Prenatal alcohol exposure (PAE) results in deficiencies of the central nervous system (CNS) and an overactive proinflammatory neuroimmune response. This response is mediated by cytokines secreted from infiltrating peripheral immune cells like T cells that secrete interferon-g (IFNg). Interleukin-10 is a potent anti-inflammatory cytokine that inhibits the production of a variety of proinflammatory cytokines. While IFN is secreted from and further activates T cells, it is also secreted from activated macrophage in response to tissue injury and inflammation and further enhances inflammatory processes. Neuropathic pain results from damage to peripheral nerves and can be experienced as an increased sensitivity to light touch, known as allodynia. Prenatal alcohol exposure is a risk factor for developing allodynia via enhanced neuroimmune, proinflammatory actions in the CNS such as the spinal cord. For this study, dexpramipexole [(+)-pramipexole, the enantiomer of the drug (-)-pramipexole)] exerts little activity at the dopamine D2/D3 receptor, but reduces caspase-3 activation suggesting that it may suppress inflammatory processes via anti- inflammatory actions. Work from our lab reveals intrathecal (i.t.; subarachnoid, surrounding the spinal cord) dexpramipexole reverses chronic allodynia in PAE male rats (see J.R. Zimmerly; this poster session). Here, we administered i.t. dexpramipexole to female non-PAE and PAE rat offspring with/without nerve damage to test whether direct exposure to spinal glia and spinal immune cells reverses allodynia. Allodynia was assessed using the von Frey fiber test before and after i.t. dexpramipexole. Cells collected from the spleen were analyzed for IL-10 and IFNγ mRNA levels following lipopolysaccharide (LPS) stimulation with or without dexpramipexole. Results revealed non-PAE and PAE female rat offspring were non-responsive to i.t. dexpramipexole. Splenocytes from PAE rats demonstrated a blunted IL-10 and IFNγ mRNA response to LPS and dexpramipexole compared to non-PAE controls, suggesting anti-inflammatory actions in PAE females are suppressed.
Pasmay, Andrea A.; Justine R. Zimmerly; Shahani Noor; Annette K. Fernandez; Melody S. Sun; Suzy Davies; Daniel D. Savage; C Fernando Valenzuela; Nikolaos Mellios; Rodrigo Escalona; and Erin D. Milligan. "Effect of dexpramipexole in Neuropathic pain in prenatal alcohol exposed female subjects." (2021). https://digitalrepository.unm.edu/hsc-bbhrd/29