(826.14) Sex differences in behavior and immune response revealed by a NSAID nanotherapeutic treatment during peripheral neuroinflammation

Poster Board Number: D32

Brooke Deal (Duquesne University), Laura Reynolds (Thomas Jefferson Universituy, Thomas Jefferson Universituy), Jelena Janjic (Duquesne University), John Pollock (Duquesne University)

Until recently, the majority of preclinical neuroinflammatory studies were performed on males. Because of this, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. A major focus has been on the macrophage and its contribution to the development of neuropathic pain. Under a typical response, the macrophage upregulates expression of cyclooxygenase-2 (COX-2), which in turn leads to the production of proinflammatory prostaglandin E2 (PGE2), which is linked to neuronal sensitization and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to attenuate PGE2 by the inhibition of COX-2. However, a problem with NSAIDs is that due to the systemic dosage needed to achieve neuropathic pain relief there are risks of off-target toxicity. This study evaluated a COX-2 inhibiting nanotherapeutic in its ability to relieve neuropathic inflammation and pain-like behavior of a chronic constriction injury (CCI) of the right sciatic nerve. We find that under the same injury, both males and females exhibit the same degree of hypersensitivity represented as pain-like behavior. We also find that the nanotherapeutic was able to relieve pain-like behavior in both sexes, but females experienced less relief. This behavioral response was reflected in the number of infiltrating macrophages at the site of injury; where again, both sexes had decreased inflammation but the females had significantly more macrophages present than the males.

JMJ acknowledges NIH NIDA 1R21DA039621amp;ndash;01. JAP acknowledges the NSF DBI 1726368 and C.H. Leach II Fund. J.M.J. amp;amp; J.A.P. acknowledges support from CDMRP award W81XWH-20-1-0854 and DOD award W81XWH-19-DMRDP-CRMRP-RESTORE.