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Neuroscience Brown Bag Series

Thursday, November 01, 2018,

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  • Location: Wilson Hall • 111 21St Ave S • Nashville, TN 37240
  • Room: 316

Ronald Wiley, MD, PhD

Professor of Neurology

Vanderbilt University Medical Center

"The Role of Substance P Receptor-Expressing Dorsal Horn Neurons in Pain"

Although opiate analgesics are widely abused, they remain unsurpassed in treating moderate to severe acute pain.  However, opiates and other available analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) are highly problematic when used to treat chronic pain, a major clinical challenge in older adults.  The search for better, non-opiate/non-NSAID approaches to chronic pain motivated the work to be discussed.  Several lines of evidence have long implicated the neuropeptide, substance P (SP), in pain neurobiology, but understanding of the specific role of SP-secreting neurons and/or neurons expressing SP receptors (NK-1R) in nociception was incomplete.  The evidence implicating SP neurons and NK-1R expressing neurons will be presented followed by our work using a targeted toxin, SP-saporin, to selectively destroy NK-1R expressing neurons in the superficial layers of the dorsal horn.  Somewhat surprisingly, animals treated with this toxin showed intact nocifensive reflex responses to painful stimuli (i.e. paw withdrawal), but significant reduction in operant responses to thermal pain stimuli and virtually complete absence of hyperalgesia and allodynia, two important aspects of chronic pain.  The dorsal horn physiology underlying the behavioral observations will be discussed along with some unanswered questions regarding dorsal horn pain processing.  The potential therapeutic usefulness of SP-saporin will also be considered as well as some related agents and some lessons learned from this line of investigation.