Immunomodulation with Glatiramer Acetate Prevents Long-Term Inflammatory Pain

Abstract

The potential application of glatiramer acetate (GA) therapy as a safe pharmacological treatment for the attenuation or prevention of long-term inflammatory pain in a rat model was explored. Peripheral inflammatory pain was induced by an injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paw. Genome-wide DNA microarray studies were used to survey molecular mechanisms involved in long-term GA analgesic responses. Administration of a single or double subcutaneous injection of GA before, or immediately after, intraplantar injection of pro-inflammatory CFA significantly attenuated allodynia and hyperalgesic pain responses up to ∼3 weeks after CFA treatment. These beneficial effects of GA immunization therapy coincided with the attenuation of expression of the chemotactic fractalkine chemokine (CX3CL1) in the dorsal horn of the lumbar spinal cord (L4-L5) in response to CFA treatment, assessed by DNA microarray and confirmed immunocytochemically (ICC). This study is consistent with the hypothesis that a novel mechanism through which GA immunization therapy may beneficially influence long-term allodynia and hyperalgesia is through central regulation of fractalkine-mediated responses.

Keywords:

• cyclooxygenase
• fractalkine
• glatiramer acetate
• pain