The long-term goal of this proposal is to identify non-opioid drugs that harness endogenous
anti-inflammatory mechanisms resulting in the suppression of proinflammatory cytokines such
as IL-1ß providing a novel approach to treat chronic pain in people while lacking potential
for addictive side effects.
Specific Aim I: pramipexole blocks the activation of NLRP3 and consequent production and
release of the proinflammatory cytokines IL-1ß, IL-6 and TNF-α, and increases production of
the anti-inflammatory cytokine interleukin-10 (IL-10).
The goal of Aim I (Phase I) experiments is to examine the specific anti-inflammatory
mechanisms of pramipexole on PAMP, DAMP and opioid stimulated immune cells, THP-1 cells will
be used.
Specific Aim II: pramipexole treatment will provide therapeutic benefit to patients
experiencing suboptimal pain relief from current standard therapy with concurrent reduction
of TLR4-NLRP3-cytokine expression in peripheral blood mononuclear cells.
The goal of Aim II (Phase II) will be to determine the therapeutic benefit of pramipexole for
pain, which is a repurposing of this FDA-approved drug with a good safety profile.
1.2. Our overarching hypothesis is that pramipexole will control clinical pain by suppressing
the activation of the TLR4-NLRP3-IL-1ß pathway and prevent IL-1ß release from peripheral
immune cells. These findings have provided the current impetus to examine pain therapeutic
drugs targeting immune-related factors either upstream or downstream of IL-1ß signaling.
Phase:
Early Phase 1
Details
Lead Sponsor:
University of New Mexico
Collaborator:
University of New Mexico Clinical and Translational Science Center