Prenatal alcohol exposure (PAE) results in chronic central nervous system (CNS) deficits and heightened neuroimmune responses that persist into adulthood. Young adult animals with moderate PAE display pathological sensitivity to light touch, referred to as allodynia, following sciatic nerve chronic constriction injury (CCI). Allodynia coincides with activated spinal glia and an increased presence of peripheral immune cells that invade the CNS. Activated glia and immune cells release the potent pro-inflammatory cytokine, interleukin-1 (IL-1β). Previous studies have shown that dexpramipexole, an enantiomer of pramipexole, reduces caspase-3 and cell death, suggesting a possible anti-inflammatory action. The current study explored whether dexpramipexole is able to alleviate allodynia via direct intrathecal (i.t.; peri-spinal) application, and whether dexpramipexole can decrease IL-1β protein levels from peripheral immune cells. Long-Evans, 4-mo. male rats exposed prenatally to either saccharin (Sac) as a control or moderate alcohol (PAE) underwent Sham or mild CCI surgery. Hindpaw withdrawal responses to light touch was determined using the von Frey fiber test before and after i.t. dexpramipexole. Separately, splenocytes and cells from the peritoneal cavity (PEC) were collected from Long-Evans male rats, stimulated for 24-hrs with lipopolysaccharide (LPS), or LPS in combination with dexpramipexole followed by IL-1β protein analysis via ELISA assay. The results showed CCI produced clear ipsilateral allodynia in both Sac and PAE rats that was reversed following i.t. dexpramipexole, with maximal effects observed at 60-90 min. While both splenocytes and PEC cells showed increased IL-1β levels after stimulation with LPS, only PEC cells showed reduced IL-1β levels after treatment with dexpramipexole. We demonstrate i.t. dexpramipexole can alleviate allodynia independent of PAE, and that its actions occur at the level of the spinal cord. Furthermore, this is the first demonstration that dexpramipexole acts as a potent anti- inflammatory factor, effectively reducing IL-1β levels from immune-stimulated PEC cells from PAE offspring.
Zimmerly, Justine; Andrea Pasmay; Shahani Noor; Annette Fernandez; Melody Sun; Suzy Davies; Daniel Savage; Nikolaos Mellios; and Erin Milligan. "Effect of dexpramipexole on neuropathic pain in prenatal alcohol exposed male and female subjects." (2021). https://digitalrepository.unm.edu/hsc-bbhrd/24