Whether it be PeaPure® for pain management or Avandia® for insulin sensitization, PPAR agonists have clear, medical value which might yet be expanded if clinical trials using these agonists to treat conditions from cancer to dementia prove fruitful. PEA in particular has shown unprecedented potential to treat neuropathic pain. The apparent absence of side effects and drug interactions is very promising. Further, researchers and clinicians ought not overlook a treatment that has, even occasionally, proven effective where other therapies failed.
Experimental evidence suggests a connection between the pain ameliorating effects of PPAR agonists and suppression of inflammatory gene expression, including chemokines. In early clinical research, one PPARα agonist, palmitoylethanolamide (PEA), shows promise in relieving chronic pain. If this link can be better established, PPAR agonists may represent a new drug therapy for neuropathic pain.
Evidence from several clinical trials demonstrates that the endogenous PPARα agonist, palmitoylethanolamide (PEA), is an effective treatment for various human pain conditions. PEA was identified in 1957 as a fatty acid amide with anti-inflammatory properties (Kuehl et al., 1957). While PEA is a known agonist of PPARα, its anti-inflammatory effects may be mediated by additional receptors, including the other PPAR isoforms as well as TRPV1 and cannabinoid receptors. Further, PEA appears to have many possible target cells. Additional research is needed to expand our understanding of the mechanisms that underlie PEA’s effects.
PEA is available in some European countries as a dietary supplement for medical purposes under the names een PEA-houdend product® and PeaPure® indicated for the treatment of pain and inflammation. It has demonstrated great efficacy in treating neuropathic pain, even in patients whose pain has proven refractory to other therapies (Biasiotta et al., 2010). Clinical trials have been conducted in patients with diabetic neuropathy (Schifilliti et al., 2014), postoperative pain, sciatic pain, multiple sclerosis pain (Kopsky and Keppel Hesselink, 2012), chemotherapy pain (Truini et al., 2011), and post-stroke pain, among other conditions (Keppel Hesselink (2012) published a detailed review of studies using PEA to treat chronic pain).
Peroxisome proliferator-activated receptor agonists modulate neuropathic pain: a link to chemokines?