Prospects for the Personalized Multimodal Therapy Approach to Pain Management via Action on NO and NOS

Abstract

Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.

Peripheral Purinergic Modulation in Pediatric Orofacial Inflammatory Pain Affects Brainstem Nitroxidergic System: A Translational Research

“…In literature, there are poor knowledge about the relationship between orofacial nociception and NO [35,40]. Nevertheless, it has been demonstrated that nNOS [17] and iNOS [41,42] might play a critical role in central mechanisms of the development and/or maintenance of inflammatory pain, supporting our results. Other studies demonstrated the nNOS expression at trigeminal level not only in mammals [43][44][45][46] but also in birds and in reptiles [47].…”

RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation

“…In contrast, the amounts of GPCR Prkar1b ( Marbach et al, 2021 ), P2ry12 ( Defaye et al, 2021 ), and Htr2c ( Brasch-Andersen et al, 2011 ) in the TG were dramatically decreased after CFA injection. For the ion channels, we observed that the noticeably elevated expression of Rapgef3 ( Liu et al, 2021 ), Nos1 ( Shnayder et al, 2021 ), TRPM8 ( Weyer and Lehto, 2017 ), and CXCL12 ( Luo et al, 2016 ) in the TG were remarkably increased after CFA injection. On the contrary, the levels of ion channel transcripts for Sgk3 ( Liu et al, 2015 ) was significantly reduced in the TG after CFA injection.…”

Preface to Nitric Oxide Modulators in Health and Disease I

“…As reviewed by Shnayder N.A. et al, in patients with peripheral chronical pain syndromes, an association can be found between single-nucleotide variants of NOS1 , NOS2 , and NOS3 genes encoding nNOS, iNOS, and eNOS and acute and chronic peripheral pain [ 12 ]. Therefore, the administration of the appropriate NOS inhibitor could be considered as a new personalized pharmacotherapy strategy.…”