Above-level mechanical hyperalgesia in rats develops after incomplete spinal cord injury but not after cord transection, and is reversed by amitriptyline, morphine and gabapentin.
Spinal cord injury (SCI) is a major cause of persistent neuropathic pain of central origin. Recent evidence suggests neuropathic pain in clinically complete SCI patients correlates with limited sensory function below the lesion (sensory discomplete). On this basis we examined if the onset of mechanical hyperalgesia was different in rodents after a severe incomplete clip-compression SCI versus a complete spinal cord transection at thoracic segment T13. Above-level withdrawal behaviors evoked by forepaw stimulation provided evidence of mechanical hyperalgesia after incomplete but not complete SCI, whereas below-level responses evoked by hindpaw stimulation revealed hypersensitivity after both injuries. The latency of the above-level response was 4-5 wks but was longer after a moderate clip-compression injury. Mechanical hyperalgesia was fully reversed by three analgesic drugs used in treating neuropathic SCI pain, but their duration of action differed significantly, showing a rank order of amitriptyline (24-48 h)≫morphine (6 h)>gabapentin (2 h). Evidence of central sensitization in cervical spinal cord segments that receive sensory projections from the forelimbs was provided by immunohistochemistry for Zif268, a functional marker of neuroplasticity. Zif268-immunoreactive neurons in laminae I/II increased in response to repetitive noxious forepaw stimulation in the incomplete SCI group, and this response was reduced in the complete transection and sham-operated groups. These data are consistent with the hypothesis that neuropathic pain of cord origin is more likely to develop after SCI when there is an incomplete loss of axons traversing the lesion.
Densmore
Valerie S
VS
Pain Management Research Institute and Kolling Institute of Medical Research, University of Sydney, Level 13 Kolling Building, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Kalous
Adrianna
A
Keast
Janet R
JR
Osborne
Peregrine B
PB
D000588:Amines / Q000627:therapeutic use; D000639:Amitriptyline / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002452:Cell Count; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D004311:Double-Blind Method; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D007839:Functional Laterality; D000077206:Gabapentin; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D017288:Pain Threshold / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000145:classification / Q000150:complications*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D000639:Amitriptyline; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D010751:Phosphopyruvate Hydratase