Hyperalgesia in an animal model of multiple sclerosis.
Many individuals with multiple sclerosis (MS) experience clinically significant pain, yet the underlying neural mechanisms for MS pain are not understood. Experimental autoimmune encephalomyelitis (EAE) is a well-studied disease in rodents that mimics many clinical and pathological features of MS, including central nervous system inflammation and demyelination. To determine whether EAE is an appropriate model for MS-related pain, nociceptive responses in both male and female SJL mice were measured before and after immunization with myelin proteolipid protein peptide 139-151 (PLP(139-151)) in complete Freund's adjuvant to induce 'active' EAE. To determine if changes in nociception were due to direct effects of encephalitogenic T cells, nociceptive responses in female SJL mice were measured following the transfer of activated, PLP(139-151) specific T cells to induce 'passive' EAE. Both forepaw and tail withdrawal latencies to a radiant heat stimulus were measured. In both active and passive EAE, there was an initial increase in tail withdrawal latency (hypoalgesia) that peaked several days prior to the peak in motor deficits during the acute disease phase. During the chronic disease phase, tail withdrawal latencies decreased and were significantly faster than control latencies for up to 38 days post-immunization. This hyperalgesia was seen in both sexes and in both active and passive EAE models. Forepaw withdrawal latencies remained within 1-2 s of baseline latencies for the entire testing period, indicating that the hypoalgesia and hyperalgesia were most pronounced in clinically affected body regions. These results suggest that both active and passive EAE are useful models of MS-related pain.
Neurological Sciences Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Sue A
SA
Aicher
Marc B
MB
Silverman
Clayton W
CW
Winkler
Bruce F
BF
Bebo
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*