Immunomodulation with glatiramer acetate prevents long-term inflammatory pain.
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 approximately 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.
Sharma
Naresh
N
Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029, USA.
Thomas
Sunil
S
Ho
Lap
L
Reyes
Dillenia C
DC
Sacerdote
Paola
P
Bianchi
Mauro
M
Pasinetti
Giulio Maria
GM
D000818:Animals; D054428:Chemokine CX3CL1 / Q000187:drug effects*; D000068717:Glatiramer Acetate; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications*; D007267:Injections; D008297:Male; D010146:Pain / Q000209:etiology* / Q000517:prevention & control*; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D054428:Chemokine CX3CL1; D007155:Immunologic Factors; D010455:Peptides; D000068717:Glatiramer Acetate