FK506 reduces the severity of cutaneous hypersensitivity in rats with a spinal cord contusion.
Spinal cord injury (SCI) leads to persistent pain as well as motor dysfunction, both of which lack effective therapeutics. The immunosuppressant FK506 (tacrolimus) has been shown to improve behavioral outcome following SCI in rats. Just prior to a mid-thoracic spinal cord contusion injury, rats were injected with either vehicle or FK506 and treatment was continued through the duration of the experiment. Vehicle-treated rats developed significant and long-lasting hind paw hypersensitivity to innocuous mechanical stimulation, noxious heat and cooling stimuli. In contrast, FK506 treatment reduced the duration of both mechanical and cold hypersensitivity. Neither treated groups demonstrated an improvement in locomotor function. Thus, some SCI-induced pain is mediated by an FK506-sensitive mechanism. The data also suggest that motor and sensory dysfunctions resulting from SCI are mediated by distinct mechanisms, requiring the use of multiple therapeutic interventions.
Voda
Jan
J
University of Miami Miller School of Medicine, The Miami Project to Cure Paralysis, 1095 NW 14th Terrace (R-48), Miami, FL 33136, USA.
Hama
Aldric
A
Sagen
Jacqueline
J
D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D013116:Spinal Cord / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications*; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D013904:Thoracic Vertebrae; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016559:Tacrolimus