Evolving role of GTP cyclohydrolase 1 inhibition in mitigating cancer pain besides its role in attenuating tumor growth

摘要

The recent article by Pickert et al.1 regarding inhibition of GTP cyclohydrolase to attenuate tumor growth provided for very stimulating reading. Interestingly, recent data suggest that GTP cyclohydrolase 1 (GCH1) plays a significant role in modulating peripheral inflammatory as well as neuropathic pain. Thus, GCH1 may play a significant role in mitigating pain as well as tumor growth in cancer patients. For instance, various polymorphisms of the GCH1 gene have been reported which significantly influence pain ratings in response to exogenous stimuli such as capsaicin. In fact, certain GCH1 haplotypes (rs8007267, rsl0483639 and rs3783641) have been identified that are associated with lower opioid dose requirements as a result of lower 24 hour pain scores.3 As a result, in these haplotypes, there is decreased tetrahydrobiop-terin (BH4) upregulation and attenuated GCH1 levels contributing to higher hypralgesia thresholds. In silico screening for the above three GCH1 genetic variants of the GCH1 gene helps in diagnosis of the pain-protective GCH1 haplotypes with 100% specificity as well as sensitivity.4 The population frequency of these pain protective haplotypes is 15.40%.