Temporospatial expression of reactive nitroxidative species in supraspinal regions during the induction and maintenance of central sensitization

Abstract

Reactive nitroxidative species are implicated in the development and maintenance of central sensitization in pain states. The purpose of this pilot study was to describe the temporospatial and cellular expressions of the neuronal nitric oxide synthase (nNOS) isoform in supraspinal regions during pain states and therefore determine if these sites are acceptable for future investigations of related nitroxidative species. An inflammatory pain model was used to evaluate changes in nNOS expression in the rostral ventromedial medulla (RVM) and periaqueductal gray (PAG), sites that modulate nociception. Eight (n=8) Sprague Dawley rats received subcutaneous hindpaw injections of either carrageenan or saline and were evaluated for hyperalgesia and immunofluorescence. Our findings revealed a bilateral increase in nNOS positive neurons before the onset of thermal hyperalgesia (3 hours post carrageenan, n=2) compared to the saline group in the RVM (Fold change: Ipsilateral: 3; Contralateral: 3.5) and dorsolateral PAG (Fold change: Ipsilateral: 1.7; Contralateral: 1.7). These changes persisted during hyperalgesia (6 hours post carrageenan, n=2). Our preliminary results lead us to hypothesize that formation of nitroxidative species at supraspinal sites, specifically the RVM and PAG, may contribute to central sensitization. Support: Saint Louis University Center for Anatomical Science and Education.