Chronic pain presents a widespread and intractable medical problem. While numerous
pharmaceuticals are used to treat
chronic pain, drugs that are safe for extended use and highly effective at treating the most severe
pain do not yet exist.
Chronic pain resulting from
nervous system injury (
neuropathic pain) is common in conditions ranging from
multiple sclerosis to HIV-1
infection to type II diabetes.
Inflammation caused by neuropathy is believed to contribute to the generation and maintenance of
neuropathic pain.
Chemokines are key inflammatory mediators, several of which (MCP-1,
RANTES, MIP-1α,
fractalkine, SDF-1 among others) have been linked to chronic,
neuropathic pain in both human conditions and animal models. The important roles
chemokines play in
inflammation and
pain make them an attractive therapeutic target.
Peroxisome proliferator-activated receptors (PPARs) are a family of
nuclear receptors known for their roles in metabolism. Recent research has revealed that PPARs also play a role in inflammatory gene repression.
PPAR agonists have wide-ranging effects including inhibition of
chemokine expression and
pain behavior reduction in animal models. 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.