measuring von Frey thresholds. Our findings indicate that systemic administration of pramipexole attenuated pain in animals with chronic inflammatory pain by increasing paw withdrawal thresholds following acute and repeated pramipexole treatment. Currently, we are investigating the neurobiological mechanisms underlying the anti-hyperalgesic efficacy of pramipexole using Western blotting. We expect that this efficacy will be based on the drug’s ability to normalize dopamine signaling and reduce neuroinflammation and ROS in the ventral striatum.