Involvement of Lysophosphatidic Acid in Peripheral Neuropathy and Osteoarthritic Pain in Rats

Abstract

A recent study discovered elevated levels of lysophosphatidic acid (LPA) in the synovial fluid of OA patients (Eli Lilly, unpublished). LPA is required for the initiation of neuropathic pain (Inoue, 2004), and therefore, elevated levels are indicative of a neuropathic pain state. The present study attempted to determine: if 1) LPA causes neuronal damage to joint afferents, and 2) if LPA is responsible for a neuropathic pain component in OA. The experimental OA model monosodium iodoacetate (MIA) was found to cause demyelination to the saphenous nerve at 14 days post-treatment. Selective LPA antagonism prevented this damage, implicating LPA in this novel pain state. The present study concluded that 1) neuropathic pain is a component of OA, and 2) LPA facilitates the initiation of this neuropathic pain. These new findings will allow better understanding of disease etiology and may lead to the emergence of an entirely new line of OA therapeutics.