PPARs and pain

Abstract

Chronic pain is a common cause of disability worldwide and remains a global health and socio-economic challenge. Current analgesics are either ineffective in a significant proportion of patients with chronic pain or associated with significant adverse side effects. The PPARs, a family of nuclear hormone transcription factors, have emerged as important modulators of pain in preclinical studies and therefore a potential therapeutic target for the treatment of pain. Modulation of nociceptive processing by PPARs is likely to involve both transcription-dependent and transcription-independent mechanisms. This review presents a comprehensive overview of preclinical studies investigating the contribution of PPAR signalling to nociceptive processing in animal models of inflammatory and neuropathic pain. We examine current evidence from anatomical, molecular and pharmacological studies demonstrating a role for PPARs in pain control. We also discuss the limited evidence available from relevant clinical studies and identify areas that warrant further research. LINKED ARTICLES: This article is part of a themed section on 8^th European Workshop on Cannabinoid Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.10/issuetoc.

Figure 1

Anatomical localization of PPAR isoforms in key components of the pain pathway and their role in pain modulation. (1) Okine et al. (2014); (2) Okine et al. (2017); (3) Okine et al. (2016); (4) De Novellis et al. (2012); (5) LoVerme et al. (2006); (6) Russo et al. (2007); (7) Hasegawa‐Moriyama et al. (2013); (8) Mansouri et al. (2017a, b); (9) Churi et al. (2008); (10) Griggs et al. (2015); (11) Saito et al. (2016); (12) Hasegawa‐Moriyama et al. (2012); (13) Takahashi et al. (2011); (14) Sagar et al. (2008); (15) D'Agostino et al. (2009); (16) Moreno et al. (2004); (17) Warden et al. (2016); (18) Churi et al. (2008); (19) Maeda et al. (2008); (20) Chakravarthy et al. (2007).