Neuropathic pain is a debilitating consequence of CNS injury, MS, and other neurological diseases. Currently, there is no cure for chronic neuropathic pain and most analgesics are ineffective. Interestingly, emerging pre-clinical data indicate that agonists for PPARα and PPARγ attenuate neuropathic pain following peripheral nerve injury (Churi et al., 2008; Maeda et al., 2008; Taylor, 2009; Takahashi et al., 2011; Ruiz-Medina et al., 2012). The anti-inflammatory effects of PPAR activation, occurring through genomic and non-genomic PPAR-dependent mechanisms, may mediate such effects. For example, intrathecal injection of the PPARγ agonists 15d-PGJ2 or rosiglitazone rapidly (<5 min) attenuated pain-like behaviors in rodents; the effects were PPARγ-dependent since co-administering PPARγ antagonists blocked the effects (Churi et al., 2008). It is thought that because actions occur within minutes of drug administration that these analgesic effects must be non-genomic (Fehrenbacher et al., 2009).
