Restorative effects of stimulating medullary raphe after spinal cord injury.
Serotonin in the spinal cord acutely modulates nociceptive transmission and motor reflexes and may also assist functional restoration after spinal cord injury (SCI). It is released there mainly by descending axons of the medulla's nucleus raphe magnus (NRM). We examined whether mechanical allodynia (cutaneous hypersensitivity) after incomplete SCI is sustainably reversed by prolonged, intermittent electrical stimulation of the NRM and whether altered NRM activity accounts for the allodynia. NRM stimulation was given to rats over several days (average 3.2), beginning about 1 hour after moderate thoracic contusion injury. This stimulation reduced mechanical allodynia in forepaws but not hindpaws at 6 weeks after injury (vs nonstimulated controls). Histologically, the stimulation augmented white matter and reduced astrocytosis (glial fibrillary acidic protein immunostaining) in injured segments at 15 weeks. Cavity volume and perilesion neuron numbers were unchanged. Single-cell extracellular recording 12 to 14 weeks after thoracic contusion injury revealed generally higher spontaneous firing and weaker responses to above-injury noxious stimulation in both inhibited and excited NRM neurons; unresponsive neurons were fewer. Neurons inhibited from dermatomes above the injury were excited from below. Altered NRM activity is unlikely to cause SCI allodynia, since inhibited and excited classes are believed to oppositely modulate nociception. Prolonged, early NRM stimulation probably reverses above-injury allodynia by facilitating qualitative recovery of remaining tissue.
Hentall
Ian D
ID
The Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33101-6960, USA. ihentall@med.miami.edu
Burns
Scott B
SB
D000200:Action Potentials; D000698:Analgesia; D000818:Animals; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D005260:Female; D008297:Male; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement; D011903:Raphe Nuclei / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000534:rehabilitation*